A Healthy Volunteer Pharmacokinetic Study of Single and Repeat Doses of SB-480848

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00743860
First received: August 28, 2008
Last updated: November 15, 2016
Last verified: November 2016
  Purpose
This study is designed to assess the pharmacokinetics of darapladib and its metabolites following single and 28 days of repeat dosing of darapladib.

Condition Intervention Phase
Atherosclerosis
Drug: darapladib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study to Evaluate the Pharmacokinetics of the Enteric-Coated Micronized Free Base Formulation of Darapladib [SB-480848] and Its Metabolites in Healthy Volunteers.

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • The primary PK endpoints will include AUC and Cmax of darapladib and its metabolites (M10, M3 and M4) following single and repeat oral doses. Metabolite to parent AUC and Cmax ratio for each metabolite will be calculated as data permit. [ Time Frame: following single and 28 day repeat dose ]
  • Clinical safety data (spontaneous AE reporting, vital signs, nursing/physician observation, and clinical laboratory tests) will be the primary safety endpoint. [ Time Frame: throughout study ]

Secondary Outcome Measures:
  • Secondary PK endpoints will include Tmax and T½ of darapladib and its metabolites (M10, M3 and M4) as data permit. [ Time Frame: following single and 28 day repeat dose ]
  • Plasma Lp-PLA2 activity, expressed in terms of percent inhibition relative to baseline, as data permit. [ Time Frame: following single and repeat dose ]

Enrollment: 20
Study Start Date: September 2008
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single dose
single oral dose
Drug: darapladib
experimental drug
Experimental: Repeat Dose
28 day repeat dose
Drug: darapladib
experimental drug

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and ECG.
  • Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
  • A female subject is eligible to participate if she is of:
  • Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea
  • Child-bearing potential and agrees to use one of the contraception methods per protocol for an appropriate period of time prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until the follow-up visit.
  • Body weight >50 kg and BMI within the range 19 - 30 kg/m2 (inclusive).
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.

Exclusion Criteria:

  • A positive pre-study drug/alcohol screen.
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
  • A positive test for HIV antibody.
  • History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 drinks for males or >7 drinks for females.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication
  • Consumption of grapefruit or grapefruit juice within 7 days prior to first dose of study medication.
  • History of drug abuse.
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
  • History of anaphylaxis, anaphylactoid (resembling anaphylaxis) reactions or severe allergic responses.
  • History of cholecystectomy or biliary tract disease, or a history of liver disease with elevated liver function tests of known or unknown etiology.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia (if heparin is to be used for flushing a cannula).
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • Use of oral, injected and implanted hormonal methods of contraception for female subjects.
  • Pregnant females as determined by positive serum hCG test at screening or prior to dosing.
  • Lactating females.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • Subject is mentally or legally incapacitated.
  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: NCT00743860

Locations
United States, Washington
GSK Investigational Site
Tacoma, Washington, United States, 98418
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: LPL112498
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: LPL112498
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: LPL112498
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: LPL112498
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: LPL112498
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: LPL112498
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: LPL112498
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00743860     History of Changes
Other Study ID Numbers: LPL112498 
Study First Received: August 28, 2008
Last Updated: November 15, 2016
Individual Participant Data  
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.

Keywords provided by GlaxoSmithKline:
darapladib
pharmacokinetics
metabolite
SB-480848

Additional relevant MeSH terms:
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Darapladib
Phospholipase A2 Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on January 19, 2017