DyslipidaemiasPhase 2NCT01218204

A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Administering Multiple Oral Doses of GSK1292263 Alone and With Atorvastatin

A Phase 2 study testing 10mg atorvastatin, 80mg atorvastatin and 100mg GSK1292263 in people with Dyslipidaemias and Dyslipidemias, run by GlaxoSmithKline at 21 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study investigates the safety, pharmacokinetics and effects of GSK1292263 when taken alone or when co-dosed with atorvastatin to subjects with dyslipidemia. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Dyslipidaemias, Dyslipidemias
What is being tested?: 10mg atorvastatin, 80mg atorvastatin and 100mg GSK1292263
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 287 participants
Where: 21 sitesUnited States
Study dates: 14 Sep 2010to 29 Jun 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Healthy adult males and females of non-child-bearing-potential, aged 18-75 years who is capable of giving informed consent.
A female subject is eligible to participate if she is of:
Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea. In questionable cases, a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol <40 pg/ml (<140 pmol/L) is confirmatory in the absence of a clear post-menopausal history.
Females on hormone replacement therapy (HRT) must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study.
Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until seven days following the last dose.
Body weight > 50 kg (110 pounds) and body mass index (BMI) between 19.0 and 39.0 (inclusive).

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Part A: (i) Subjects who are on 80mg or 40mg atorvastatin for >= 4 weeks and are tolerating the drug well, or (ii) Subjects not on lipid-modifying therapy who have a fasting low density lipoprotein cholesterol (LDLc) >= 130mg/dL.
In Part B at Screening: Subjects who are on statins or Vytorin treatment for >= 4 weeks.
Part B at the end of the 4 week washout: Subjects who have a fasting LDL cholesterol of >=120mg/dL and <=180mg/dL and fasting triglycerides of >=100mg/dL and <=400mg/dL.
Part B at the end of the 4 week run-in on atorvastatin: Subjects who are tolerating well atorvastatin 10mg or 80mg (as determined by the Investigator).
Part B: Subjects must be willing to discontinue statins or Vytorin for the duration of the study.
Liver enzymes, AST and ALT < 2x upper limit of normal (ULN); alkaline phosphatase and bilirubin =< 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). Subjects with Gilbert's syndrome are allowed to participate in the study.
Average QTcB or QTcF < 450msec; or QTc < 480msec in subjects with right bundle branch block.

Who cannot join

A medical history of the following:
Clinical or angiographic cardiovascular disease, including history or current evidence of coronary heart disease, heart failure, cerebrovascular disease (including stroke and transient ischemic attack [mini-stroke]), peripheral vascular disease. Subjects pending diagnostic procedures for any of those conditions at the time of screening will not be eligible for participation.
Homozygous familial hypercholesterolemia or family history of familial hypercholesterolemia (Part B only). Note: Subjects with heterozygous familial hypercholesterolemia on 80mg atorvastatin who are tolerating this drug well and fulfill the other eligibility criteria may participate in Part A only.
History of recurrent or unexplained muscle aches (e.g., fibromyalgia), myopathy or myositis, whether or not it is related to treatment with statins or other lipid modifying drugs.
Renal impairment as defined by a calculated glomerular filtration rate < 60 mL/min
History of diabetes mellitus, or history of post-prandial and/or random blood glucose > 200 mg/dl or fasting glucose > 125 mg/dL or currently taking diabetes medications to manage fasting glucose levels (e.g., thiazolidinediones, sulfonylureas, insulin, metformin).

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History of pancreatitis within 10 years of screening.
Any concurrent serious illness (e.g., severe chronic obstructive pulmonary disease, sleep apnea, history of malignancy other than skin cancer within 5 years of initial diagnosis or with evidence of recurrence) that may interfere with a subject from completing the study.
Current or chronic history of liver disease, or known hepatic or biliary abnormalities.
Active peptic ulcer disease and/or history of peptic ulcer disease or gastrointestinal bleeding within 12 months prior to screening.
History of kidney stones within 10 years of screening.
History of uncorrected thyroid dysfunction or an abnormal thyroid function test assessed by thyroid stimulating hormone (TSH) at Screening. (NOTE: subjects with hypothyroidism on a stable dose of thyroid replacement therapy for at least 3 months prior to screening and who have a screening TSH within the normal range may participate.)
Symptomatic cholelithiasis or obstructive or inflammatory gallbladder disease within 3 months prior to screening.
Gastrointestinal disease that could affect fat or bile acid absorption, or the pharmacokinetics or pharmacodynamics of the study drugs, including inflammatory bowel disease, chronic diarrhea, Crohn's disease or malabsorption syndromes within the past year.
Gastrointestinal surgery that may affect the pharmacokinetics or pharmacodynamics of the study drugs.
Note: Subjects may be enrolled in the study if they have had a cholecystectomy three or more months before the time of screening and are stable and asymptomatic.
Subjects taking ezetimibe monotherapy, fibrates, bile acid binding resins, nicotinic acid or fat absorption inhibitors are not eligible for Parts A and B.
For females a hemoglobin < 11.5g/dL, and for males a hemoglobin < 12.5g/dL.
Current inadequately controlled hypertension (blood pressure >= 160mmHg systolic or >= 100mmHg diastolic at screening). If blood pressure medication is changed as a result of screening, blood pressure will be re-measured after 6 weeks and must again meet these criteria.
Significant electrocardiogram (ECG) abnormalities, defined as follows:
Heart Rate < 50 and >100bpm PR Interval <120 and > 220ms QRS duration < 70 and >120ms QTC Interval (Bazett) > 450ms Or, has clinically significant rhythm abnormalities identified during 24-hour screening Holter assessment. Subjects with left bundle branch block are excluded from the study. Subjects with partial right bundle branch block may be considered for inclusion following consultation with the GlaxoSmithKline (GSK) Medical Monitor. Subjects with Wolf-Parkinson-White (WPW) syndrome are excluded from the study.
Creatinine phosphokinase (CPK) >= 2x ULN at screening.
A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
A positive test for HIV antibody.
The subject has a positive pre-study drug-of-abuse screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks/week for men or >7 drinks/week for women. One drink is equivalent to (12 g alcohol) = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits.
Subjects will be excluded if they require treatment with systemic corticosteroids.
Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to dosing.
Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
History of sensitivity or untoward reaction to the study medications (GSK1292263, atorvastatin or ezetimibe), or components thereof or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation.
History of intolerance to statins.
Any change in concomitant medication (including multivitamins, herbal remedies, dietary supplements, and over-the-counter medication) within six weeks prior to screening that is not approved by GSK.
On a diet that may affect study outcomes, or any change in diet, exercise habits or smoking status within six weeks prior to screening or planned change during study (e.g., new exercise program) other than that in the dietary instructions in the Study Procedures Manual.
Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
Where participation in study would result in donation of blood in excess of approximately 500mL within a 56 day period.
Subject is mentally or legally incapacitated.
Unwillingness or inability to follow the procedures outlined in the protocol.
Pregnant females as determined by positive urine hCG test at screening or prior to dosing.
Lactating females.
History of sensitivity to heparin or heparin-induced thrombocytopenia.
Consumption of red wine, Seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
Unwilling to abstain from caffeine-or xanthine-containing products from Day -2 until Day 15.
Subject is either an immediate family member of a participating investigator, study coordinator, employee of an investigator; or is a member of the staff conducting the study.

Trial locations and contacts

21 sites in 1 country.

City, postcode or hospital

21 sites in 1 country

United States21 sites

GSK Investigational Site
Anniston, Alabama, 36207
GSK Investigational Site
Berlin, New Jersey, 08009
GSK Investigational Site
Chicago, Illinois, 60607
GSK Investigational Site
Chicago, Illinois, 60610
GSK Investigational Site
Chula Vista, California, 91910
GSK Investigational Site
Cincinnati, Ohio, 45246
GSK Investigational Site
Eugene, Oregon, 97404
GSK Investigational Site
Jacksonville, Florida, 32216
GSK Investigational Site
Kalamazoo, Michigan, 49007
GSK Investigational Site
Louisville, Kentucky, 40213
GSK Investigational Site
Miami, Florida, 33169
GSK Investigational Site
Miami, Florida, 33183
GSK Investigational Site
Minneapolis, Minnesota, 55430
GSK Investigational Site
Oklahoma City, Oklahoma, 73112
GSK Investigational Site
Port Orange, Florida, 32127
GSK Investigational Site
Renton, Washington, 98057
GSK Investigational Site
San Antonio, Texas, 78205
GSK Investigational Site
San Antonio, Texas, 78229
GSK Investigational Site
Spartanburg, South Carolina, 29303
GSK Investigational Site
St. Petersburg, Florida, 33709
GSK Investigational Site
Stockton, California, 95204

Other trials in United States

About this study

This study investigates the safety, pharmacokinetics and effects of GSK1292263 when taken alone or when co-dosed with atorvastatin to subjects with dyslipidemia.

Read the detailed description

This compound has been studied in healthy subjects and subjects with type II diabetes and is now being studied in subjects with dyslipidemia. Because many patients with dyslipidemia are on statins, it is important to study how GSK1292263 behaves when taken with a potent statin, atorvastatin. The cholesterol lowering drug, ezetimibe, is included for comparison.

Conditions: Dyslipidaemias, Dyslipidemias
Being tested: 10mg atorvastatin, 80mg atorvastatin, GSK1292263 Placebo, 100mg GSK1292263, 300mg GSK1292263
Keywords: Pharmacodynamics, Lipids, Dyslipidemia, Safety, GSK1292263, Ezetimibe, Statin, Pharmacokinetics, Tolerability, Atorvastatin
Medical subject headings: Dyslipidemias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

10mg atorvastatinDrug
Also called Lipitor
10mg
80mg atorvastatinDrug
Also called Lipitor
80mg
GSK1292263 PlaceboDrug
Placebo
100mg GSK1292263Drug
100mg
300mg GSK1292263Drug
300mg
800mg GSK1292263Drug
800mg
10mg ezetimibeDrug
Also called Zetia
10mg
WashoutOther
No interventions - washout period

Study groups in NCT01218204
Study group	Role	What they receive
Part A Run-in	Other	Subjects on stable 40mg atorvastatin > 4 weeks may raise their dose to 80mg for 2 weeks in order to qualify for Part A. Receives: Drug: 80mg atorvastatin
Part A Co-Dosing 800mg GSK1292263	Experimental	Dosing for 14 days Receives: Drug: 800mg GSK1292263
Part B Washout	Other	Washout for 4 weeks Receives: Other: Washout
Part B Run-in 10mg atorvastatin	Active comparator	Dosing for 4 weeks Receives: Drug: 10mg atorvastatin
Part B Run-in 80mg atorvastatin	Active comparator	Dosing for 4 weeks Receives: Drug: 80mg atorvastatin
Part B Co-Dosing 10mg atorvastatin + 100mg GSK1292263	Experimental	Dosing for 14 days Receives: Drug: 10mg atorvastatin
Part B Co-Dosing 10mg atorvastatin + 300mg GSK1292263	Experimental	Dosing for 14 days Receives: Drug: 300mg GSK1292263
Part B Co-Dosing 10mg atorvastatin + 800mg GSK1292263	Experimental	Dosing for 14 days Receives: Drug: 10mg atorvastatin; Drug: 800mg GSK1292263
Part B Co-Dosing 10mg atorvastatin + 10mg ezetimibe	Experimental	Dosing for 14 days Receives: Drug: 10mg atorvastatin; Drug: 10mg ezetimibe
Part B Dosing 100mg GSK1292263	Experimental	Dosing for 14 days Receives: Drug: 100mg GSK1292263
Part B Dosing 300mg GSK1292263	Experimental	Dosing for 14 days Receives: Drug: 300mg GSK1292263
Part B Dosing 800mg GSK1292263	Experimental	Dosing for 14 days Receives: Drug: 800mg GSK1292263
Part B Dosing Placebo GSK1292263	Experimental	Dosing for 14 days Receives: Drug: GSK1292263 Placebo
Part B Co-Dosing 80mg atorvastatin + 800mg GSK1292263	Experimental	Dosing for 14 days Receives: Drug: 80mg atorvastatin
Part B Co-dosing 80mg atorvastatin + Placebo (GSK1292263)	Experimental	Dosing for 14 days Receives: Drug: GSK1292263 Placebo
Part B Co-Dosing 10mg atorvastatin + Placebo (GSK1292263)	Experimental	Dosing for 14 days Receives: Drug: 10mg atorvastatin

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)- Part A
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Measured: Up to Day 26
Number of Participants With Any AEs and SAEs- Part B (Washout)
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Measured: Up to Day 28
Number of Participants With Any AEs and SAEs- Part B (Run-in)
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Measured: Up to Day 28
Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm)
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Measured: Up to Day 26
Number of Participants With Abnormal- Clinically Significant Electrocardiogram (ECG) Findings- Part A
Single ECGs were taken after admission on Day -1 and at Follow-up (up to Day 26). On Days 1, 7, and 14 single ECGS were taken pre-breakfast (fasting) and at 1, 3, 6, 8, 14 and 24 hours post-dose. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. No value found to be abnormal clinically significant in Part A of the study.
Measured: Up to Day 26
Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Washout)
ECGs were taken at Screening, and on Day1 and Day 28. Single assessments were made. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings.
Measured: Up to Day 28
Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Run-in)
ECGs were taken on Day 28. Single assessments were made. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. No data found to be abnormal clinically significant in run-in phase.
Measured: Day 28
Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Pooled Treatment Arm)
Single ECGs were taken after admission on Day -2, and pre-breakfast on Days -1, 4, 10, and at Follow-up. On Days 1, 7, and 14 single ECGS were taken pre-breakfast (fasting) and at 1, 3, 6, 8, 14 and 24 hours post-dose. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. The data was found to be abnormal clinically significant in treatment phase.
Measured: Up to Day 26
Number of Participants With Vital Signs of Potential Clinical Importance (PCI)- Part A
Assessment of vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate was performed after admission on Day -1 and at Follow-up. On Days 1, 7 and 14, they were taken at pre-dose, 1, 3, 6, 8, 14 and 24 hours after the morning dose. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.
Measured: Up to Day 26
Number of Participants With Vital Signs of PCI- Part B (Washout)
Assessment of vital signs including SBP, DBP heart rate was performed at Screening, on Days 1, 14 and 28 in the morning. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.
Measured: Up to day 28
Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Run-in)
Assessment of vital signs including SBP, DBP and heart rate was performed on Days 1, 14 and 28 in the morning. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.
Measured: Up to day 28
Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm)
Assessment of vital signs including SBP, DBP and heart rate was performed after admission on Day-2, and pre-breakfast on Days -1, 4, and 10 in a fasting state early in the morning (prior to dosing), and at Follow-up. On Days 1, 7 and 14, they were also be taken at 1, 3, 6, 9, 12 and 24 hours after the morning dose. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.
Measured: Up to Day 26
Number of Participants With Abnormal Hematology Value of PCI- Part A
Blood samples were collected fasting on Day -1, and prior to breakfast (early in the morning, fasting) on Days 2, 4, 7, 11 and on Day 15 prior to checkout (24 hours post last-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Data for only those parameters (Hematocrit, Hemoglobin and Total neutrophils) are presented for which findings are of PCI either high or low.
Measured: Up to Day 26
Number of Participants With Abnormal Hematology Value of PCI- Part B (Washout)
Blood samples were collected at screening, and on Days 1 (first day of washout), 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (White blood cells [WBC], Total neutrophils, Hematocrit and Lymphocytes) are presented for which findings are of PCI either high or low.
Measured: Up to Day 28
Number of Participants With Abnormal Hematology Value of PCI- Part B (Run-in)
Blood samples were collected on Day 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Lymphocytes) are presented for which findings are of PCI either high or low.
Measured: Days 14 and 28
Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm)
Blood samples were collected fasting on Day -2, and prior to breakfast (early in the morning, fasting) on Days 2 (pre-dose), 4, 7, 10, 13 and on Day 15 prior to checkout (24hrs post-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24hrs post dose = pre-dose (time 0) for the next dose). Data for only those parameters (Platelet count, Total neutrophils and Lymphocytes) are presented for which findings are of PCI either high or low.
Measured: Up to Day 26
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part A
Samples were collected fasting on Day -1, and prior to breakfast (early in the morning, fasting) on Days 2, 4, 7, 11 and on Day 15 prior to checkout (24 hours post last-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). No parameter was found to have any value of PCI.
Measured: Up to Day 26
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout)
Samples were collected at screening, and on Days1 (first day of washout), 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Inorganic phosphorus, Sodium, Alanine aminotransferase [ALT], Potassium, Creatinine, Calcium, magnesium, Glucose, Total Bilirubin, Carbon dioxide/bicarbonate [CO2/HCO3] and Aspartate aminotransferase [AST]) are presented for which findings are of PCI either high or low.
Measured: Up to Day 28
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in)
Samples were collected on Day 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Glucose, Magnesium, ALT, AST, Calcium, Inorganic phosphorus and Total bilirubin) are presented for which findings are of PCI either high or low.
Measured: Days 14 and 28
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm)
Samples were collected fasting on Day -2, and prior to breakfast (early in the morning, fasting) on Days 2 (pre-dose), 4, 7, 10, 13 and on Day 15 prior to checkout (24 hours post-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post dose = pre-dose (time 0) for the next dose). Data for only those parameters (Glucose, Total bilirubin, Albumin, Magnesium, CO2/HCO3, Calcium, ALT, AST, Inorganic phosphorus, Potassium and Sodium) are presented for which findings are of PCI either high or low.
Measured: Up to Day 26
Maximum Observed Concentration (Cmax) of GSK1292263- Part A
Serial blood samples for the determination of the PK for GSK1292263 on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1).
Measured: On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Cmax of GSK1292263- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16).
Measured: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Time of Occurrence of Cmax (Tmax) and Terminal Phase Half-life (t1/2) GSK1292263- Part A
Serial blood samples for the determination of the PK for GSK1292263, on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1).
Measured: On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) of GSK1292263- Part A
Serial blood samples for the determination of the PK for GSK1292263 on Days 1 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48h sample on Day 1).
Measured: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16).
Measured: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Tlag of GSK1292263- Part B (Pooled Treatment Arm)
Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose.
Measured: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose.
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours [AUC(0-24)] of GSK1292263- Part A
Serial blood samples for the determination of the PK for GSK1292263, on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1).
Measured: On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16).
Measured: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Trough Concentration of GSK1292263
Trough samples for GSK1292263 PK (all treatment arms) were planned to be collected early in the morning on Days 13, 14, 15 and 16 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48h PK sample was collected on Day 16). (pre-dose for Days 13 and 14; trough Day 15 = 24h post last dose; trough Day 16 = 48h post last dose).
Measured: On Days 13, 14, 15 and 16 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Cmax of Atorvastatin- Part A
Serial blood samples for the determination of the PK for atorvastatin on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
Measured: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
Cmax of Atorvastatin- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
Measured: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Tmax of Atorvastatin- Part A
Serial blood samples for the determination of the PK for atorvastatin on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
Measured: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
Tmax of Atorvastatin- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
Measured: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
AUC (0-24) of Atorvastatin- Part A
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
Measured: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
Measured: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Trough Concentration of Atorvastatin
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were planned to be collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were planned to be collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were planned to be collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was planned to be collected on Day 16).
Measured: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
Measured: Baseline and Day 14
Percent Change From Baseline in Lipid Metabolism: Apolipoprotein E at Day 14 (24 Hours)
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
Measured: Baseline and Day 14
Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours)
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
Measured: Baseline and Day 14
Percent Change From Baseline in Lipid Metabolism: LDL/HDL Ratio at Day 14 (24 Hours)
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
Measured: Baseline and Day 14
Weighted Mean Area Under Concentration Curve From 0 to 24 Hours (AUC [0-24]) Change From Baseline for Triglycerides at Day 14
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was Day -1 value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
Measured: Baseline and Day 14

Secondary outcomes (7)

Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A
Serial blood samples for the determination of the PK for atorvastatin metabolites on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin metabolites on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
Measured: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
Measured: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A
Serial blood samples for the determination of the PK for atorvastatin metabolites on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin metabolites on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
Measured: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
Measured: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose and on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A
Serial blood samples for the determination of the PK for atorvastatin metabolites on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin metabolites on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
Measured: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
Measured: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Trough Concentration of Atorvastatin Metabolite (2-Hydroxyatorvastatin)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were supposed to collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were supposed to collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were supposed to collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16). However no data was collected.
Measured: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Sep 201029 Jun 2011

First posted11 Oct 2010 (estimated)
Study start14 Sep 2010
Primary completion29 Jun 2011
Study completion29 Jun 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for DyslipidaemiasStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 287 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01218204
Sponsor's protocol ID: 113779
Status last verified: Jun 2019
First submitted: 23 Sep 2010
Last updated: 16 Jul 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: IPD for this study will be made available via the Clinical Study Data Request site.

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See locations

Not yet recruiting
Improved Medication and Care to Achieve Lipid Targets After Carotid Surgery
Dyslipidaemias, Carotid Artery Stenoses
RecruitingObservational study
Assessment of Compliance With European and French Guidelines for the Management of Dyslipidaemias
Patient With Dyslipidemia

All Dyslipidaemias trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Administering Multiple Oral Doses of GSK1292263 Alone and With Atorvastatin
ClinicalTrials.gov ID: NCT01218204
Acronym / sponsor ID: 113779
Conditions: Dyslipidaemias, Dyslipidemias
Keywords: Pharmacodynamics, Lipids, Dyslipidemia, Safety, GSK1292263, Ezetimibe, Statin, Pharmacokinetics
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 287 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 14 Sep 2010 (actual)
Primary completion: 29 Jun 2011 (actual)
Study completion: 29 Jun 2011 (actual)
First posted: 11 Oct 2010 (estimated)
Results: Posted 8 Nov 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study investigates the safety, pharmacokinetics and effects of GSK1292263 when taken alone or when co-dosed with atorvastatin to subjects with dyslipidemia.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 16

Arm	Type	Receives
Part A Run-in	Other	Drug: 80mg atorvastatinSubjects on stable 40mg atorvastatin > 4 weeks may raise their dose to 80mg for 2 weeks in order to qualify for Part A.
Part A Co-Dosing 800mg GSK1292263	Experimental	Drug: 800mg GSK1292263Dosing for 14 days
Part B Washout	Other	Other: WashoutWashout for 4 weeks
Part B Run-in 10mg atorvastatin	Active comparator	Drug: 10mg atorvastatinDosing for 4 weeks
Part B Run-in 80mg atorvastatin	Active comparator	Drug: 80mg atorvastatinDosing for 4 weeks
Part B Co-Dosing 10mg atorvastatin + 100mg GSK1292263	Experimental	Drug: 10mg atorvastatinDosing for 14 days
Part B Co-Dosing 10mg atorvastatin + 300mg GSK1292263	Experimental	Drug: 300mg GSK1292263Dosing for 14 days
Part B Co-Dosing 10mg atorvastatin + 800mg GSK1292263	Experimental	Drug: 10mg atorvastatin, Drug: 800mg GSK1292263Dosing for 14 days
Part B Co-Dosing 10mg atorvastatin + 10mg ezetimibe	Experimental	Drug: 10mg atorvastatin, Drug: 10mg ezetimibeDosing for 14 days
Part B Dosing 100mg GSK1292263	Experimental	Drug: 100mg GSK1292263Dosing for 14 days
Part B Dosing 300mg GSK1292263	Experimental	Drug: 300mg GSK1292263Dosing for 14 days
Part B Dosing 800mg GSK1292263	Experimental	Drug: 800mg GSK1292263Dosing for 14 days
Part B Dosing Placebo GSK1292263	Experimental	Drug: GSK1292263 PlaceboDosing for 14 days
Part B Co-Dosing 80mg atorvastatin + 800mg GSK1292263	Experimental	Drug: 80mg atorvastatinDosing for 14 days
Part B Co-dosing 80mg atorvastatin + Placebo (GSK1292263)	Experimental	Drug: GSK1292263 PlaceboDosing for 14 days
Part B Co-Dosing 10mg atorvastatin + Placebo (GSK1292263)	Experimental	Drug: 10mg atorvastatinDosing for 14 days

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

Healthy adult males and females of non-child-bearing-potential, aged 18-75 years who is capable of giving informed consent.
A female subject is eligible to participate if she is of:
Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until seven days following the last dose.
Body weight > 50 kg (110 pounds) and body mass index (BMI) between 19.0 and 39.0 (inclusive).
Part A: (i) Subjects who are on 80mg or 40mg atorvastatin for >= 4 weeks and are tolerating the drug well, or (ii) Subjects not on lipid-modifying therapy who have a fasting low density lipoprotein cholesterol (LDLc) >= 130mg/dL.

Key exclusion criteria (43 listed)

A medical history of the following:
Note: Subjects may be enrolled in the study if they have had a cholecystectomy three or more months before the time of screening and are stable and asymptomatic.
Subjects taking ezetimibe monotherapy, fibrates, bile acid binding resins, nicotinic acid or fat absorption inhibitors are not eligible for Parts A and B.
For females a hemoglobin < 11.5g/dL, and for males a hemoglobin < 12.5g/dL.
Current inadequately controlled hypertension (blood pressure >= 160mmHg systolic or >= 100mmHg diastolic at screening). If blood pressure medication is changed as a result of screening, blood pressure will be re-measured after 6 weeks and must again meet these criteria.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
10mg atorvastatinAlso: Lipitor10mg	Drug	Part B Co-Dosing 10mg atorvastatin + 100mg GSK1292263, Part B Co-Dosing 10mg atorvastatin + 10mg ezetimibe, Part B Co-Dosing 10mg atorvastatin + 800mg GSK1292263, Part B Co-Dosing 10mg atorvastatin + Placebo (GSK1292263), Part B Run-in 10mg atorvastatin
80mg atorvastatinAlso: Lipitor80mg	Drug	Part A Run-in, Part B Co-Dosing 80mg atorvastatin + 800mg GSK1292263, Part B Run-in 80mg atorvastatin
GSK1292263 PlaceboPlacebo	Drug	Part B Co-dosing 80mg atorvastatin + Placebo (GSK1292263), Part B Dosing Placebo GSK1292263
100mg GSK1292263100mg	Drug	Part B Dosing 100mg GSK1292263
300mg GSK1292263300mg	Drug	Part B Co-Dosing 10mg atorvastatin + 300mg GSK1292263, Part B Dosing 300mg GSK1292263
800mg GSK1292263800mg	Drug	Part A Co-Dosing 800mg GSK1292263, Part B Co-Dosing 10mg atorvastatin + 800mg GSK1292263, Part B Dosing 800mg GSK1292263
10mg ezetimibeAlso: Zetia10mg	Drug	Part B Co-Dosing 10mg atorvastatin + 10mg ezetimibe
WashoutNo interventions - washout period	Other	Part B Washout

Primary outcome

Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)- Part A
Time frame: Up to Day 26
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Number of Participants With Any AEs and SAEs- Part B (Washout)
Time frame: Up to Day 28
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Number of Participants With Any AEs and SAEs- Part B (Run-in)
Time frame: Up to Day 28
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm)
Time frame: Up to Day 26
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Number of Participants With Abnormal- Clinically Significant Electrocardiogram (ECG) Findings- Part A
Time frame: Up to Day 26
Single ECGs were taken after admission on Day -1 and at Follow-up (up to Day 26). On Days 1, 7, and 14 single ECGS were taken pre-breakfast (fasting) and at 1, 3, 6, 8, 14 and 24 hours post-dose. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. No value found to be abnormal clinically significant in Part A of the study.
Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Washout)
Time frame: Up to Day 28
ECGs were taken at Screening, and on Day1 and Day 28. Single assessments were made. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings.
Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Run-in)
Time frame: Day 28
ECGs were taken on Day 28. Single assessments were made. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. No data found to be abnormal clinically significant in run-in phase.
Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Pooled Treatment Arm)
Time frame: Up to Day 26
Single ECGs were taken after admission on Day -2, and pre-breakfast on Days -1, 4, 10, and at Follow-up. On Days 1, 7, and 14 single ECGS were taken pre-breakfast (fasting) and at 1, 3, 6, 8, 14 and 24 hours post-dose. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. The data was found to be abnormal clinically significant in treatment phase.
Number of Participants With Vital Signs of Potential Clinical Importance (PCI)- Part A
Time frame: Up to Day 26
Assessment of vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate was performed after admission on Day -1 and at Follow-up. On Days 1, 7 and 14, they were taken at pre-dose, 1, 3, 6, 8, 14 and 24 hours after the morning dose. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.
Number of Participants With Vital Signs of PCI- Part B (Washout)
Time frame: Up to day 28
Assessment of vital signs including SBP, DBP heart rate was performed at Screening, on Days 1, 14 and 28 in the morning. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.
Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Run-in)
Time frame: Up to day 28
Assessment of vital signs including SBP, DBP and heart rate was performed on Days 1, 14 and 28 in the morning. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.
Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm)
Time frame: Up to Day 26
Assessment of vital signs including SBP, DBP and heart rate was performed after admission on Day-2, and pre-breakfast on Days -1, 4, and 10 in a fasting state early in the morning (prior to dosing), and at Follow-up. On Days 1, 7 and 14, they were also be taken at 1, 3, 6, 9, 12 and 24 hours after the morning dose. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.
Number of Participants With Abnormal Hematology Value of PCI- Part A
Time frame: Up to Day 26
Blood samples were collected fasting on Day -1, and prior to breakfast (early in the morning, fasting) on Days 2, 4, 7, 11 and on Day 15 prior to checkout (24 hours post last-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Data for only those parameters (Hematocrit, Hemoglobin and Total neutrophils) are presented for which findings are of PCI either high or low.
Number of Participants With Abnormal Hematology Value of PCI- Part B (Washout)
Time frame: Up to Day 28
Blood samples were collected at screening, and on Days 1 (first day of washout), 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (White blood cells [WBC], Total neutrophils, Hematocrit and Lymphocytes) are presented for which findings are of PCI either high or low.
Number of Participants With Abnormal Hematology Value of PCI- Part B (Run-in)
Time frame: Days 14 and 28
Blood samples were collected on Day 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Lymphocytes) are presented for which findings are of PCI either high or low.
Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm)
Time frame: Up to Day 26
Blood samples were collected fasting on Day -2, and prior to breakfast (early in the morning, fasting) on Days 2 (pre-dose), 4, 7, 10, 13 and on Day 15 prior to checkout (24hrs post-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24hrs post dose = pre-dose (time 0) for the next dose). Data for only those parameters (Platelet count, Total neutrophils and Lymphocytes) are presented for which findings are of PCI either high or low.
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part A
Time frame: Up to Day 26
Samples were collected fasting on Day -1, and prior to breakfast (early in the morning, fasting) on Days 2, 4, 7, 11 and on Day 15 prior to checkout (24 hours post last-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). No parameter was found to have any value of PCI.
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout)
Time frame: Up to Day 28
Samples were collected at screening, and on Days1 (first day of washout), 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Inorganic phosphorus, Sodium, Alanine aminotransferase [ALT], Potassium, Creatinine, Calcium, magnesium, Glucose, Total Bilirubin, Carbon dioxide/bicarbonate [CO2/HCO3] and Aspartate aminotransferase [AST]) are presented for which findings are of PCI either high or low.
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in)
Time frame: Days 14 and 28
Samples were collected on Day 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Glucose, Magnesium, ALT, AST, Calcium, Inorganic phosphorus and Total bilirubin) are presented for which findings are of PCI either high or low.
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm)
Time frame: Up to Day 26
Samples were collected fasting on Day -2, and prior to breakfast (early in the morning, fasting) on Days 2 (pre-dose), 4, 7, 10, 13 and on Day 15 prior to checkout (24 hours post-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post dose = pre-dose (time 0) for the next dose). Data for only those parameters (Glucose, Total bilirubin, Albumin, Magnesium, CO2/HCO3, Calcium, ALT, AST, Inorganic phosphorus, Potassium and Sodium) are presented for which findings are of PCI either high or low.
Maximum Observed Concentration (Cmax) of GSK1292263- Part A
Time frame: On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Serial blood samples for the determination of the PK for GSK1292263 on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1).
Cmax of GSK1292263- Part B (Pooled Treatment Arm)
Time frame: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16).
Time of Occurrence of Cmax (Tmax) and Terminal Phase Half-life (t1/2) GSK1292263- Part A
Time frame: On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Serial blood samples for the determination of the PK for GSK1292263, on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1).
Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) of GSK1292263- Part A
Time frame: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Serial blood samples for the determination of the PK for GSK1292263 on Days 1 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48h sample on Day 1).
Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm)
Time frame: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16).
Tlag of GSK1292263- Part B (Pooled Treatment Arm)
Time frame: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose.
Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose.
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours [AUC(0-24)] of GSK1292263- Part A
Time frame: On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Serial blood samples for the determination of the PK for GSK1292263, on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1).
AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm)
Time frame: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16).
Trough Concentration of GSK1292263
Time frame: On Days 13, 14, 15 and 16 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Trough samples for GSK1292263 PK (all treatment arms) were planned to be collected early in the morning on Days 13, 14, 15 and 16 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48h PK sample was collected on Day 16). (pre-dose for Days 13 and 14; trough Day 15 = 24h post last dose; trough Day 16 = 48h post last dose).
Cmax of Atorvastatin- Part A
Time frame: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
Serial blood samples for the determination of the PK for atorvastatin on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
Cmax of Atorvastatin- Part B (Pooled Treatment Arm)
Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
Tmax of Atorvastatin- Part A
Time frame: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
Serial blood samples for the determination of the PK for atorvastatin on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
Tmax of Atorvastatin- Part B (Pooled Treatment Arm)
Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
AUC (0-24) of Atorvastatin- Part A
Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm)
Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
Trough Concentration of Atorvastatin
Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were planned to be collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were planned to be collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were planned to be collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was planned to be collected on Day 16).
Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14
Time frame: Baseline and Day 14
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
Percent Change From Baseline in Lipid Metabolism: Apolipoprotein E at Day 14 (24 Hours)
Time frame: Baseline and Day 14
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours)
Time frame: Baseline and Day 14
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
Percent Change From Baseline in Lipid Metabolism: LDL/HDL Ratio at Day 14 (24 Hours)
Time frame: Baseline and Day 14
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
Weighted Mean Area Under Concentration Curve From 0 to 24 Hours (AUC [0-24]) Change From Baseline for Triglycerides at Day 14
Time frame: Baseline and Day 14
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was Day -1 value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.

7 secondary outcomes

Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A
Time frame: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm)
Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A
Time frame: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm)
Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose and on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A
Time frame: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm)
Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Trough Concentration of Atorvastatin Metabolite (2-Hydroxyatorvastatin)
Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose

Results and safety

Results posted to the registry on 8 Nov 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A	6	6
Part B Washout	0	0
Part B Run-in	0	0
Part B Pooled Treatment Arm	0	0

Primary outcome: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)- Part A

Time frame: Up to Day 26. Count of participants. Unit: Participants

Measure	80 mg Atorvastatin + 800 mg GSK1292263 n = 4	800 mg GSK1292263 n = 2
Any AE	0	2
Any SAE	0	0

Population analysed: Safety Population consisted of all participants who received at least one dose of study medication.

Primary outcome: Number of Participants With Any AEs and SAEs- Part B (Washout)

Time frame: Up to Day 28. Count of participants. Unit: Participants

Measure	Pre-treatment n = 281	Washout n = 281
Any AE	14	37
Any SAE	0	0

Population analysed: All subject Population consisted of all participants who received at least one dose of study medication.

Primary outcome: Number of Participants With Any AEs and SAEs- Part B (Run-in)

Time frame: Up to Day 28. Count of participants. Unit: Participants

Measure	Atorvastatin 10 mg n = 62	Atorvastatin 80 mg n = 27
Any AE	19	8
Any SAE	0	0

Population analysed: All subject Population

Primary outcome: Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm)

Time frame: Up to Day 26. Count of participants. Unit: Participants

Measure	Atorvastatin 10 mg + GSK1292263 100 mg n = 11	Atorvastatin 10 mg + GSK1292263 300 mg n = 11	Atorvastatin 10 mg + GSK1292263 800 mg n = 11	Atorvastatin 10 mg + Placebo n = 12	Atorvastatin 10 mg + Ezetimibe 10 mg n = 13	Atorvastatin 80 mg + GSK1292263 800 mg n = 12	Atorvastatin 80 mg + Placebo n = 13	GSK1292263 100 mg n = 11	GSK1292263 300 mg n = 12	GSK1292263 800 mg n = 13	Placebo n = 11
Any AE	6	2	3	3	4	6	4	5	7	8	4
Any SAE	0	0	0	0	0	0	0	0	0	0	0

Population analysed: All subject Population

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: All AEs and SAEs were collected up to follow-up visit. For Part A- up to Day 26, for Part B (washout)- up to Day 28, for Part B (run-in)- up to day up to day 28 and Part B (treatment)- up to Day 26. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
80 mg Atorvastatin + 800 mg GSK1292263 (Part A)	0 of 4 (0%)	0 of 4 (0%)	0 of 4
800 mg GSK1292263 (Part A)	0 of 2 (0%)	2 of 2 (100%)	0 of 2
Pre-treatment (Part B)	0 of 281 (0%)	14 of 281 (5%)	0 of 281
Washout (Part B)	0 of 281 (0%)	37 of 281 (13.2%)	0 of 281
Atorvastatin 10 mg (Part B Run-in)	0 of 62 (0%)	19 of 62 (30.6%)	0 of 62
Atorvastatin 80 mg (Part B Run-in)	0 of 27 (0%)	8 of 27 (29.6%)	0 of 27
Atorvastatin 10 mg + GSK1292263 100 mg (Part B Treatment)	0 of 11 (0%)	6 of 11 (54.5%)	0 of 11
Atorvastatin 10 mg + GSK1292263 300 mg (Part B Treatment)	0 of 11 (0%)	2 of 11 (18.2%)	0 of 11
Atorvastatin 10 mg + GSK1292263 800 mg (Part B Treatment)	0 of 11 (0%)	3 of 11 (27.3%)	0 of 11
Atorvastatin 10 mg + Placebo (Part B Treatment)	0 of 12 (0%)	3 of 12 (25%)	0 of 12
Atorvastatin 10 mg + Ezetimibe 10 mg (Part B Treatment)	0 of 13 (0%)	4 of 13 (30.8%)	0 of 13
Atorvastatin 80 mg + GSK1292263 800 mg (Part B Treatment)	0 of 12 (0%)	6 of 12 (50%)	0 of 12
Atorvastatin 80 mg + Placebo (Part B Treatment)	0 of 13 (0%)	4 of 13 (30.8%)	0 of 13
GSK1292263 100 mg (Part B Treatment)	0 of 11 (0%)	5 of 11 (45.5%)	0 of 11
GSK1292263 300 mg (Part B Treatment)	0 of 12 (0%)	7 of 12 (58.3%)	0 of 12
GSK1292263 800 mg (Part B Treatment)	0 of 13 (0%)	8 of 13 (61.5%)	0 of 13

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

21 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 10mg atorvastatin, 80mg atorvastatin and 100mg GSK1292263 in people with Dyslipidaemias and Dyslipidemias, run by GlaxoSmithKline at 21 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)- Part A (time frame: Up to Day 26). The study lists 41 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01218204.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2019.

Trial summary

Key requirements

Who may be able to join

Who cannot join

Trial locations and contacts

About this study

What participants receive

What is being measured

Timeline

Resources

More details

Study at a glance

Clinical summary

Study design

Who may qualify

Key inclusion criteria (13 listed)

Key exclusion criteria (43 listed)

Interventions

Primary outcome

Results and safety

Participant flow

Primary outcome: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)- Part A

Primary outcome: Number of Participants With Any AEs and SAEs- Part B (Washout)

Primary outcome: Number of Participants With Any AEs and SAEs- Part B (Run-in)

Primary outcome: Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm)

Adverse events

Research links

Related trials for Dyslipidaemias

Improved Medication and Care to Achieve Lipid Targets After Carotid Surgery

Assessment of Compliance With European and French Guidelines for the Management of Dyslipidaemias

Referral and contact

Questions about this trial

Participant flow

Primary outcome: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)- Part A

Primary outcome: Number of Participants With Any AEs and SAEs- Part B (Washout)

Primary outcome: Number of Participants With Any AEs and SAEs- Part B (Run-in)

Primary outcome: Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm)

Adverse events