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

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-

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

Study Overview

• Status: Completed
• Conditions: Atherosclerosis
• Intervention / Treatment: Drug: SB-480848 (Darapladib)

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Ibaraki, Japan, 305-0856
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 64 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Safety/tolerability of repeat oral doses of darapladib
Primary Pharmacokinetic parameters of repeat oral doses of darapladib

Secondary Outcome Measures

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

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: January 1, 2008
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: February 13, 2008
• First Submitted That Met QC Criteria: February 22, 2008
• First Posted (Estimate): February 25, 2008

Study Record Updates

• Last Update Posted (Estimate): November 3, 2016
• Last Update Submitted That Met QC Criteria: November 2, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: SB480848,; Japanese healthy volunteers; 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: LPL110736

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. Statistical Analysis Plan
   Information identifier: LPL110736
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: LPL110736
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: LPL110736
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Individual Participant Data Set
   Information identifier: LPL110736
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: LPL110736
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: LPL110736
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Annotated Case Report Form
   Information identifier: LPL110736
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register