CompletedPhase 1

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single, Oral Escalating Doses of GSK2647544 in Healthy Volunteers

A Single-Blind, Randomized, Placebo-Controlled Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single, Oral Escalating Doses of GSK2647544 in Healthy Volunteers

Lead sponsor

GlaxoSmithKline

Asset

GSK2647544

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Age 18-55•Male

Primary endpoint

•Safety and tolerability of GSK2647544

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID116698

NCT IDNCT01702467

Timeline

Milestones

Study first posted2012-10-08estimated

Study start2012-10-19actual

Primary completion2013-05-15actual

Study completion2013-05-15actual

Last update posted2017-10-18actual

Assets

Drug assets

GSK2647544

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age18 Years

Maximum age55 Years

SexMale

Healthy volunteersAccepted

Inclusion criteria

•Healthy males who are 18 to 55 years of age, inclusive

•Healthy as determined by a responsible and experienced physician

•aspartate aminotransferase (AST), Alanine transaminase (ALT), alkaline phosphatase and bilirubin <= 1.5xUpper Limit of Normal (ULN)

•Average of triplicate QTcB values and average of triplicate QTcF values must both < 450 millisecond (msec)

•Body weight > 50 kg (110 pounds) and body mass index (BMI) between 19 and 30

•Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods

•Capable of giving written informed consent

Exclusion criteria

•Those with Lp-PLA2 activity <=20 nanomole/minute/milliliter (mL)(for subjects with 2 known birth parents of at least 50% Japanese, Chinese, or Korean ancestry)

•History of asthma, anaphylaxis or anaphalactoid reactions, severe allergic responses

•History of hypercoagulable state or history of thrombosis

•A history of biliary tract disease including a history of liver disease with elevated liver function tests of known or unknown etiology

•Positive Human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C at screening

•History of regular use of tobacco- or nicotine-containing products within three months of the study and/or has a positive breath CO at screening

•History of alcohol consumption exceeding, on average, 21 drinks/week for men (1 drink = 100 mL of wine or 240 mL of beer or 30 mL of hard liquor in Australia) within 6 months of the first dose of study medication

•Positive urine drug or positive breath alcohol test at screening or at admission to Clinical Research Unit

•Unable to refrain from use of prescription or non-prescription drugs and vitamins within 7 days or 5 half-lives (whichever is longer) prior to administration of study

•Unable to refrain from use of dietary/herbal supplements including (but not limited to) St. John's wort, kava, ephedra (ma huang), gingko biloba, DHEA, yohimbe, saw palmetto, ginseng and red yeast rice within 14 days prior to treatment with study medication

•Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to dosing

•Unable to refrain from consumption of grapefruit or grapefruit juice within 7 days prior to the first dose of study medication

•For male subjects, an unwillingness to abstain from sexual intercourse with pregnant or lactating women or an unwillingness to use a condom plus partner use of a highly effective contraceptive if engaging in sexual intercourse with a woman who could become pregnant until discharge from the study

•Donation of blood in excess of 500 mL within 56 days prior to dosing

•History of sensitivity to heparin or heparin-induced thrombocytopenia

•Subjects, who in the investigator's judgement, pose a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behaviour and/or any suicidal ideation of type 4 or 5 on the C-SSRS in the last 6 months

Endpoints (12)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Safety / tolerability / PK

Other (unclassified)

Safety / tolerability / PK

10 endpoints

Primary/protocol endpoint

Safety and tolerability of GSK2647544 as assessed by number of subjects with adverse events (AE)s

Time frame:5 days in each of the 4 dosing session

event count, event

Primary/protocol endpoint

Safety and tolerability of GSK2647544 as assessed by change from Baseline in laboratory values

Time frame:5 days in each of the 4 dosing session

change from baseline, event

Primary/protocol endpoint

Safety and tolerability of GSK2647544 as assessed by change from Baseline in ECG readings

Time frame:5 days in each of the 4 dosing session

change from baseline, event

Primary/protocol endpoint

Safety and tolerability of GSK2647544 as assessed by change from Baseline in Telemetry ECG parameters

Time frame:3 Days in each of the 4 dosing session

change from baseline, event

Primary/protocol endpoint

Safety and tolerability of GSK2647544 as assessed by change from Baseline in vital signs

Time frame:5 days in each of the 4 dosing session

change from baseline, event

Primary/protocol endpoint

Safety and tolerability of GSK2647544 as assessed by using the Columbia Suicide Severity Rating Scale (C-SSRS)

Time frame:5 days in each of the 4 dosing session

descriptive

Secondary/protocol endpoint

Peak plasma concentration (Cmax) of GSK2647544