GSK2647544 RD, DDI in Healthy Young and Elderly Volunteers

NCT ID: NCT01978327

Last Updated: 2017-06-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-22
• Study Completion Date: 2014-03-03

Brief Summary

GSK2647544 is an orally available, selective inhibitor of Lp PLA2 that is being developed for the treatment of Alzheimer's disease. The current study is a single-blind, randomised, placebo-controlled, 4-cohort study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of repeat doses of GSK2647544. Cohorts 1, 2 and 3 will evaluate escalating doses of GSK2647544 in young healthy volunteers for 7 days, 7 days, and 14 days, respectively. Cohort 4 will evaluate repeat doses of GSK2647544 in healthy elderly volunteers for 14 days. Additionally, Cohorts 1 and 3 will include an assessment of potential drug-drug interaction with simvastatin to examine CYP3A4 inhibition by GSK2647544.

Conditions

Alzheimer's Disease

Study Design

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

Study Groups

GSK2647544

The planned repeat doses of GSK2647544 are 80 mg bid, 200 mg bid, and 350 mg bid

Group Type: EXPERIMENTAL

GSK2647544

Intervention Type: DRUG

repeat dose

Placebo

Matching placebo

Group Type: PLACEBO_COMPARATOR

GSK2647544

Intervention Type: DRUG

repeat dose

simvastatin

for drug-drug interaction

Group Type: EXPERIMENTAL

drug-drug interaction

Intervention Type: DRUG

drug-drug interaction

simvastatin co-dosed with GSK2647544

for drug-drug interaction

Group Type: EXPERIMENTAL

drug-drug interaction

Intervention Type: DRUG

drug-drug interaction

Interventions

GSK2647544

repeat dose

Intervention Type: DRUG

drug-drug interaction

drug-drug interaction

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Males and females who are 18 to 64 years of age inclusive, defined as young subjects in this study, are eligible for Cohorts 1-3 only
• Males and females who are ≥65 years of age, defined as elderly subjects in this study, are eligible for Cohort 4 only
• Healthy as determined by a responsible and experienced physician
• A female subject is eligible to participate if she is of non-childbearing potential
• Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods
• Body weight > 50 kg (110 pounds) and body mass index (BMI) between 19 and 32
• 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 msec
• Capable of giving written informed consent

Exclusion Criteria

• Subjects 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
• 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 6 months of the study
• Unable to abstain from alcohol or caffeine or xanthine-containing products for 24 h prior to the start of dosing
• 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
• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening (Note: This applies to healthy young subjects screened for Cohorts 1-3 only. Healthy elderly subjects for cohort 4 who are social smokers must give up smoking for the period that they will be on the unit)
• positive pre-study drug/alcohol screen
• Unable to refrain from consumption of Seville oranges, grapefruit or grapefruit juice within 7 days prior to the first dose of study medication until the follow-up visit
• Subjects who have taken statins, medicines that are contraindications of statins, know potent inhibitiors or inducers of CYP3A4 in the 4 weeks or 5 half-lives (whichever is longer) prior to screening and are not able to discontinue use throughout participation in the clinical trial

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• 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

Harrow, Middlesex, United Kingdom

Countries

United Kingdom

Study Documents

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Other Identifiers

200592

Identifier Type: -

Identifier Source: org_study_id