SB-659032 Platelet Aggregation Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01745458
First received: December 6, 2012
Last updated: NA
Last verified: December 2012
History: No changes posted
  Purpose

This study is designed to assess whether inhibition of plasma Lp-PLA2 activity impacts platelet function as assessed by ex vivo platelet aggregation tests and in vivo plasma biomarkers.


Condition Intervention Phase
Atherosclerosis
Drug: SB-659032
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: A Double Blind Study to Evaluate Effects of Repeat Doses of SB-659032 on Platelet Aggregation in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Platelet aggregation [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
    Percent maximum platelet aggregation following ADP- and collagen-induced aggregation

  • Biomarkers of platelet aggregation [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
    Urinary 11-dehydrothromboxane B2 and blood CD62 concentrations


Secondary Outcome Measures:
  • Lp-PLA2 inhibition [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    Lp-PLA2 activity, expressed in terms of percent inhibition relative to baseline

  • Clinical safety data [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    spontaneous adverse event reporting, 12-Lead ECG, vital signs, nursing/physician observation and safety and laboratory tests

  • Mean concentrations of SB-659032 and its major metabolite, SB-664601 [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    SB-659032 and SB-664601 concentrations

  • Frequency and intensity of odor-related adverse events [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    The frequency and intensity of odor-related adverse events as reported by subjects will be summarized


Enrollment: 26
Study Start Date: July 2005
Study Completion Date: December 2005
Primary Completion Date: December 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SB-659032
250 mg non-enteric coated SB-659032
Drug: Placebo
Matched placebo
Placebo Comparator: Placebo
matched placebo QD for 14 days
Drug: SB-659032

Detailed Description:

SB-659032 is a selective and orally active inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2) that is being developed for the treatment of atherosclerosis. This study is designed to assess whether inhibition of plasma Lp-PLA2 activity impacts platelet function as assessed by ex vivo platelet aggregation tests and in vivo plasma biomarkers. Blood samples for PK analysis and measurement of Lp-PLA2 activity will also be collected. Questionnaires will be completed to evaluate the frequency of odorrelated AEs with non-enteric coated formulation of SB-659032 relative to placebo. This will be a double blind, repeat dose, randomized, placebo-controlled, two period, period balanced, crossover study. There will be a minimum of a 21 day washout period between dosing in each period.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy adult males between 18 and 55 years of age, inclusive
  • Body weight greater than 50 kg (110 pounds) and body mass index (BMI) between 19 and 32 where: BMI = weight in kg/(height in meters)2
  • A signed and dated written informed consent prior to admission to the study
  • The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.

Exclusion Criteria:

  • Any clinically relevant abnormality identified on the screening medical assessment, laboratory examination or ECG
  • Platelet count below or above the reference range
  • History of hypercoagulable state or history of thrombosis
  • History of platelet dysfunction
  • A known history of Gilbert's Syndrome
  • History of asthma, anaphylaxis or anaphalactoid reactions, severe allergic responses
  • A history of alcohol, substance or drug abuse within the last year or a positive alcohol breath test at screening or predose in each period. Abuse of alcohol is defined as an average weekly intake of greater than or equal to 21 units (male) or an average daily intake of greater than or equal to 3 units (male). 1 unit is equivalent to a 285mL glass of full strength beer or 425 mL schooner of light beer or 1 (30 mL) measure of spirits or 1 glass (100 mL) of wine
  • Positive urine drug screen at screening or predose in each period
  • History of use of tobacco or nicotine containing products within 6 months of screening or a positive urine cotinine at screening or exhaled carbon monoxide test at predose in each period
  • Positive HIV, Hepatitis B or Hepatitis C at screening
  • Use of aspirin, aspirin-containing products, non-steroidal anti-inflammatory agents or any antiplatelet medication within 14 days prior to Day -1 of the study (a list of these drugs will be reviewed with the subject at screening and provided to them to take home)
  • Use of prescription (including hormone replacement therapy) or non-prescription drugs and vitamins within 7 days or 5 half-lives (whichever is longer) prior to Day -1 of the study. An exception is acetaminophen which is allowed at doses of ≤ 2g/day
  • 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 Day -1 of the study
  • Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to dosing
  • Consumption of grapefruit or grapefruit juice within 7 days prior to Day -1 of the study
  • A history of cholecystectomy or biliary tract disease including a history of liver disease with elevated liver function tests of known or unknown etiology
  • An unwillingness to abstain from sexual intercourse with pregnant or lactating women or an unwillingness to use a condom and another form of contraception (e.g., IUD, birth control pills taken by female partner, diaphragm with spermicide) 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 or donation of blood in excess of 250 mL within 7 days prior to dosing
  • Full ADP- and/or collagen-induced aggregation (greater than and equal to 40%) at all three concentrations of one or both agonists, as assessed within 6 months prior to first dose and at Day -1 of each period
  • No ADP- or collagen-induced aggregation (less than 40%) at the highest concentration of either agonist, as assessed within 6 months prior to first dose and at Day -1 of each period
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01745458

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

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01745458     History of Changes
Other Study ID Numbers: 104623
Study First Received: December 6, 2012
Last Updated: December 6, 2012
Health Authority: Australia: Human Research Ethics Committe

Additional relevant MeSH terms:
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 28, 2014