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

A Study to Evaluate the Pharmacokinetics of the Enteric-Coated Micronized Free Base Formulation of Darapladib [SB-480848] and Its Metabolites in Healthy Volunteers.

This study is designed to assess the pharmacokinetics of darapladib and its metabolites following single and 28 days of repeat dosing of darapladib.

Study Overview

• Status: Completed
• Conditions: Atherosclerosis
• Intervention / Treatment: Drug: darapladib

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Tacoma, Washington, United States, 98418
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single dose; single oral dose	Drug: darapladib; experimental drug
Experimental: Repeat Dose; 28 day repeat dose	Drug: darapladib; experimental drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	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.	throughout study

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: August 28, 2008
• First Submitted That Met QC Criteria: August 28, 2008
• First Posted (Estimate): August 29, 2008

Study Record Updates

• Last Update Posted (Estimate): November 16, 2016
• Last Update Submitted That Met QC Criteria: November 15, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: pharmacokinetics; metabolite; SB-480848; darapladib
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Phospholipase A2 Inhibitors; Darapladib
• Other Study ID Numbers: LPL112498

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. Individual Participant Data Set
   Information identifier: LPL112498
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Dataset Specification
   Information identifier: LPL112498
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Statistical Analysis Plan
   Information identifier: LPL112498
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: LPL112498
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: LPL112498
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Annotated Case Report Form
   Information identifier: LPL112498
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Informed Consent Form
   Information identifier: LPL112498
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register