Last updated: 11/07/2018 11:47:50
GSK2647544 RD, DDI in healthy young and elderly volunteers
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Other
Other
Trial overview
Official title: Single-blind, randomised, placebo-controlled study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of repeat doses of GSK2647544 and its potential pharmacokinetic interaction with simvastatin in healthy volunteers
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Single (Participant)
Allocation:
Randomized
Primary outcomes:
Safety and tolerability of GSK2647544 as assessed by number of subjects with adverse events (AE)s
Timeframe: up to 19 days in each dosing session
Safety and tolerability of GSK2647544 as assessed by change from Baseline in laboratory values
Timeframe: up to 15 days in each dosing session
Safety and tolerability of GSK2647544 as assessed by change from Baseline in ECG readings
Timeframe: up to 19 days in each dosing session
Safety and tolerability of GSK2647544 as assessed by change from Baseline in Telemetry ECG parameters
Timeframe: 2 days in Cohorts 1, 2 and 4; 3 days in Cohort 4
Safety and tolerability of GSK2647544 as assessed by change from Baseline in vital signs
Timeframe: up to 19 days in each dosing session
Safety and tolerability of GSK2647544 as assessed by Columbia Suicide Severity Rating Scale (C-SSRS)
Timeframe: 4 days in Cohorts 1 and 2; 8 days in Cohorts 3 and 4
Peak plasma concentration (Cmax) of GSK2647544
Timeframe: up to 17 days in GSK2647544 dosing sessions
Time of peak plasma concentration (tmax) of GSK2647544
Timeframe: up to 17 days in GSK2647544 dosing sessions
Area under the time concentration curve (AUC) of GSK2647544
Timeframe: up to 17 days in GSK2647544 dosing sessions
Terminal half-life (t½ ) of GSK2647544
Timeframe: up to 17 days in GSK2647544 dosing sessions
Time of peak plasma concentration (tmax) of simvastatin
Timeframe: 4 days in Cohorts 1 and 3
Area under the time concentration curve (AUC) of simvastatin
Timeframe: 4 days in Cohorts 1 and 3
Secondary outcomes:
Predose plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and postdose Lp-PLA2 activity
Timeframe: up to 18 days in GSK2647544 dosing sessions
Interventions:
Enrollment:
12
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Wu K, Xu J, Fong R, Yao X, Xu Y, Guiney W, Gray F, Lockhart A. Evaluation of the safety, pharmacokinetics, pharmacodynamics and drug-drug interaction potential of a selective Lp-PLA2 inhibitor (GSK2647544) in healthy volunteers. Int J Clin Pharmacol Ther. 2016;54(12):935-949.
Medical condition
Alzheimer's Disease
Product
GSK2647544, simvastatin
Collaborators
Not applicable
Study date(s)
November 2013 to March 2014
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
Yes
- 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
- 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
Inclusion and exclusion 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
Trial location(s)
Location
GSK Investigational Site
Harrow, Middlesex, United Kingdom, HA1 3UJ
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Other
Actual primary completion date
Not applicable
Actual study completion date
2014-03-03
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study 200592 can be found on the GSK Clinical Study Register.
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