Dose-escalation Study of GSK2330672 in Japanese Healthy Male Volunteers

NCT ID: NCT02801981

Last Updated: 2016-11-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2016-08-31

Brief Summary

This study will be the first to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics following single dose of 10 milligrams (mg) to 180 mg of GSK2330672 in Japanese healthy subjects. This is a double-blind, randomized, placebo-controlled, dose-escalating and incomplete block crossover study to be conducted in 16 Japanese healthy subjects. Study will be conducted in four periods; subjects will receive either placebo or GSK2330672 (10 mg, 30 mg, 90 mg or 180 mg based on randomization) in each treatment period. Each period will be separated by washout period (at least 6 days from dosing). Total duration of study for each subject will be approximately 5 weeks from the first dosing to follow up visit.

Conditions

Cholestasis

Keywords

tolerability; healthy volunteers; Cholestasis; safety

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Sequence 1: GSK2230672 10mg, 30mg, 90mg, and Placebo

Subjects will receive GSK2230672 10 mg in period 1, GSK2230672 30 mg in Period 2, GSK2230672 90 mg in Period 3 and placebo in period 4.

Group Type: EXPERIMENTAL

GSK2230672

Intervention Type: DRUG

It will be supplied as white to slightly colored, round, film coated tablet for oral administration containing 10 mg or 45 mg of GSK2330672.

Placebo

Intervention Type: DRUG

It will be supplied as placebo tablets (with no GSK2230672) visually matching to GSK2230672

Sequence 2:GSK2230672 10mg, 30mg, Placebo, and GSK2230672 90mg

Subjects will receive GSK2230672 10 mg in period 1, GSK2230672 30 mg in Period 2, placebo in period 3, and GSK2230672 90 mg in period 4.

Group Type: EXPERIMENTAL

GSK2230672

Intervention Type: DRUG

It will be supplied as white to slightly colored, round, film coated tablet for oral administration containing 10 mg or 45 mg of GSK2330672.

Placebo

Intervention Type: DRUG

It will be supplied as placebo tablets (with no GSK2230672) visually matching to GSK2230672

Sequence 3:GSK2230672 10mg, Placebo, GSK2230672 90mg and 180mg

Subjects will receive GSK2230672 10 mg in period 1, placebo in Period 2, GSK2230672 90 mg in Period 3 and GSK2230672 180 mg in period 4.

Group Type: EXPERIMENTAL

GSK2230672

Intervention Type: DRUG

It will be supplied as white to slightly colored, round, film coated tablet for oral administration containing 10 mg or 45 mg of GSK2330672.

Placebo

Intervention Type: DRUG

It will be supplied as placebo tablets (with no GSK2230672) visually matching to GSK2230672

Sequence 4: Placebo, GSK2230672 30mg, 90mg and 180mg

Subjects will receive placebo in period 1, GSK2230672 30 mg in Period 2, GSK2230672 90 mg in Period 3 and GSK2230672 180 mg in period 4.

Group Type: EXPERIMENTAL

GSK2230672

Intervention Type: DRUG

It will be supplied as white to slightly colored, round, film coated tablet for oral administration containing 10 mg or 45 mg of GSK2330672.

Placebo

Intervention Type: DRUG

It will be supplied as placebo tablets (with no GSK2230672) visually matching to GSK2230672

Interventions

GSK2230672

It will be supplied as white to slightly colored, round, film coated tablet for oral administration containing 10 mg or 45 mg of GSK2330672.

Intervention Type: DRUG

Placebo

It will be supplied as placebo tablets (with no GSK2230672) visually matching to GSK2230672

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Japanese male aged between 20 and 64 years of age inclusive, at the time of signing the informed consent

Exclusion Criteria

• Regular bowel movement >=1 per two days.
• Body weight >= 50 kilogram and body mass index (BMI) is more than or equal to 18.5 kilogram / square meter (kg/m^2) and less than 25.0 kg/m^2
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.

• Alanine transaminase (ALT) and/or bilirubin >1.5x Upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome)
• QT interval corrected for heart rate according to Fridericia's formula (QTcF) > 450 millisecond (msec)
• Current or chronic history of inflammatory bowel disease, chronic diarrhea, Crohn's disease or malabsorption syndromes.
• Current or chronic history of cholelithiasis, inflammatory gall bladder disease, cholestatic liver injury, and cholecystecomy.
• Fecal occult blood test positive at screening.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (includes St. John's Wort) within 14 days or 5 half-lives, whichever is longer, prior to the first dose of study medication.
• History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 drinks. One drink is equivalent to 12 grams (g) of alcohol: 350 millilitre (mL) of beer, 150 mL of wine or 45 mL of 80 proof distilled spirits.
• History or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• 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 Medical Monitor, contraindicates their participation
• A positive pre-study syphilis, Hepatitis B surface antigen, Hepatitis C antibody, Human Immunodeficiency Virus (HIV) antigen antibody or Human T-cell Lymphotropic Virus-1 (HTLV-1) antibody result of screening
• A positive pre-study urine drug screen.
• History of donation of blood or blood products >= 400 mL within 3 months or >= 200 mL within 1 month prior to screening.
• The subject has participated in a clinical trial and has received an investigational product within four months or 5 half-lives (whichever is longer) prior to the dosing day in the current study
• Exposure to more than four new chemical entities within 12 months prior to the dosing day.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Tokyo, , Japan

Countries

Japan

Other Identifiers

205808

Identifier Type: -

Identifier Source: org_study_id