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AnaemiaPhase 1NCT02243306

Study to Assess the Pharmacokinetics of GSK1278863 in Subjects With End Stage Renal Disease Undergoing Peritoneal Dialysis

A Phase 1 study testing GSK1278863 in people with Anaemia, run by GlaxoSmithKline at 2 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

GSK1278863 is an orally-active, novel small molecule agent which inhibits hypoxia-inducible factor (HIF) prolyl -4- hydroxylases (PHDs) and is in development for the treatment of anaemia associated with chronic kidney disease (CKD). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Anaemia
What is being tested?
GSK1278863
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
2 sitesUnited States
Study dates
24 Oct 2014to 10 May 2017
Phase
Phase 1
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • SAFETY:
  • Satisfactory medical evaluation based upon medical history, medication history, physical examination, and clinical laboratory data obtained at the Screening visit. The determination of clinical significance will be made by the Investigator and the GlaxoSmithKline (GSK) Medical Monitor and will require that the finding is unlikely to introduce additional risk factors or interfere with the study procedures, or the integrity of the study.
  • Corrected QT interval (QTc) <470 milliseconds (msec) OR QTc <480 msec in subjects with Bundle Branch Block. These should be based on average of triplicate values obtained over a brief recording period at Screening and on Day -1 and the single reading on Day 17. The same QT correction formula should be used to determine inclusion and discontinuation for any individual subject throughout the study.
  • Vitamin B12 and folate above the lower limit of normal at Screening.
  • Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and bilirubin <=1.5 x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • EFFICACY:
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  • A subject is eligible to enroll and participate in this study if he/she has ESRD and is on peritoneal dialysis for at least 2 months with an average urine output of <750 mL/daily with a combined weekly (urine and peritoneal dialysis output) Kt/V urea >1.7 measured at any time within last 3 months.
  • No history of peritoneal dialysis-associated peritonitis, peritoneal catheter tunnel (exit site) infection or leakage for at least 3 months before study.
  • Meets the following erythropoiesis stimulating agent (ESA) criteria: Is ESA naive (i.e., no ESA use within the previous 12 weeks of screening) OR agrees to discontinue ESA (if currently using ESA) for at least 7 days prior to first dose of GSK1278863 until completion of Follow-up visit (If the subject has a scheduled ESA interval which is <=7 days, ESA treatment must be discontinued for at least 7 days prior to first dose of GSK1278863. If the subject has a scheduled ESA interval which is >7 days, ESA treatment must be discontinued for at least the scheduled interval length [e.g., if ESA interval is 14 days, then ESA must be discontinued for >=14 days] prior to the first dose of GSK1278863)
  • Has a haemoglobin value: For ESA naïve subjects: <10.0 g/dL (UK site(s) only: <=11.0 g/dL); For subjects receiving ongoing ESA treatment: <=11.0 g/dL at Screening (UK site(s) only: <=12.0 g/dL at Screening).
  • OTHER:
  • Subjects who are >=18 years of age at the time of Screening.
  • A female subject is eligible to participate if she is of: (a) Childbearing potential, and agrees to use one of the contraception methods described in the protocol. This criterion must be followed from the time of Screening until completion of the Follow-up Visit; (b) 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) 23.0-116.3 international units (IU)/litre (L) and estradiol <=10 picograms (pg)/mL (or <=37 picomoles [pmol]/L) is confirmatory). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods described in the protocol if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2 months must 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 without use of a contraceptive method.
  • Body weight >45 kilograms (kg) and <140 kg at Screening.
  • The subject is mentally and legally able to comply with the requirements and restrictions of the protocol and has provided signed informed consent prior to participation in any protocol-specific procedures, including Screening procedures.

Who cannot join

  • SAFETY
  • A positive test for Human Immunodeficiency Virus (HIV) antibody.
  • Uncontrolled hypertension (diastolic blood pressure [BP] >100 millimetres of mercury [mmHg] or systolic BP >170 mmHg) at Screening.
  • History of drug abuse or dependence within 6 months of the study.
  • History of sensitivity to GSK1278863, or its components thereof or a history of drug or other allergy that, in the opinion of the Investigator or GSK Medical Monitor, contraindicates their participation.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinical research unit uses heparin to maintain intravenous cannula patency).
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  • History of thrombosis defined as deep vein thrombosis, stroke, pulmonary embolism or other thrombosis related condition within 3 months prior to Screening.
  • History of myocardial infarction or acute coronary syndrome within 3 months prior to Screening.
  • History of stroke or transient ischaemic attack within 3 months prior to Screening.
  • Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, and/or hepatic function that could interfere with the absorption, metabolism, and/or excretion of GSK1278863. Examples of conditions that could interfere with normal gastrointestinal anatomy or motility include gastrointestinal bypass surgery, partial or total gastrectomy, small bowel resection, vagotomy, malabsorption, Crohn's disease, ulcerative colitis, or celiac sprue. Examples of conditions that could interfere with hepatic function include Gilbert's syndrome.
  • Evidence of active peptic, duodenal or esophageal ulcer disease at Screening OR history of clinically significant gastro-intestinal (GI) bleeding within 3 months prior to Screening.
  • Subjects with chronic inflammatory disease that could impact erythropoiesis (e.g. scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease).
  • Subjects with a history of symptomatic right heart failure.
  • Subjects with Class III or Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
  • Active malignancy or diagnosis of malignancy within 5 years prior to Screening (excluding successfully treated basal or squamous cell carcinoma).
  • History of proliferative vascular eye disease (e.g., choroidal or retinal disease, such as neovascular age-related macular degeneration, proliferative diabetic retinopathy or macular edema) based upon having had an ophthalmologic exam within 12 months prior to the end of the Screening period (The screening period is from the screening visit until Day -1).
  • Pregnant females as determined by positive serum human chorionic gonadotropin (hCG) test at Screening or Day -1.
  • Lactating females.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period prior to first dose.
  • Consumption of red wine, grapefruit (juice), blood orange (juice), star fruit, onions, kale, broccoli, green beans, or apples from 7 days prior to the first dose of investigational product until the Follow-up visit, unless in the opinion of the Investigator and GSK Medical Monitor this will not interfere with the study procedures and compromise subject safety.
  • Use or planned use of any prescription or non-prescription drugs that are prohibited 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 GSK1278863 until completion of the follow-up visit, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  • The following medications are specifically prohibited for the duration of the study (from Screening to the follow-up visit at the end of the study): Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) with the exception of low dose (<=325 mg/day) aspirin/acetylsalicylic acid. Occasional NSAID use is permitted; Immunosuppressant drugs and drugs used to treat malignancies (including corticosteroids at doses >10 mg prednisolone per day or equivalent) within 2 weeks of first dose of GSK1278863. Note: Failed transplant subjects back on peritoneal dialysis are eligible for participating in this study but should not be on immunosuppressive medications within 3 months prior to Screening.
  • The subject has participated in a clinical trial and has received an experimental investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • EFFICACY:
  • The values of ferritin and transferrin within 3 months prior to Screening are: (a) transferrin saturation <20%; (b) serum ferritin <100 micrograms (mcg)/L
  • OTHER:
  • A positive pre-dosing drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines. A positive pre-dosing screen for medications that are prescribed to a renal subject for pre-existing condition(s), may be allowed if in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  • History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (approximately240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • History of regular use within 6 months of the study of tobacco- or nicotine-containing products in excess of 20 cigarettes per day or equivalent.
  • Unwillingness or inability to follow the procedures, or lifestyle and/or dietary restrictions outlined in the informed consent and as directed by site staff.
  • 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

2 sites in 1 country.

United States2 sites

  • GSK Investigational Site

    Lakewood, Colorado, 80228

  • GSK Investigational Site

    Minneapolis, Minnesota, 55404

Other trials in United States

About this study

Official title: A Repeat-Dose, Open-Label, Parallel-Group Study to Assess the Pharmacokinetics of GSK1278863 and Metabolites in Subjects With End Stage Renal Disease Undergoing Peritoneal Dialysis

GSK1278863 is an orally-active, novel small molecule agent which inhibits hypoxia-inducible factor (HIF) prolyl -4- hydroxylases (PHDs) and is in development for the treatment of anaemia associated with chronic kidney disease (CKD). As the kidney represents a major site of elimination for many drugs and their metabolites, and GSK1278863 will be administered to subjects with various stages of renal disease, it is important to characterize the pharmacokinetics in this target patient population. The purpose of this study is to characterize the pharmacokinetics of GSK1278863 and its metabolites in subjects with end stage renal disease (ESRD) undergoing peritoneal dialysis. This will be a repeat-dose, open-label, parallel-group study. Approximately 30 subjects with ESRD will be enrolled in two cohorts (15 subjects in each cohort) to ensure that 6 subjects on continuous ambulatory peritoneal dialysis (CAPD) (cohort 1) and 6 subjects on automated peritoneal dialysis APD (cohort 2) complete dosing and critical assessments. GSK1278863 will be administered once daily for 14 days. Primary pharmacokinetic assessments will be made on Days 1 and 14.

Conditions
Anaemia
Being tested
GSK1278863
Keywords
pharmacokinetics, Chronic kidney disease, peritoneal dialysis, hemoglobin, Anemia, GSK1278863, Prolyl hydroxylase inhibitor, erythropoiesis stimulating agents
Medical subject headings
Anemia, Renal Insufficiency, Chronic

What participants receive

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

  • GSK1278863Drug

    Round, biconvex, white film coated tablet containing 5 mg GSK1278863.

Study groups in NCT02243306
Study groupRoleWhat they receive
Cohort 1ExperimentalSubjects on continuous ambulatory peritoneal dialysis (CAPD) will receive 5 mg of GSK1278863 orally, once daily for 14 days.
Receives: Drug: GSK1278863
Cohort 2ExperimentalSubjects on automated peritoneal dialysis (APD) will receive 5 mg of GSK1278863 orally, once daily for 14 days
Receives: Drug: GSK1278863

What is being measured

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

  1. Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites

    Serial blood samples were collected from participants at indicated time points for Pharmacokinetic (PK) analysis of GSK1278863 and its metabolites (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531403 and GSK2531401). Geometric mean and geometric coefficient of variation has been presented for all metabolites. NA indicates data is not available. Geometric coefficient of variation could not be calculated for CAPD cohort due to small number of participants. PK Population comprised of participants in the 'All Subjects' Population for whom a PK sample was obtained and analyzed.

    Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours post-dose on Day 1; Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose on Day 14

  2. AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-inf]) of GSK1278863 and Its Metabolites

    Serial blood samples were collected from participants at indicated time points for PK analysis of GSK1278863 and its metabolites (GSK2487818 and GSK2531398). Geometric mean and geometric coefficient of variation has been presented for all metabolites. NA indicates data is not available. Geometric coefficient of variation could not be calculated for CAPD cohort due to small number of participants.

    Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours post-dose on Day 1

  3. Maximum Observed Concentration (Cmax) of GSK1278863 and Its Metabolites

    Serial blood samples were collected from participants at indicated time points for PK analysis of GSK1278863 and its metabolites (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531403 and GSK2531401). Geometric mean and geometric coefficient of variation has been presented for all metabolites. NA indicates data is not available. Geometric coefficient of variation could not be calculated for CAPD cohort due to small number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

    Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours post-dose on Day 1; Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose on Day 14

Secondary outcomes (25)

  1. Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)

    An AE is 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. 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, is a congenital anomaly/birth defect, other situations, and is associated with liver injury and impaired liver function. Analysis was performed on All Subjects Population which comprised of all enrolled participants who received at least one dose of study treatment.

    Measured: Up to Day 24

  2. Change From Baseline in Glucose, Calcium, Chloride, Carbon-dioxide (CO2), Potassium, Sodium and Urea Levels

    Blood samples were collected from participants to evaluate clinical chemistry parameters including glucose, calcium, chloride, CO2, potassium, sodium and urea. Change from Baseline in clinical chemistry parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed.

    Measured: Baseline and Day 17

  3. Change From Baseline in Albumin and Protein Levels

    Blood samples were collected from participants to evaluate clinical chemistry parameters including albumin and protein. Change from Baseline in clinical chemistry parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed.

    Measured: Baseline and Day 17

  4. Change From Baseline in Direct Bilirubin, Bilirubin, Creatinine and Urate Levels

    Blood samples were collected from participants to evaluate clinical chemistry parameters including direct bilirubin, bilirubin, creatinine and urate. Change from Baseline in clinical chemistry parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed.

    Measured: Baseline and Day 17

  5. Change From Baseline in Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Gamma Glutamyl Aminotransferase (GGT) Levels

    Blood samples were collected from participants to evaluate clinical chemistry parameters including ALP, AST and GGT. Change from Baseline in clinical chemistry parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed.

    Measured: Baseline and Day 17

  6. Change From Baseline in Alanine Aminotransferase (ALT) and Creatinine Kinase Levels

    Blood samples were collected from participants to evaluate clinical chemistry parameters including ALT and creatinine kinase. Change from Baseline in clinical chemistry parameters at Day 3, Day 7, Day 11, Day 14 and Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

    Measured: Baseline and Day 3, 7, 11, 14, 17

  7. Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Levels

    Blood samples were collected from participants to evaluate clinical hematology parameters including basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelets and leukocytes. Change from Baseline in clinical hematology parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. NA indicates data is not available. Mean and standard deviation are presented. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed.

    Measured: Baseline and Day 17

  8. Change From Baseline in Erythrocyte and Reticulocyte Levels

    Blood samples were collected from participants to evaluate clinical hematology parameters including erythrocyte and reticulocyte. Change from Baseline in clinical hematology parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. NA indicates data is not available. Mean and standard deviation are presented. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed.

    Measured: Baseline and Day 17

  9. Change From Baseline in Hematocrit Levels

    Blood samples were collected from participants to evaluate clinical hematology parameters including hematocrit. Change from Baseline in clinical hematology parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed.

    Measured: Baseline and Day 17

  10. Change From Baseline in Hemoglobin Levels

    Blood samples were collected from participants to evaluate clinical hematology parameters including hemoglobin. Change from Baseline in clinical hematology parameters at Day 3, Day 7, Day 11 and Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

    Measured: Baseline and Day 3, 7, 11, 17

  11. Change From Baseline in Mean Corpuscular Hemoglobin Concentration (MCHC)

    Blood samples were collected from participants to evaluate clinical hematology parameters including MCHC. Change from Baseline in clinical hematology parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed.

    Measured: Baseline and Day 17

  12. Change From Baseline in Mean Corpuscular Volume (MCV)

    Blood samples were collected from participants to evaluate clinical hematology parameters including MCV. Change from Baseline in clinical hematology parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed.

    Measured: Baseline and Day 17

  13. Change From Baseline in Mean Corpuscular Hemoglobin (MCH) Levels

    Blood samples were collected from participants to evaluate clinical hematology parameters including MCH. Change from Baseline in clinical hematology parameters at Day 17 are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only participants with data available at the specified time point were analyzed.

    Measured: Baseline and Day 17

  14. Number of Participants With Abnormal Electrocardiogram (ECG) Findings

    Single measurements of 12-lead ECG were obtained in supine position after at least 10 minutes of rest using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and corrected QT (QTc) interval. Participants with abnormal ECG findings at worst-case observation Carried Forward for triplicate measurements (WOCF) post-Baseline visit are presented. Only participants with data available at WOCF visit were analyzed.

    Measured: Day 17

  15. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

    Vital sign measurements including SBP and DBP were taken in a supine position after at least 5 minutes of rest. Change from Baseline in SBP and DBP at Day 17 and Day 24 (follow-up) are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

    Measured: Baseline, Day 17 and Day 24

  16. Change From Baseline in Pulse Rate

    Vital sign measurements including pulse rate were taken in a supine position after at least 5 minutes of rest. Change from Baseline in pulse rate at Day 17 and Day 24 (follow-up) are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

    Measured: Baseline, Day 17 and Day 24

  17. Change From Baseline in Body Temperature

    Vital sign measurements including body temperature were taken in a supine position after at least 5 minutes of rest. Change from Baseline in body temperature at Day 17 and Day 24 (follow-up) are presented. Day-1 was considered as Baseline value. Change from Baseline was calculated as post-randomization values minus Baseline value. Mean and standard deviation are presented. NA indicates data is not available. Standard deviation could not be calculated for CAPD cohort due to small number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

    Measured: Baseline, Day 17 and Day 24

  18. Number of Participants With Abnormal Physical Examination Findings

    A complete physical examination was planned to include assessments of the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes and extremities. This analysis was planned but not performed. Any significant finding was captured as an AE.

    Measured: Up to Day 17

  19. Peritoneal Dialysis Clearance of GSK1278863 and Metabolites

    Peritoneal dialysate samples for PK analysis of GSK1278863 and metabolites (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531403 and GSK2531401) were collected. Peritoneal dialysis clearance of GSK1278863 and metabolites was calculated from Day 14 dialysate excretion data as total amount of analyte excreted over 24 hours divided by plasma AUC (0-tau). Geometric mean and geometric coefficient of variation are presented. NA indicates data is not available. Geometric coefficient of variation could not be calculated due to small number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

    Measured: Day 14

  20. Terminal Phase Half-life (t 1/2) of GSK1278863 and Metabolites

    Serial blood samples were collected from participants at indicated time points for PK analysis of GSK1278863 and its metabolites (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531403, GSK2531401). Geometric mean and geometric coefficient of variation have been presented for all metabolites. Geometric coefficient of variation could not be calculated for CAPD cohort due to small number of participants, which is indicated by NA. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

    Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours post-dose on Day 1; Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose on Day 14

  21. Time of Occurrence of Cmax (Tmax) of GSK1278863 and Metabolites

    Serial blood samples were collected from participants at indicated time points for PK analysis of GSK1278863 and its metabolites (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531403 and GSK2531401). Median and full range have been presented for all metabolites. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

    Measured: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours post-dose on Day 1; Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose on Day 14

  22. Accumulation Ratio of GSK1278863 and Metabolites

    The observed accumulation ratio was determined to estimate the extent of accumulation for GSK1278863 and metabolites (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531403 and GSK2531401) after repeat dosing. Accumulation ratio was calculated by using AUC (0-tau) values at Day 1 and Day 14. Analysis was performed using mixed effect model fitted with day (single and repeat dose) as fixed effect and participant as random effect. Mean ratio and 90% confidence intervals have been presented.

    Measured: Day 1 and Day 14

  23. Time Invariance Ratio of GSK1278863 and Metabolites

    Time invariance ratio for GSK1278863 and metabolites (GSK2391220, GSK2487818, GSK2506102, GSK2531398, GSK2531403 and GSK2531401) was calculated by analyzing AUC (0-inf) at Day 1 and AUC (0-tau) at Day 14. Analysis was performed using mixed effect model fitted with day (single and repeat dose) as fixed effect and participant as random effect. Mean ratio and 90% confidence intervals have been presented. NA indicates data is not available. Data could not be calculated due to insufficient data.

    Measured: Day 1 and Day 14

  24. Plasma Concentration of Erythropoietin

    Serial blood samples were collected from participants at indicated time points to analyze plasma concentration of erythropoietin after repeat-dose administration of GSK1278863. Geometric mean and geometric coefficient of variation have been presented. NA indicates data is not available. Geometric coefficient of variation could not be calculated for CAPD cohort due to small number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

    Measured: Pre-dose and 4, 8 ,12, 24 hours post-dose on Day 1 and Day 14; Pre-dose on Day 3, 7, 11

  25. Plasma Concentration of Hepcidin

    Serial blood samples were collected from participants at indicated time points to analyze plasma concentration of hepcidin after repeat-dose administration of GSK1278863. Geometric mean and geometric coefficient of variation have been presented. NA indicates data is not available. Geometric coefficient of variation could not be calculated for CAPD cohort due to small number of participants. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

    Measured: Pre-dose and 4, 8 ,12, 24 hours post-dose on Day 1 and Day 14; Pre-dose on Day 3, 7, 11

Timeline

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

  1. First posted17 Sep 2014 (estimated)
  2. Study start24 Oct 2014
  3. Primary completion10 May 2017
  4. Study completion10 May 2017

Resources

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 1
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02243306
Sponsor's protocol ID
200942
Other IDs
2014-001197-34, 2014
Status last verified
Mar 2019
First submitted
29 May 2014
Last updated
9 Apr 2019
Data monitoring committee
No

Publications

  • Caltabiano S, Cizman B, Burns O, Mahar KM, Johnson BM, Ramanjineyulu B, Serbest G, Cobitz AR. Effect of renal function and dialysis modality on daprodustat and predominant metabolite exposure. Clin Kidney J. 2019 Feb 18;12(5):693-701. doi: 10.1093/ckj/sfz013. eCollection 2019 Oct.

    PubMed 31583094

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK1278863 in people with Anaemia, run by GlaxoSmithKline at 2 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 15 inclusion and 31 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 9 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 11 Mar 2019). 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?

Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC[0-tau]) of GSK1278863 and Its Metabolites (time frame: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours post-dose on Day 1; Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose on Day 14). The study lists 3 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 NCT02243306, 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 9 Apr 2019.

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