Dose-escalation Study of GSK2330672 in Japanese Healthy Male Volunteers

NCT02801981 | Completed Phase 1

• 1 other identifier: 205808
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (9)

• Number of Subjects with Adverse events (AE)

  Maximum of 5 weeks

• Safety as assessed by blood pressure

  Systolic and diastolic blood pressure will be measured on Day -1, post dose 2 hours (hrs), 12.5 hrs, 24.5 hrs and at 48 hrs in each period and at follow-up.

  Maximum of 5 weeks

• Safety as assessed by heart rate

  Heart rate will be measured on Day -1, post dose 2 hrs, 12.5 hrs, 24.5 hrs and at 48 hrs in each period and at follow-up.

  Maximum of 5 weeks

• Safety as assessed by body temperature

  Body temperature will be measured on Day -1, post dose 2 hrs, 12.5 hrs, 24.5 hrs and at 48 hrs in each period and at follow-up.

  Maximum of 5 weeks

• Safety as assessed by clinical chemistry parameters

  Blood sample will be collected on Day -1, at 48 hrs in each period and at follow-up

  Maximum of 5 weeks

• Safety as assessed by haematology

  Blood sample will be collected on Day -1, at 48 hrs in each period and at follow-up

  Maximum of 5 weeks

• Safety as assessed by urinalysis

  Sample will be collected on Day -1, at 48 hrs in each period and at follow-up

  Maximum of 5 weeks

• Safety as assessed by fecal occult blood

  Fecal occult blood testing will be conducted on Screening (2 samples during Screening period) and each dosing period (anytime from dosing to next dose).

  Maximum of 5 weeks

• Safety as assessed by Electrocardiogram (ECG)

  Electrocardiogram will be measured on Day -1, post dose 2 hrs, 12.5 hrs, 24.5 hrs and at 48 hrs in each period and at follow-up.

  Maximum of 5 weeks

Secondary Outcomes (1)

• Plasma concentration of GSK2330672

  Blood samples will be collected predose and post dose at 0.5 hrs, 2 hr, 3.5 hr, 5 hr on Day 1 of each period

Study Arms (4)

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

EXPERIMENTAL

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.

Drug: GSK2230672; Drug: Placebo

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

EXPERIMENTAL

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.

Drug: GSK2230672; Drug: Placebo

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

EXPERIMENTAL

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.

Drug: GSK2230672; Drug: Placebo

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

EXPERIMENTAL

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.

Drug: GSK2230672; Drug: Placebo

Interventions

GSK2230672 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.

Sequence 1: GSK2230672 10mg, 30mg, 90mg, and Placebo; Sequence 2:GSK2230672 10mg, 30mg, Placebo, and GSK2230672 90mg; Sequence 3:GSK2230672 10mg, Placebo, GSK2230672 90mg and 180mg; Sequence 4: Placebo, GSK2230672 30mg, 90mg and 180mg

Placebo DRUG

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

Sequence 1: GSK2230672 10mg, 30mg, 90mg, and Placebo; Sequence 2:GSK2230672 10mg, 30mg, Placebo, and GSK2230672 90mg; Sequence 3:GSK2230672 10mg, Placebo, GSK2230672 90mg and 180mg; Sequence 4: Placebo, GSK2230672 30mg, 90mg and 180mg

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Tokyo, 192-0071, Japan

Location

MeSH Terms

Conditions

Cholestasis

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2016
• First Posted: June 16, 2016
• Study Start: June 1, 2016
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: November 9, 2016

Record last verified: 2016-11

Locations

JP (1)