DyslipidaemiasPhase 2NCT00903617
Study to Test GSK256073 in Patients With Dyslipidemia
A Phase 2 study testing GSK256073 and Niaspan in people with Dyslipidaemias and Dyslipidemias, run by GlaxoSmithKline at 11 sites in United States.
Trial summary
This is a two part study (Part A and Part B) that will first aim to establish the PK/PD relationship between exposure and lipid effects (Part A: 75 subjects), and will then confirm the effect using the most relevant dose(s) (Part B: ~90 subjects). 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?
- GSK256073 and Niaspan
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 11 sitesUnited States
- Study dates
- 15 Jun 2009to 16 Feb 2010
- 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
- Signed written informed consent prior to beginning study-related procedures. Subjects must understand the aims, investigational procedures and possible consequences of the study and must be able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
- Male or female 18-75 years of age at screening.
- 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.
- Male subjects must agree to use one of several pre-specified contraception methods. This criterion must be followed from the time of the first dose of study medication until three days following the last dose.
- Body weight > 50 kg (110 pounds) and body mass index (BMI) between 19 and 39 (inclusive)
- LDLc concentration ≥100 mg/dL at screening and within 4 weeks of randomization (if screening occurs > 4 weeks prior to randomization)
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- Fasting triglyceride concentration ≤ 300 mg/dL at screening and within 4 weeks of randomization (if screening occurs > 4 weeks prior to randomization)
- HDLc ≤ 45 mg/dL for males or ≤ 55 mg/dL for females at screening and within 4 weeks of randomization (if screening occurs > 4 weeks prior to randomization)
- Subject currently receiving lipid-modifying medication(s) must agree to stop medication(s) for at least 6 weeks prior to randomization. After this washout period LDL, TG and HDL values must be remeasured and meet the above criteria prior to randomization in the study
- AST and ALT < 2xULN; alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Who cannot join
- Evidence of clinical instability based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk and will not interfere with the study procedures.
- 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.
- Any change in diet, exercise habits or smoking status within six weeks prior to screening.
- A medical history significant for the following:
- Clinical cardiovascular disease, including history or current evidence of coronary heart disease, heart failure, cerebrovascular disease, peripheral vascular disease, and/or a 10-year risk of CHD > 20% while on or titrated off lipid lowering medication. Subjects pending diagnostic procedures for any of those conditions at the time of screening will not be eligible for participation.
- Renal impairment (for males) as defined by a calculated GFR < 60 mL/min . Renal impairment (for females) as defined by a calculated GFR < 55 ml/min.
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- 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. glitazones, sulfonylureas, insulin, metformin, etc.).
- History of anemia or treatment of anemia within 12 months of screening or Hgb or Hct below the lower limit of reference range for age and gender at screening
- History of pancreatitis
- Any concurrent serious illness (e.g., severe COPD, HIV positive, liver cirrhosis, 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
- Active peptic ulcer disease (PUD) and/or history of PUD or other gastrointestinal bleeding within 12 months prior to screening.
- History of kidney stones
- History of gout and/or hyperuricemia or taking drugs for hyperuricemia: allopurinol and/or probenecid
- History of Gilbert's syndrome
- Current inadequately controlled hypertension (blood pressure ≥160 mmHg systolic or ≥100 mmHg diastolic at screening). If blood pressure medication is changed, blood pressure will be re-measured after 6 weeks and must again meet these criteria.
- An unwillingness of subjects currently taking aspirin to reduce the daily dose to 81 mg starting 2 weeks prior to first dose and until the follow-up visit.
- Creatinine phosphokinase (CPK) 2X ULN at screening.
- A serum uric acid exceeding by ≥ 15% the upper limit of the reference range at screening.
- PT and/or aPTT above the reference range.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- The subject has a positive pre-study drug 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.
- Use of the following blood pressure medications is prohibited at any dose: enalapril, losartan, captopril
- If subjects are titrated or switched to alternative therapy they must be on a stable dose for at least 4 weeks prior to randomization.
- Subjects will be excluded if they require treatment with systemic corticosteroids
- Subjects will be excluded if they take quinolone antibiotics, methotrexate, ibuprofen or other medication secreted by renal OAT transporters
- 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 (i.e. GSK256073 or Niaspan), or components thereof or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation
- Where participation in study would result in donation of blood in excess of 500 mL within a 56 day period.
- A positive test for HIV antibody.
- Subject is mentally or legally incapacitated.
- Unwillingness or inability to follow the procedures outlined in the protocol.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
GSK Investigational Site
Auburn, Maine, 04210
GSK Investigational Site
Brooklyn Center, Minnesota, 55430
GSK Investigational Site
Cincinnati, Ohio, 45246
GSK Investigational Site
Indianapolis, Indiana, 46260
GSK Investigational Site
Louisville, Kentucky, 40213
GSK Investigational Site
Olympia, Washington, 98502
GSK Investigational Site
Pembroke Pines, Florida, 33026
GSK Investigational Site
Richmond, Virginia, 23294
GSK Investigational Site
San Antonio, Texas, 78205
GSK Investigational Site
Seattle, Washington, 98104
GSK Investigational Site
Statesville, North Carolina, 28677
About this study
Official title: A Two Part, Multicenter Phase IIa, Placebo Controlled Study, to Examine the Safety, Tolerability, and Effects of GSK256073 on Lipids in Subjects With Dyslipidemia
This is a two part study (Part A and Part B) that will first aim to establish the PK/PD relationship between exposure and lipid effects (Part A: 75 subjects), and will then confirm the effect using the most relevant dose(s) (Part B: ~90 subjects). Doses of 5mg, 50mg and 150mg of GSK256073 will be administered in Part A, and the dose(s) for Part B will be based on the PK/PD data from Part A. Data from Part A and Part B will be combined to decrease overall subject numbers needed in part B. Part B of the study will include a niaspan arm for relative comparison of the effects of GSK256073 and niacin on lipids and flushing
- Conditions
- Dyslipidaemias, Dyslipidemias
- Being tested
- GSK256073, Placebo, Niaspan
- Keywords
- lipids, HM74A
- Medical subject headings
- Dyslipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK256073Drug
5 mg for 8 weeks
GSK256073Drug
50 mg for 8 weeks
GSK256073Drug
150 mg for 8 weeks
PlaceboDrug
placebo for 8 weeks
NiaspanDrug
1500 mg for 8 weeks
GSK256073Drug
x mg for 8 weeks based from data from Part A
GSK256073Drug
optional dose based on data from Part A
| Study group | Role | What they receive |
|---|---|---|
| Part A Treatment A | Experimental | 5 mg of GSK256073 Receives: Drug: GSK256073 |
| Part A Treatment B | Experimental | 50 mg of GSK256073 Receives: Drug: GSK256073 |
| Part A Treatment C | Experimental | 150 mg of GSK256073 Receives: Drug: GSK256073 |
| Part A Treatment D | Placebo comparator | placebo Receives: Drug: Placebo |
| Part B Treatment A | Placebo comparator | placebo Receives: Drug: Placebo |
| Part B Treatment B | Active comparator | 1500 mg Niaspan Receives: Drug: Niaspan |
| Part B Treatment C | Experimental | x mg dose of GSK256073 based on data from Part A Receives: Drug: GSK256073 |
| Part B Treatment D | Experimental | optional dose of GSK256073 based on data from Part A Receives: Drug: GSK256073 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The GSK256073 Area Under Concentration-time Curve (AUC) and High Density Lipoprotein Cholesterol (HDLc) Data to Evolve the Exposure-response Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship for Changes in HDLc Levels
The potential PK/PD relationship was to be assessed by plotting GSK256073 AUCs against HDLc. The PK/PD model that was to be used for the simulations in the study design was to be refined with the Part A observed AUC exposures and HDLc levels. However, the study was stopped for futility at the end of Part A due to lack of a compelling PK/PD relationship between GSK256073 and lipid effects that would predict success in achieving significant HDLc raising.
Measured: Week 2, 4, 6 and 8
Secondary outcomes (22)
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is 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, medically significant or it is associated with liver injury and impaired liver function.
Measured: Up to follow up (14 days from last dose)
Number of Participants With Electrocardiography (ECG) Findings
Single 12-lead ECGs was obtained at each time point during the study using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QTc intervals. Participants with normal, abnormal- clinically significant (CS) and abnormal- not clinically significant (NCS) ECG values were reported.
Measured: Up to Week 8
Change From Baseline in Vital Signs-Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP and DBP was assessed at Baseline (Week 0), Week 2, 4, 6 and 8. Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the post-Baseline value from the Baseline value.
Measured: Baseline (Week 0) up to Week 8
Change From Baseline in Vital Signs-Heart Rate
Heart rate was assessed at Baseline (Week 0), Week 2, 4, 6 and 8. Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the post-Baseline value from the Baseline value.
Measured: Baseline (Week 0) up to Week 8
Number of Participants With Abnormal Hematology Values
Blood samples for assessment of hematology parameters of platelet count, red blood cell count, white blood cell count, hemoglobin, haptoglobin, reticulocyte count, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, neutrophils, lymphocytes, monocytes, eosinophils and basophils was collected at Baseline and at Weeks 2, 4, 6 and 8.
Measured: Baseline (Week 0) up to Week 8
Number of Participants With Abnormal Clinical Chemistry Values
Blood samples for assessment of clinical chemistry parameters of blood urea nitrogen, creatinine, glucose (fasting), sodium, creatine phosphokinase, potassium, chloride, total carbon dioxide, calcium, total lactose dehydrogenase (LDH), aspartate aminotransferase (AST), alanine amino transferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, phosphate, total and direct bilirubin, uric acid, albumin and total protein was collected at Baseline and at Weeks 2, 4, 6 and 8.
Measured: Up to Week 8
Number of Participants With Abnormal Urinalysis Results
Urinalysis assessment was done for urine occult blood, urine glucose, urine ketones and urine protein over eight weeks treatment period.
Measured: Up to Week 8
Average Global Flushing Score
Flushing assessment was captured by participants in individual diaries provided to each study participant. Participants were instructed to return their diaries after each study visit (Week 2, Week 4, Week 6 and Week 8) where they were given a new diary for the time between visits. Flushing symptom questionnaire (FSQ) was used to measure participant reported feelings of severity associated with different types of flushing symptoms. The FSQ comprised of 11 items. The response scale combined verbal descriptors as well as a 0-10 numerical rating scale. Items 1, 2, 4 and 10 had verbal descriptors. The items 3, 5, 6, 7, 8, 9 and 11 were rated on a 0 to 10 scale (none=0, mild=1-3, moderate=4-6, severe=7-9 and extreme=10). The total score for these items ranged from 0 (not at all) to 70 (extreme). Higher score indicated more severe flushing symptoms and 0 indicated no flushing symptoms.
Measured: Up to Week 8
Number of Participants With Self Reported Assessment of Flushing
Flushing assessment was captured by participants in individual diaries provided to each study participant. Participants were instructed to return their diaries after each study visit (Week 2, Week 4, Week 6 and Week 8) where they were given a new diary for the time between visits. Participants were asked to perform an assessment of their perceived flushing intensity after their completion of VAS assessment once daily after their first flushing episode (if more than one happens to occur). The scale was from 0 to 3, where 0 represents no flushing, 1 represents mild flushing, 2 represents moderate flushing, and 3 represents severe flushing.
Measured: Up to Week 8
Average Number of Flushing Episodes
Flushing assessment was captured by participants in individual diaries provided to each study participant. Participants were instructed to return their diaries after each study visit (Week 2, Week 4, Week 6 and Week 8) where they were given a new diary for the time between visits. Participants with average number of flushing episodes was reported as "did not have flushing episode", "1 flushing episode", "2 flushing episode" and "3 or more flushing episode".
Measured: Up to Week 8
Average Time to Onset of Flushing
Flushing assessment was captured by participants in individual diaries provided to each study participant. Participants were instructed to return their diaries after each study visit (Week 2, Week 4, Week 6 and Week 8) where they were given a new diary for the time between visits. The time to the onset of the first flushing (if more than one happens to occur on each day) was analyzed.
Measured: Up to Week 8
Participant's Average Duration of Flushing
Flushing assessment was captured by participants in individual diaries provided to each study participant. Participants were instructed to return their diaries after each study visit (Week 2, Week 4, Week 6 and Week 8) where they were given a new diary for the time between visits. Participant's average duration of flushing was analyzed.
Measured: Up to Week 8
Number of Participants Who Withdrew Due to Flushing
Flushing assessment was captured by participants in individual diaries provided to each study participant. Participants were instructed to return their diaries after each study visit (Week 2, Week 4, Week 6 and Week 8) where they were given a new diary for the time between visits.
Measured: Up to follow up (14 days from last dose)
Mean Episode of Flushing as Measured by Visual Analogue Scale (VAS)
Flushing assessment was captured by participants in individual diaries provided to each study participant. Participants were instructed to return their diaries after each study visit (Week 2, Week 4, Week 6 and Week 8) where they were given a new diary for the time between visits. Participants self-assessed intensity of flushing using a 100 mm VAS once daily at the first flushing episode. The left hand side of the scale (0) represented 'No Flushing Sensation' and the right hand side of the scale (100) represented 'Unbearable Flushing Sensation'. The intensity of flushing of each episode was measured in centimeters (to the nearest 1/100) from the 0 point of the scale. Data is reported for average VAS scores over 8 weeks of treatment.
Measured: Up to Week 8
Percent Change From Baseline in Fasting Plasma HDLc and Apolipoprotein A-I (ApoA1) Concentrations Over Eight Weeks of Administration With GSK256073 or Placebo
Blood samples for analysis of fasting levels of HDLc and ApoA1 was collected at Baseline (Week 0) and Week 2, 4, 6 and 8. Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the post-Baseline value from the Baseline value. Percent change from Baseline was calculated by multiplying change from baseline value with 100.
Measured: Baseline (Week 0) up to Week 8
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo
Blood samples for analysis of fasting levels of TC, TG, glucose, LDLc, ApoAII and ApoB was collected at Baseline (Week 0) and Week 2, 4, 6 and 8. Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the post-Baseline value from the Baseline value. Percent change from Baseline was calculated by multiplying change from baseline value with 100.
Measured: Baseline (Week 0) up to Week 8
Percent Change From Baseline in Insulin Over Eight Weeks of Administration With GSK256073 or Placebo
Blood samples for analysis of insulin was collected at Baseline (Week 0) and Week 2, 4, 6 and 8. Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the post-Baseline value from the Baseline value. Percent change from Baseline was calculated by multiplying change from Baseline value with 100.
Measured: Baseline (Week 0) up to Week 8
Percent Change From Baseline in Lipoprotein (a) (Lp[a]) Over Eight Weeks of Administration With GSK256073 or Placebo
Blood samples for analysis of Lp[a] was collected at Baseline (Week 0) and Week 2, 4, 6 and 8. Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the post-Baseline value from the Baseline value. Percent change from Baseline was calculated by multiplying change from Baseline value with 100.
Measured: Baseline (Week 0) up to Week 8
Percent Change From Baseline in Non-esterified Fatty Acids (NEFA) Over Eight Weeks of Administration With GSK256073 or Placebo
Blood samples for analysis of NEFA was collected at Baseline (Week 0) and Week 2, 4, 6 and 8. Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the post-Baseline value from the Baseline value. Percent change from Baseline was calculated by multiplying change from Baseline value with 100.
Measured: Baseline (Week 0) up to Week 8
Plasma PK- Maximum Observed Concentration (Cmax)
All participants treated with GSK256073 or placebo participated in PK sampling. Blood samples for PK analysis of GSK256073 to determine Cmax was collected at Week 2, 4, 6 and 8. For samples obtained during time windows, every attempt was made to collect three samples during each time window: pre-dose to 2 hours after dosing, 2 hours to 4.5 hours after dose, and 6 hours to 12 hours after dose. During each window, 3 samples spaced at least 30 minutes apart were collected (i.e., avoid collection from all participants at the same time within a window or only at the extremes of a time window). The first occurrence of the Cmax was determined directly from the raw concentration-time data.
Measured: 0-2 hours after dosing (pre-dose plus 3 samples spaced at least 30 minutes apart), 2 to 4.5 hours after dose (3 samples spaced at least 30 minutes apart) and 6-12 hours post dose (3 samples spaced at least 30 minutes apart) on Week 2, 4, 6 and 8
Plasma PK- Time of Occurrence of Cmax (Tmax)
All participants treated with GSK256073 or placebo participated in PK sampling. Blood samples for PK analysis of GSK256073 to determine Tmax was collected at Week 2, 4, 6 and 8. For samples obtained during time windows, every attempt was made to collect three samples during each time window: pre-dose to 2 hours after dosing, 2 hours to 4.5 hours after dose, and 6 hours to 12 hours after dose. During each window, 3 samples spaced at least 30 minutes apart were collected (i.e., avoid collection from all participants at the same time within a window or only at the extremes of a time window). The time at which Cmax was observed was determined directly from the raw concentration-time data.
Measured: 0-2 hours after dosing (pre-dose plus 3 samples spaced at least 30 minutes apart), 2 to 4.5 hours after dose (3 samples spaced at least 30 minutes apart) and 6-12 hours post dose (3 samples spaced at least 30 minutes apart) on Week 2, 4, 6 and 8
Plasma PK- AUC(0-t)
All participants treated with GSK256073 or placebo participated in PK sampling. Blood samples for PK analysis of GSK256073 to determine AUC(0-t) was collected at Week 2, 4, 6 and 8. For samples obtained during time windows, every attempt was made to collect three samples during each time window: pre-dose to 2 hours after dosing, 2 hours to 4.5 hours after dose, and 6 hours to 12 hours after dose. During each window, 3 samples spaced at least 30 minutes apart were collected (i.e., avoid collection from all participants at the same time within a window or only at the extremes of a time window). The AUC 0-t was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
Measured: 0-2 hours after dosing (pre-dose plus 3 samples spaced at least 30 minutes apart), 2 to 4.5 hours after dose (3 samples spaced at least 30 minutes apart) and 6-12 hours post dose (3 samples spaced at least 30 minutes apart) on Week 2, 4, 6 and 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2009 (estimated)
- Study start15 Jun 2009
- Primary completion16 Feb 2010
- Study completion16 Feb 2010
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.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00903617
- Sponsor's protocol ID
- 112795
- Status last verified
- Nov 2019
- First submitted
- 14 May 2009
- Last updated
- 5 Dec 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.
Publications
Olson EJ, Mahar KM, Haws TF, Fossler MJ, Gao F, de Gouville AC, Sprecher DL, Lepore JJ. A Randomized, Placebo-Controlled Trial to Assess the Effects of 8 Weeks of Administration of GSK256073, a Selective GPR109A Agonist, on High-Density Lipoprotein Cholesterol in Subjects With Dyslipidemia. Clin Pharmacol Drug Dev. 2019 Oct;8(7):871-883. doi: 10.1002/cpdd.704. Epub 2019 Jul 3.
PubMed 31268250
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two Part, Multicenter Phase IIa, Placebo Controlled Study, to Examine the Safety, Tolerability, and Effects of GSK256073 on Lipids in Subjects With Dyslipidemia
- ClinicalTrials.gov ID
- NCT00903617
- Acronym / sponsor ID
- 112795
- Conditions
- Dyslipidaemias, Dyslipidemias
- Keywords
- lipids, HM74A
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 15 Jun 2009 (actual)
- Primary completion
- 16 Feb 2010 (actual)
- Study completion
- 16 Feb 2010 (actual)
- First posted
- 18 May 2009 (estimated)
- Results
- Posted 21 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a two part study (Part A and Part B) that will first aim to establish the PK/PD relationship between exposure and lipid effects (Part A: 75 subjects), and will then confirm the effect using the most relevant dose(s) (Part B: ~90 subjects). Doses of 5mg, 50mg and 150mg of GSK256073 will be administered in Part A, and the dose(s) for Part B will be based on the PK/PD data from Part A. Data from Part A and Part B will be combined to decrease overall subject numbers needed in part B. Part B of the study will include a niaspan arm for relative comparison of the effects of GSK256073 and niacin on lipids and flushing
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Part A Treatment A | Experimental | Drug: GSK2560735 mg of GSK256073 |
| Part A Treatment B | Experimental | Drug: GSK25607350 mg of GSK256073 |
| Part A Treatment C | Experimental | Drug: GSK256073150 mg of GSK256073 |
| Part A Treatment D | Placebo comparator | Drug: Placeboplacebo |
| Part B Treatment A | Placebo comparator | Drug: Placeboplacebo |
| Part B Treatment B | Active comparator | Drug: Niaspan1500 mg Niaspan |
| Part B Treatment C | Experimental | Drug: GSK256073x mg dose of GSK256073 based on data from Part A |
| Part B Treatment D | Experimental | Drug: GSK256073optional dose of GSK256073 based on data from Part A |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Signed written informed consent prior to beginning study-related procedures. Subjects must understand the aims, investigational procedures and possible consequences of the study and must be able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
- Male or female 18-75 years of age at screening.
- 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.
- Male subjects must agree to use one of several pre-specified contraception methods. This criterion must be followed from the time of the first dose of study medication until three days following the last dose.
- Body weight > 50 kg (110 pounds) and body mass index (BMI) between 19 and 39 (inclusive)
Key exclusion criteria (34 listed)
- Evidence of clinical instability based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk and will not interfere with the study procedures.
- 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.
- Any change in diet, exercise habits or smoking status within six weeks prior to screening.
- A medical history significant for the following:
- Clinical cardiovascular disease, including history or current evidence of coronary heart disease, heart failure, cerebrovascular disease, peripheral vascular disease, and/or a 10-year risk of CHD > 20% while on or titrated off lipid lowering medication. Subjects pending diagnostic procedures for any of those conditions at the time of screening will not be eligible for participation.
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 |
|---|---|---|
| GSK2560735 mg for 8 weeks | Drug | Part A Treatment A |
| GSK25607350 mg for 8 weeks | Drug | Part A Treatment B |
| GSK256073150 mg for 8 weeks | Drug | Part A Treatment C |
| Placeboplacebo for 8 weeks | Drug | Part A Treatment D, Part B Treatment A |
| Niaspan1500 mg for 8 weeks | Drug | Part B Treatment B |
| GSK256073x mg for 8 weeks based from data from Part A | Drug | Part B Treatment C |
| GSK256073optional dose based on data from Part A | Drug | Part B Treatment D |
Primary outcome
The GSK256073 Area Under Concentration-time Curve (AUC) and High Density Lipoprotein Cholesterol (HDLc) Data to Evolve the Exposure-response Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship for Changes in HDLc Levels
Time frame: Week 2, 4, 6 and 8
The potential PK/PD relationship was to be assessed by plotting GSK256073 AUCs against HDLc. The PK/PD model that was to be used for the simulations in the study design was to be refined with the Part A observed AUC exposures and HDLc levels. However, the study was stopped for futility at the end of Part A due to lack of a compelling PK/PD relationship between GSK256073 and lipid effects that would predict success in achieving significant HDLc raising.
22 secondary outcomes
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to follow up (14 days from last dose)
Number of Participants With Electrocardiography (ECG) Findings
Time frame: Up to Week 8
Change From Baseline in Vital Signs-Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time frame: Baseline (Week 0) up to Week 8
Change From Baseline in Vital Signs-Heart Rate
Time frame: Baseline (Week 0) up to Week 8
Number of Participants With Abnormal Hematology Values
Time frame: Baseline (Week 0) up to Week 8
Number of Participants With Abnormal Clinical Chemistry Values
Time frame: Up to Week 8
Number of Participants With Abnormal Urinalysis Results
Time frame: Up to Week 8
Average Global Flushing Score
Time frame: Up to Week 8
Number of Participants With Self Reported Assessment of Flushing
Time frame: Up to Week 8
Average Number of Flushing Episodes
Time frame: Up to Week 8
Average Time to Onset of Flushing
Time frame: Up to Week 8
Participant's Average Duration of Flushing
Time frame: Up to Week 8
Number of Participants Who Withdrew Due to Flushing
Time frame: Up to follow up (14 days from last dose)
Mean Episode of Flushing as Measured by Visual Analogue Scale (VAS)
Time frame: Up to Week 8
Percent Change From Baseline in Fasting Plasma HDLc and Apolipoprotein A-I (ApoA1) Concentrations Over Eight Weeks of Administration With GSK256073 or Placebo
Time frame: Baseline (Week 0) up to Week 8
Percent Change From Baseline in Fasting Levels of Total Cholesterol (TC), Triglyceride (TG), Glucose, Low Density Lipoprotein Cholesterol (LDLc), Apolipoprotein A2 (ApoAII), Apolipoprotein B (ApoB) Over 8 Weeks of Administration With GSK256073 or Placebo
Time frame: Baseline (Week 0) up to Week 8
Percent Change From Baseline in Insulin Over Eight Weeks of Administration With GSK256073 or Placebo
Time frame: Baseline (Week 0) up to Week 8
Percent Change From Baseline in Lipoprotein (a) (Lp[a]) Over Eight Weeks of Administration With GSK256073 or Placebo
Time frame: Baseline (Week 0) up to Week 8
Percent Change From Baseline in Non-esterified Fatty Acids (NEFA) Over Eight Weeks of Administration With GSK256073 or Placebo
Time frame: Baseline (Week 0) up to Week 8
Plasma PK- Maximum Observed Concentration (Cmax)
Time frame: 0-2 hours after dosing (pre-dose plus 3 samples spaced at least 30 minutes apart), 2 to 4.5 hours after dose (3 samples spaced at least 30 minutes apart) and 6-12 hours post dose (3 samples spaced at least 30 minutes apart) on Week 2, 4, 6 and 8
Plasma PK- Time of Occurrence of Cmax (Tmax)
Time frame: 0-2 hours after dosing (pre-dose plus 3 samples spaced at least 30 minutes apart), 2 to 4.5 hours after dose (3 samples spaced at least 30 minutes apart) and 6-12 hours post dose (3 samples spaced at least 30 minutes apart) on Week 2, 4, 6 and 8
Plasma PK- AUC(0-t)
Time frame: 0-2 hours after dosing (pre-dose plus 3 samples spaced at least 30 minutes apart), 2 to 4.5 hours after dose (3 samples spaced at least 30 minutes apart) and 6-12 hours post dose (3 samples spaced at least 30 minutes apart) on Week 2, 4, 6 and 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31268250Olson EJ, Mahar KM, Haws TF, Fossler MJ, Gao F, de Gouville AC, Sprecher DL, Lepore JJ. A Randomized, Placebo-Controlled Trial to Assess the Effects of 8 Weeks of Administration of GSK256073, a Selective GPR109A Agonist, on High-Density Lipoprotein Cholesterol in Subjects With Dyslipidemia. Clin Pharmacol Drug Dev. 2019 Oct;8(7):871-883. doi: 10.1002/cpdd.704. Epub 2019 Jul 3.
- 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
11 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 GSK256073 and Niaspan in people with Dyslipidaemias and Dyslipidemias, run by GlaxoSmithKline at 11 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 10 inclusion and 34 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 5 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 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. Some participants in this study may receive a placebo. 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 21 Sep 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?
The GSK256073 Area Under Concentration-time Curve (AUC) and High Density Lipoprotein Cholesterol (HDLc) Data to Evolve the Exposure-response Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship for Changes in HDLc Levels (time frame: Week 2, 4, 6 and 8). 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 NCT00903617, which also lists 1 linked publication.
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 5 Dec 2019.