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Alzheimer's DiseasePhase 1NCT01978327

GSK2647544 RD, DDI in Healthy Young and Elderly Volunteers

A Phase 1 study testing GSK2647544 and drug-drug interaction in people with Alzheimer's Disease, run by GlaxoSmithKline at 1 site in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Alzheimer's Disease
What is being tested?
GSK2647544 and drug-drug interaction
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
12 participants
Where
1 siteUnited Kingdom
Study dates
22 Nov 2013to 3 Mar 2014
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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 locations and contacts

1 site in 1 country.

United Kingdom1 site

  • GSK Investigational Site

    Harrow, Middlesex, HA1 3UJ

Other trials in United Kingdom

About this study

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

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.

Being tested
GSK2647544, drug-drug interaction
Keywords
Alzheimer's disease, GSK2647544, drug-drug interaction, healthy subjects, Lp-PLA2, simvastatin
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK2647544Drug

    repeat dose

  • drug-drug interactionDrug

    drug-drug interaction

Study groups in NCT01978327
Study groupRoleWhat they receive
GSK2647544ExperimentalThe planned repeat doses of GSK2647544 are 80 mg bid, 200 mg bid, and 350 mg bid
Receives: Drug: GSK2647544
PlaceboPlacebo comparatorMatching placebo
Receives: Drug: GSK2647544
simvastatinExperimentalfor drug-drug interaction
Receives: Drug: drug-drug interaction
simvastatin co-dosed with GSK2647544Experimentalfor drug-drug interaction
Receives: Drug: drug-drug interaction

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Safety and tolerability parameters will include recording of AEs

    Measured: up to 19 days in each dosing session

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

    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)

    Measured: up to 15 days in each dosing session

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

    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)

    Measured: up to 19 days in each dosing session

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

    Safety and tolerability parameter will include the Telemetry ECG readings from 30 minutes pre-dosing till 24 hours post-dosing

    Measured: 2 days in Cohorts 1, 2 and 4; 3 days in Cohort 4

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

    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)

    Measured: up to 19 days in each dosing session

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

    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)

    Measured: 4 days in Cohorts 1 and 2; 8 days in Cohorts 3 and 4

  7. Peak plasma concentration (Cmax) of GSK2647544

    To assess PK profile of GSK2647544, Cmax of GSK2647544 will be measured

    Measured: up to 17 days in GSK2647544 dosing sessions

  8. Time of peak plasma concentration (tmax) of GSK2647544

    To assess PK profile of GSK2647544, tmax of GSK2647544 will be measured

    Measured: up to 17 days in GSK2647544 dosing sessions

  9. Area under the time concentration curve (AUC) of GSK2647544

    To assess PK profile of GSK2647544, AUC of GSK2647544 will be measured

    Measured: up to 17 days in GSK2647544 dosing sessions

  10. Terminal half-life (t½ ) of GSK2647544

    To assess PK profile of GSK2647544, t1/2 of GSK2647544 will be measured

    Measured: up to 17 days in GSK2647544 dosing sessions

  11. Time of peak plasma concentration (tmax) of simvastatin

    To assess the effect of GSK2647544 on PK profile of simvastatin, tmax of simvastatin will be measured

    Measured: 4 days in Cohorts 1 and 3

  12. Area under the time concentration curve (AUC) of simvastatin

    To assess the effect of GSK2647544 on PK profile of simvastatin, AUC of simvastatin will be measured

    Measured: 4 days in Cohorts 1 and 3

Secondary outcomes (1)

  1. Predose plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and postdose Lp-PLA2 activity

    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

    Measured: up to 18 days in GSK2647544 dosing sessions

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Nov 2013 (estimated)
  2. Study start22 Nov 2013
  3. Primary completion3 Mar 2014
  4. Study completion3 Mar 2014

Why it stopped: Given the strength of CYP3A4 inhibition observed in Cohort 1, there is no rationale to investigate higher doses of GSK2647544 in the following two cohorts

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Single blind
Who is masked
Participant
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01978327
Sponsor's protocol ID
200592
Status last verified
Jun 2017
First submitted
31 Oct 2013
Last updated
8 Jun 2017
Results posted
No
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK2647544 and drug-drug interaction in people with Alzheimer's Disease, run by GlaxoSmithKline at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Given the strength of CYP3A4 inhibition observed in Cohort 1, there is no rationale to investigate higher doses of GSK2647544 in the following two cohorts). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01978327.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2017.

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