Clinical trial NCT00743860: A Healthy Volunteer Pharmacokinetic Study of Single and Repeat Doses of SB-480848
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Atherosclerosis
Keywords: darapladib
pharmacokinetics
metabolite
SB-480848
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-08-29
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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.

Primary outcomes:
measure: 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.
timeFrame: following single and 28 day repeat dose
measure: Clinical safety data (spontaneous AE reporting, vital signs, nursing/physician observation, and clinical laboratory tests) will be the primary safety endpoint.
timeFrame: throughout study
Secondary outcomes:
measure: Secondary PK endpoints will include Tmax and T½ of darapladib and its metabolites (M10, M3 and M4) as data permit.
timeFrame: following single and 28 day repeat dose
measure: Plasma Lp-PLA2 activity, expressed in terms of percent inhibition relative to baseline, as data permit.
timeFrame: following single and repeat dose
Other outcomes:
Locations:
city: Tacoma
country: United States
facility: GSK Investigational Site
state: Washington
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: