Phase I Study of SB-480848(Darapladib) -Repeat Dose Study in Healthy Japanese Male Subjects-

Atherosclerosis Clinical Trial

Official title:

Phase I Study of SB-480848 (Darapladib) -A Double Blind, Randomised, Placebo-controlled, Parallel-group, Repeat Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SB-480848 in Healthy Japanese Male Subjects-

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00622830
• Other study ID #: LPL110736
• Status: Completed
• Phase: Phase 1
• First received: February 13, 2008
• Last updated: November 2, 2016
• Start date: January 2008
• Est. completion date: March 2008

Study information

• Verified date: November 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

This study is being conducted to provide safety, tolerability, PK and PD data in repeat dosing that will allow further studies with darapladib in Japanese patients

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: March 2008
• Est. primary completion date: March 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 64 Years

Eligibility

Inclusion criteria:

• Healthy Japanese adult males between 20 and 64 yeas of age, inclusive.

• Healthy subjects are defined as individuals who are free from clinically significant disease as determined by their medical history, physical examination, clinical laboratory examinations, vital sign, 12-lead ECG, immunology tests and urinary drug screen test.

• Bodyweight >50 kg and body mass index (BMI) between 18.5 and 25.0 at screening.

• Subjects must be capable of providing written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

• Baseline QTc interval <450 msec.

• Non-smoker or ex-smoker having ceased smoking for at least 6 months.

• Clinical laboratory examination (AST, ALT, ALP and GGT) at screening are within the normal range.

• The subject is able to attend all visits and complete the study.

Exclusion criteria:

• Any clinically relevant abnormality identified on the screening physical examination, vital sign measurement, 12-lead ECG recording and/or clinical laboratory examination that is deemed by the principal investigator and/or medical monitor to make the subject ineligible for inclusion because of a safety concern.

• History of regular alcohol consumption exceeding, on average, 14 drinks/week for men (1 drink = 5 ounces (150 mL) of wine or 350 mL of beer or 1.5 ounces (45 mL) of 80 proof distilled spirits) within 6 months of screening.

• Positive for urine drug at screening.

• Positive for syphilis, HIV antibody, Hepatitis B surface antigen, Hepatitis C antibody or HTLV-1 antibody at screening.

• Use of prescription or no-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication.

• Consumption of grapefruit juice or food within 7 days prior to the first dose of study medication.

• A history of cholecystectomy or biliary tract disease including a history of liver disease with elevated liver function tests of known or unknown etiology.

• Donation of blood in excess of 400mL within 4 months or 200mL within 1 months prior to at screening.

• History of drug abuse, or current conditions of drug abuse or alcoholism.

• Participation in a clinical study or post-marketing study with an investigational or a non-investigational product or device within 4 months of preceding the first dose of study medication.

• Participation in another clinical study or post-marketing study in which the subject is or will be exposed to an investigational or a non-investigational product or device.

• History of asthma, anaphylaxis or anaphylactoid reactions, severe allergic responses.

• The subject has an allergy for any drug or idiosyncrasy. This excludes a pollen allergy without current symptoms.

• History of sensitivity to heparin or heparin-induced thrombocytopenia.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atherosclerosis

Intervention

Drug:
• SB-480848 (Darapladib)

Locations

Country	Name	City	State
Japan	GSK Investigational Site	Ibaraki

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety/tolerability of repeat oral doses of darapladib
Primary	Primary Pharmacokinetic parameters of repeat oral doses of darapladib
Secondary	-Secondary PK parameters
Secondary	Tmax, and t1/2 of SB-480848 and AUC, Cmax, t1/2 and Tmax of the pharmacologically active metabolite SB-553253 (as data permit)
Secondary	Plasma Lp-PLA2 activity, expressed in terms of percent inhibition relative to baseline
Secondary	Estimation of PK/PD parameters and their associated variability, appropriate to the final models
Secondary	-PK parameters of SB553253
Secondary	-description of plasma concentration-Lp-PLA2 activity inhibition relationship after repeat oral doses of darapladib. all measured same timepoints as primary
Secondary	-inhibition of Lp-PLA2 activity

External Links

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