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Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of GSK1278863A in Healthy Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02348372
Recruitment Status : Completed
First Posted : January 28, 2015
Last Update Posted : June 22, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE April 5, 2012
First Posted Date  ICMJE January 28, 2015
Last Update Posted Date June 22, 2017
Actual Study Start Date  ICMJE March 31, 2011
Actual Primary Completion Date June 3, 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 22, 2015)
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: up to 96 hr ]
  • AUC(0-t), AUC(0-∞), Cmax, tmax and t½ of GSK1278863A [ Time Frame: up to 96 hr ]
  • Changes from Baseline of Clinical laboratory tests [ Time Frame: 0,2448 and 96 hr ]
    Platelet Count , RBC Indices, WBC Differential, RBC Count, WBC Count, Lymphocytes, Reticulocyte Count, Hemoglobin, Hematocritm, BUN, Ptassium, AST, Total and direct bilirubin, Creatinine, Chloride, ALT, Uric Acid, Glucose, Total CO2, GGT, Albumin, Sodium, Calcium, Alkaline phosphatase, Total Protein, CPK, Iron Ferritin, TIBC
  • Changes from Baseline of Vital signs [ Time Frame: 0, 1,2,3,4,8 and 24hr ]
    systolic and diastolic blood pressure and pulse rate
  • Change from Baseline of 12-lead ECG [ Time Frame: 0,4 and 8 hr ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2015)
Hemoglobin endpoints: Hemoglobin actual values, change from baseline, rate of rise/decline, maximum change from baseline, and maximum % change from baseline [ Time Frame: up to 96 hr ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of GSK1278863A in Healthy Subjects
Official Title  ICMJE A Phase I, Randomized, Single-Blind, Placebo-Controlled, Dose-Escalation (Part 1), Fixed Sequence and Open-Label (Part 2), Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of GSK1278863A in Healthy Subjects
Brief Summary GSK1278863A is a novel small molecule agent, which stimulates erythropoiesis through inhibition of hypoxia-inducible factor (HIF)-prolyl hydroxylases (EGLNs). This compound is being developed for the treatment of anemia. This study, PHI115385, will be the first administration of GSK1278863A to Japanese subjects to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses in healthy Japanese adult subjects. Healthy Caucasian adult subjects will be included in order to compare pharmacokinetics of GSK1278863A and its metabolite(s), and pharmacodynamics of GSK1278863A.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Other
Condition  ICMJE Anaemia
Intervention  ICMJE
  • Drug: GSK1278863A Placebo
    Matching size, shape and color
  • Drug: GSK1278863A
    A round, biconvex, white film coated tablet
Study Arms  ICMJE
  • Placebo Comparator: GSK1278863A Placebo
    5, 25 and 100 mg matched
    Interventions:
    • Drug: GSK1278863A Placebo
    • Drug: GSK1278863A
  • Experimental: GSK1278863A 10mg
    A round, biconvex, white film coated tablet
    Interventions:
    • Drug: GSK1278863A Placebo
    • Drug: GSK1278863A
  • Experimental: GSK1278863A 25mg
    A round, biconvex, white film coated tablet
    Intervention: Drug: GSK1278863A
  • Experimental: GSK1278863A 50mg
    A round, biconvex, white film coated tablet
    Intervention: Drug: GSK1278863A
  • Experimental: GSK1278863A 100mg
    A round, biconvex, white film coated tablet
    Intervention: Drug: GSK1278863A
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 22, 2015)
34
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 3, 2011
Actual Primary Completion Date June 3, 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • AST, ALT, alkaline phosphatase and bilirubin >1.5xULN.
  • Healthy Male or female between 20 and 65 years of age inclusive, at the time of signing the informed consent.
  • Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods.
  • Body weight > 50 kg and BMI within the range 18.5 - 29.0 kg/m2 (inclusive).
  • Capable of giving written informed consent.
  • QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
  • Japanese defined being born in Japan, having four ethnic Japanese grandparents, holding a Japanese passport or identity papers and being able to speak Japanese. Japanese subjects should be also have lived outside Japan for less than 10 years.
  • Caucasian, defined as an individual having four grandparents who are all descendents of the original peoples of Europe.

Exclusion Criteria:

  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
  • A positive pre-study drug screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines
  • A hemoglobin value at Screening is of: Healthy male subjects or post-menopausal females: > 16.5 g/dL, Healthy female (non-childbearing potential) subjects: > 15.5 g/dL
  • The values of hematological parameters at screening are: MCV: outside the reference range and deemed clinically significant by the investigator and GSK Medical Monitor.
  • The values of the following tests at Screening, for healthy subjects are: TIBC: outside the reference range of the population being studied, Serum iron: outside the reference range of the population being studied, Serum ferritin: outside the reference range of the population being studied
  • A value at screening is greater than the upper limit of reference range for the following clinical laboratory parameters: AST, ALT, direct bilirubin.
  • Clinically significant abnormal CPK determined by the Investigator and GSK Medical Monitor.
  • Calculated creatinine clearance: < 80 mL/min
  • A positive test for HIV antibody
  • History of drug abuse or dependence within 6 months of the study.
  • History of regular alcohol consumption within 6 months of the study
  • History or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
  • 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. By exception, subject may take acetaminophen (<2 grams/day) up to 48 hours prior to the first dose of study drug.
  • History of sensitivity to any of the study medications, or 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).
  • 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 the study drugs. Examples of conditions that could interfere with normal gastrointestinal anatomy or motility include cholecystectomy, 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 Gilberts syndrome.
  • History of peptic ulcer disease or chronic rectal bleeding.
  • History of malignancy. Non-melanoma skin cancer that has been definitely removed is allowed.
  • Subjects with a baseline medical history of proliferative diabetic retinopathy, preproliferative diabetic retinopathy, or wet age-related macular degeneration (AMD).
  • Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
  • 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.
  • Unwillingness or inability to follow the procedures, or lifestyle and/or dietary restrictions outlined in the protocol.
  • Consumption of >3 servings per day 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, unless in the opinion of the Investigator and GSK Medical Monitor this will not interfere with the study procedures and compromise subject safety.
  • The subject has participated in a clinical trial and has received an 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).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • Subject is mentally or legally incapacitated.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02348372
Other Study ID Numbers  ICMJE 115385
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP