Study to Evaluate Darapladib in Moderately Hepatically Impaired Subjects

NCT01154114 | Completed Phase 1

• 1 other identifier: 480848/028
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine any differences in pharmacokinetic parameters of darapladib when dosed to people with moderate liver disease as compared to when dosed in normal healthy volunteers.

Conditions

Atherosclerosis

Keywords

healthy volunteer; hepatic impairment; darapladib; atherosclerosis

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetic endpoints will include darapladib AUC (0-τ), Cmax and Tmax. Metabolites pharmacokinetic parameters AUC (0-τ), Cmax and Tmax will be evaluated as data permit.

  After 10 days of repeat dosing

• Clinical safety data (spontaneous AE reporting, vital signs, nursing/physician observation, and clinical laboratory tests) will be the primary safety endpoint

  Over 10 days of repeat dosing

Study Arms (2)

moderate hepatic impaired subjects

EXPERIMENTAL

Male and female subjects with moderate hepatic impairment defined by a Child-Pugh score of 7-9 will be included. The subjects will be administered 40 mg oral doses of darapladib (SB-480848) enteric-coated tablets daily for 10 consecutive days.

Drug: darapladib

normal healthy volunteers

EXPERIMENTAL

Healthy male and female subjects will be included and will be matched as closely as possible to the group of moderate hepatic impairment subjects for gender, age and body mass index. Each subject will receive daily 40 mg oral doses of darapladib (SB-480848) enteric-coated tablets for 10 consecutive days.

Drug: darapladib

Interventions

darapladib DRUG

darapladib 40 mg oral dose

moderate hepatic impaired subjects; normal healthy volunteers

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A male or female is eligible to enter and participate in this study if he/she is a healthy subject OR a moderately hepatically impaired subject with a Child-Pugh score of 7-9.
• Age between 18 and 65 years inclusive, at the time of signing the informed consent.
• Body mass index (BMI) within the range of 19-37kg/m2
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• QTcB \< 480 msec in all subjects, including those with bundle branch block at screening ECG
• Healthy subjects only: AST, ALT, alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated bilirubin greater than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%)

You may not qualify if:

• Hepatically Impaired Group:
• A positive pre-study drug/alcohol screen, except where subject has prescription for pain or anxiolytic medication that would cause positive test.
• Subjects using any concurrent prohibited medication, and/or receiving concurrent therapy that cannot be safely discontinued and is not approved by the investigator
• 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.
• Consumption of grapefruit or grapefruit juice \> 8oz within 7 days prior to first dose of study medication.
• Currently receiving oral or injectable strong CYP3A4 inhibitor(s)
• Subjects with any predisposing condition including malabsorption syndromes that might interfere with the absorption, distribution, metabolism, or excretion of drugs (except for hepatic impairment) or any previous gastrointestinal (GI) surgery (except appendectomy or gall bladder removal more than three months prior to the study).
• 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 medical monitor, contraindicates their participation.
• History of anaphylaxis, or anaphylactoid (resembling anaphylaxis) reactions, or severe allergic responses.
• Subjects with fluctuating or rapidly deteriorating hepatic function. Subjects should be medically stable in the opinion of the principal investigator, evidenced by liver function tests as well as clinical signs and symptoms for 30 days before the study.
• Subjects with advanced ascites (Grade 3) or subjects with moderate or severe encephalopathy (Grade 3 or 4) as judged by the investigator.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Miami, Florida, 33143, United States

Location

GSK Investigational Site

Orlando, Florida, 32809, United States

Location

Related Links

• Results for study 480848/028 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Atherosclerosis

Interventions

darapladib

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2010
• First Posted: June 30, 2010
• Study Start: July 1, 2010
• Primary Completion: October 15, 2010
• Study Completion: October 15, 2010
• Last Updated: July 26, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

US (2)