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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01702467
First Posted: October 8, 2012
Last Update Posted: October 18, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
The current study will examine the safety, tolerability, plasma pharmacokinetics (PK), and plasma pharmacodynamics (PD) of single-doses of GSK2647544.The study will be conducted as a randomized, single-blind, placebo controlled, 4-way crossover single oral ascending dose design in 2 independent cohorts, eight healthy male subjects in each of the cohorts. Each potential subject will undergo Screening visit, Treatment Phase and Follow-up visit.

Condition Intervention Phase
Alzheimer's Disease Drug: GSK2647544 Drug: Placebo Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: A Single-Blind, Randomized, Placebo-Controlled Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single, Oral Escalating Doses of GSK2647544 in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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 ]
    Safety and tolerability parameters will include recording of AEs

  • 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 ]
    Safety and tolerability parameters will include laboratory (haematology, clinical chemistry, urinalysis) values at Screening, Day -1, Day 3 and Follow-up (7-14 days post-last dose)

  • 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 ]
    Safety and tolerability parameter will include the electrocardiogram (ECG) readings at Screening, Day -1, Day 1, Day 2, Day 3 and Follow-up (7-14 days post-last dose)

  • 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 ]
    Safety and tolerability parameter will include the Telemetry ECG readings from 30 minutes pre-dosing till 48 hours post-dosing

  • 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 ]
    Vital signs measurement include systolic and diastolic blood pressure and pulse rate at Screening, Day -1, Day 1, Day 2, Day 3, Day 4 and Follow-up (7-14 days post-last dose)

  • 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 ]
    C-SSRS will be measured at Screening, Day -1, Day 1 (conducted prior to discharge) and Follow-up (7-14 days post-last dose)


Secondary Outcome Measures:
  • Peak plasma concentration (Cmax) of GSK2647544 [ Time Frame: 4 Days in each of the 4 dosing session ]
    To assess PK profile of GSK2647544, Cmax of GSK2647544 will be measured

  • Time of peak plasma concentration (tmax) of GSK2647544 [ Time Frame: 4 Days in each of the 4 dosing session ]
    To assess PK profile of GSK2647544 tmax of GSK2647544 will be measured

  • Area under the time concentration curve (AUC) of GSK2647544 [ Time Frame: 4 Days in each of the 4 dosing session ]
    To assess PK profile of GSK2647544 AUC of GSK2647544 will be measured

  • Terminal half-life (t½ ) of GSK2647544 [ Time Frame: 4 Days in each of the 4 dosing session ]
    To assess PK profile of GSK2647544 t½ of GSK2647544 will be measured

  • Apparent oral clearance (CL/F) of GSK2647544 [ Time Frame: 4 Days in each of the 4 dosing session ]
    To assess PK profile of GSK2647544 CL/F of GSK2647544 will be measured

  • Predose plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and postdose Lp-PLA2 activity [ Time Frame: 5 Days in each of the 4 dosing session ]
    It will be measured at Day 1, Day 2, Day 3, Day 4 and Day 5


Enrollment: 27
Actual Study Start Date: October 19, 2012
Study Completion Date: May 15, 2013
Primary Completion Date: May 15, 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK2647544
The starting dose of GSK2647544 is 0.5 mg. The escalating doses to be administered will be determined based on study results from previous dose (s).
Drug: GSK2647544
Capsules containing 0.5mg to 50mg of GSK2647544.
Placebo Comparator: Placebo
Matching placebo
Drug: Placebo
Matching placebo capsules.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01702467


Locations
Australia, New South Wales
GSK Investigational Site
Randwick, New South Wales, Australia, 2031
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 116698
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 116698
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 116698
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 116698
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 116698
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 116698
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 116698
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01702467     History of Changes
Other Study ID Numbers: 116698
First Submitted: October 4, 2012
First Posted: October 8, 2012
Last Update Posted: October 18, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
URL: http://

Keywords provided by GlaxoSmithKline:
Lp-PLA2
Alzheimer's disease

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders