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

Atherosclerosis Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00743860
• Other study ID #: LPL112498
• Status: Completed
• Phase: Phase 1
• First received: August 28, 2008
• Last updated: November 15, 2016
• Start date: September 2008
• Est. completion date: December 2008

Study information

• Verified date: November 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atherosclerosis

Intervention

Drug:
• darapladib
experimental drug

Locations

Country	Name	City	State
United States	GSK Investigational Site	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	Clinical safety data (spontaneous AE reporting, vital signs, nursing/physician observation, and clinical laboratory tests) will be the primary safety endpoint.		throughout study	No
Secondary	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	No
Secondary	Plasma Lp-PLA2 activity, expressed in terms of percent inhibition relative to baseline, as data permit.		following single and repeat dose	No

External Links

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