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

NCT02348372 | Completed Phase 1

• 1 other identifier: 115385
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Anaemia

Outcome Measures

Primary Outcomes (5)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  up to 96 hr

• AUC(0-t), AUC(0-∞), Cmax, tmax and t½ of GSK1278863A

  up to 96 hr

• Changes from Baseline of Clinical laboratory tests

  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

  0,2448 and 96 hr

• Changes from Baseline of Vital signs

  systolic and diastolic blood pressure and pulse rate

  0, 1,2,3,4,8 and 24hr

• Change from Baseline of 12-lead ECG

  0,4 and 8 hr

Secondary Outcomes (1)

• Hemoglobin endpoints: Hemoglobin actual values, change from baseline, rate of rise/decline, maximum change from baseline, and maximum % change from baseline

  up to 96 hr

Study Arms (5)

GSK1278863A Placebo

PLACEBO COMPARATOR

5, 25 and 100 mg matched

Drug: GSK1278863A Placebo; Drug: GSK1278863A

GSK1278863A 10mg

EXPERIMENTAL

A round, biconvex, white film coated tablet

Drug: GSK1278863A Placebo; Drug: GSK1278863A

GSK1278863A 25mg

EXPERIMENTAL

A round, biconvex, white film coated tablet

Drug: GSK1278863A

GSK1278863A 50mg

EXPERIMENTAL

A round, biconvex, white film coated tablet

Drug: GSK1278863A

GSK1278863A 100mg

EXPERIMENTAL

A round, biconvex, white film coated tablet

Drug: GSK1278863A

Interventions

GSK1278863A Placebo DRUG

Matching size, shape and color

GSK1278863A 10mg; GSK1278863A Placebo

GSK1278863A DRUG

A round, biconvex, white film coated tablet

GSK1278863A 100mg; GSK1278863A 10mg; GSK1278863A 25mg; GSK1278863A 50mg; GSK1278863A Placebo

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Randwick, Sydney, New South Wales, 2031, Australia

Location

Related Links

• Results for study 115385 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Anemia

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2012
• First Posted: January 28, 2015
• Study Start: March 31, 2011
• Primary Completion: June 3, 2011
• Study Completion: June 3, 2011
• Last Updated: June 22, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)