Clinical trial NCT02801981: Dose-escalation Study of GSK2330672 in Japanese Healthy Male Volunteers
Official title: A Double-blind, Randomized, Placebo Controlled, Dose Escalating Crossover Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Parameters of Single Doses of GSK2330672 in Japanese Healthy Male Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cholestasis
Keywords: tolerability
healthy volunteers
Cholestasis
safety
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2016-06-16
Enrollment: 16
Sex: MALE
Minimum age (years): 20
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* Japanese male aged between 20 and 64 years of age inclusive, at the time of signing the informed consent
* Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and 12-lead ECG. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator (in consultation with the Medical Monitor if required) agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Number of Subjects with Adverse events (AE)
timeFrame: Maximum of 5 weeks
measure: Safety as assessed by blood pressure
timeFrame: Maximum of 5 weeks
measure: Safety as assessed by heart rate
timeFrame: Maximum of 5 weeks
measure: Safety as assessed by body temperature
timeFrame: Maximum of 5 weeks
measure: Safety as assessed by clinical chemistry parameters
timeFrame: Maximum of 5 weeks
measure: Safety as assessed by haematology
timeFrame: Maximum of 5 weeks
measure: Safety as assessed by urinalysis
timeFrame: Maximum of 5 weeks
measure: Safety as assessed by fecal occult blood
timeFrame: Maximum of 5 weeks
measure: Safety as assessed by Electrocardiogram (ECG)
timeFrame: Maximum of 5 weeks
Secondary outcomes:
measure: Plasma concentration of GSK2330672
timeFrame: 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
Other outcomes:
Locations:
city: Tokyo
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: