GSK2647544 RD, DDI in Healthy Young and Elderly Volunteers

June 7, 2017 updated by: GlaxoSmithKline

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Middlesex
      • Harrow, Middlesex, United Kingdom, HA1 3UJ
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Matching placebo
Drug: GSK2647544
repeat dose
Experimental: GSK2647544
The planned repeat doses of GSK2647544 are 80 mg bid, 200 mg bid, and 350 mg bid
Drug: GSK2647544
repeat dose
Experimental: simvastatin
for drug-drug interaction
Drug: drug-drug interaction
drug-drug interaction
Experimental: simvastatin co-dosed with GSK2647544
for drug-drug interaction
Drug: drug-drug interaction
drug-drug interaction

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety and tolerability of GSK2647544 as assessed by number of subjects with adverse events (AE)s
Time Frame: up to 19 days in each dosing session
Safety and tolerability parameters will include recording of AEs
up to 19 days in each dosing session
Safety and tolerability of GSK2647544 as assessed by change from Baseline in laboratory values
Time Frame: up to 15 days in each dosing session
Safety and tolerability parameters will include laboratory (haematology, clinical chemistry, urinalysis) values at Screening, Day-1, Day 1 to up to Day 15 and Follow-up (7-14 days post-last dose)
up to 15 days in each dosing session
Safety and tolerability of GSK2647544 as assessed by change from Baseline in ECG readings
Time Frame: up to 19 days in each dosing session
Safety and tolerability parameter will include the electrocardiogram (ECG) readings at Screening, Day -1, Day 1 to up to Day 19, and follow-up (7-14 days post-last dose)
up to 19 days in each dosing session
Safety and tolerability of GSK2647544 as assessed by change from Baseline in Telemetry ECG parameters
Time Frame: 2 days in Cohorts 1, 2 and 4; 3 days in Cohort 4
Safety and tolerability parameter will include the Telemetry ECG readings from 30 minutes pre-dosing till 24 hours post-dosing
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
Time Frame: up to 19 days in each dosing session
Vital signs measurement include systolic and diastolic blood pressure and pulse rate at Screening, Day -1, Day 1 to up to Day 19, and Follow-up (7-14 days post-last dose)
up to 19 days in each dosing session
Safety and tolerability of GSK2647544 as assessed by Columbia Suicide Severity Rating Scale (C-SSRS)
Time Frame: 4 days in Cohorts 1 and 2; 8 days in Cohorts 3 and 4
C-SSRS will be measured at Screening, Day-1, dispersed days during dosing sessions, prior to discharge, and Follow-up (7-14 days post-last dose)
4 days in Cohorts 1 and 2; 8 days in Cohorts 3 and 4
Peak plasma concentration (Cmax) of GSK2647544
Time Frame: up to 17 days in GSK2647544 dosing sessions
To assess PK profile of GSK2647544, Cmax of GSK2647544 will be measured
up to 17 days in GSK2647544 dosing sessions
Time of peak plasma concentration (tmax) of GSK2647544
Time Frame: up to 17 days in GSK2647544 dosing sessions
To assess PK profile of GSK2647544, tmax of GSK2647544 will be measured
up to 17 days in GSK2647544 dosing sessions
Area under the time concentration curve (AUC) of GSK2647544
Time Frame: up to 17 days in GSK2647544 dosing sessions
To assess PK profile of GSK2647544, AUC of GSK2647544 will be measured
up to 17 days in GSK2647544 dosing sessions
Terminal half-life (t½ ) of GSK2647544
Time Frame: up to 17 days in GSK2647544 dosing sessions
To assess PK profile of GSK2647544, t1/2 of GSK2647544 will be measured
up to 17 days in GSK2647544 dosing sessions
Time of peak plasma concentration (tmax) of simvastatin
Time Frame: 4 days in Cohorts 1 and 3
To assess the effect of GSK2647544 on PK profile of simvastatin, tmax of simvastatin will be measured
4 days in Cohorts 1 and 3
Area under the time concentration curve (AUC) of simvastatin
Time Frame: 4 days in Cohorts 1 and 3
To assess the effect of GSK2647544 on PK profile of simvastatin, AUC of simvastatin will be measured
4 days in Cohorts 1 and 3

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Predose plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and postdose Lp-PLA2 activity
Time Frame: up to 18 days in GSK2647544 dosing sessions
Lp-PLA2 activity will be measured at Days 1, 2, 3 and 4 in GSK2647544 single dose sessions; it will be measured at Days 1, 3, 4, 5, 7, 10, 14, 15, 16, 17 and 18 in GSK2647544 repeat dose sessions
up to 18 days in GSK2647544 dosing sessions

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GlaxoSmithKline

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 22, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 3, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 3, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 31, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 31, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 7, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 8, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 7, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 200592

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

  1. Dataset Specification
    Information identifier: 200592
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  2. Clinical Study Report
    Information identifier: 200592
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  3. Informed Consent Form
    Information identifier: 200592
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  4. Individual Participant Data Set
    Information identifier: 200592
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  5. Annotated Case Report Form
    Information identifier: 200592
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  6. Study Protocol
    Information identifier: 200592
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  7. Statistical Analysis Plan
    Information identifier: 200592
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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