Clinical trial NCT00622830: Phase I Study of SB-480848(Darapladib) -Repeat Dose Study in Healthy Japanese Male Subjects-
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-
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Atherosclerosis
Keywords: darapladib,
SB480848,
Japanese healthy volunteers
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-02-25
Enrollment: 18
Sex: MALE
Minimum age (years): 20
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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.

Primary outcomes:
measure: Safety/tolerability of repeat oral doses of darapladib
measure: Primary Pharmacokinetic parameters of repeat oral doses of darapladib
Secondary outcomes:
measure: -Secondary PK parameters
measure: Tmax, and t1/2 of SB-480848 and AUC, Cmax, t1/2 and Tmax of the pharmacologically active metabolite SB-553253 (as data permit)
measure: Plasma Lp-PLA2 activity, expressed in terms of percent inhibition relative to baseline
measure: Estimation of PK/PD parameters and their associated variability, appropriate to the final models
measure: -PK parameters of SB553253
measure: -description of plasma concentration-Lp-PLA2 activity inhibition relationship after repeat oral doses of darapladib. all measured same timepoints as primary
measure: -inhibition of Lp-PLA2 activity
Other outcomes:
Locations:
city: Ibaraki
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: