Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function

NCT ID: NCT02412098

Last Updated: 2019-07-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-19
• Study Completion Date: 2016-04-22

Brief Summary

The primary objective of this study is to evaluate the pharmacokinetic (PK) profile of oral eleclazine and its metabolite, GS-623134, in participants with normal and impaired hepatic function. Participants in the healthy control group will be matched to participants with impaired hepatic function by age (± 5 years), gender, and body mass index (± 10%).

Conditions

Long QT Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Moderate Hepatic Impairment (Cohort 1)

Participants with moderate hepatic impairment and matched healthy controls will receive a single dose of eleclazine 30 mg (5 x 6 mg tablets).

Group Type: EXPERIMENTAL

Eleclazine

Intervention Type: DRUG

Eleclazine tablets administered orally

Severe Hepatic Impairment (Cohort 2)

Participants with severe hepatic impairment and matched healthy controls will receive a single dose of eleclazine 30 mg (5 x 6 mg tablets).

Group Type: EXPERIMENTAL

Eleclazine

Intervention Type: DRUG

Eleclazine tablets administered orally

Mild Hepatic Impairment (Cohort 3)

Participants with mild hepatic impairment and matched healthy controls will receive a single dose of eleclazine 30 mg (5 x 6 mg tablets).

Group Type: EXPERIMENTAL

Eleclazine

Intervention Type: DRUG

Eleclazine tablets administered orally

Interventions

Eleclazine

Eleclazine tablets administered orally

Intervention Type: DRUG

Other Intervention Names

GS-6615

Eligibility Criteria

Inclusion Criteria

All participants:

• Be a nonsmoker or consume < 20 cigarettes per day
• Have a calculated body mass index (BMI) from 18 to 36 kg/m^2, inclusive, at study screening
• Have a creatinine clearance (CrCl) ≥ 60 mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at screening
• Have either a normal 12-lead electrocardiogram (ECG) or one with abnormalities that are considered clinically insignificant by the investigator
• Screening labs within defined thresholds

• Must have diagnosis of chronic (> 6 months), stable hepatic impairment with no clinically significant changes within 3 months (90 days) prior to study drug administration (Day 1)
• Individuals with severe hepatic impairment must have a score on the Child-Pugh-Turcotte scale of 10-15 at screening. If an individual's score changes during the course of the study, the score at screening will be used for classification.
• Individuals with moderate hepatic impairment must have a score on the Child-Pugh-Turcotte scale of 7-9 at screening. If an individual's score changes during the course of the study, the score at Screening will be used for classification.
• Individuals with mild hepatic impairment must have a score on the Child-Pugh-Turcotte scale of 5-6 at screening. If an individual's score changes during the course of the study, the score at screening will be used for classification.

Exclusion Criteria

• Pregnant or lactating females
• History of meningitis or encephalitis, epilepsy, seizures, migraines, tremors, myoclonic jerks, narcolepsy, obstructive sleep apnea, anxiety, syncope, head injuries or a family history of seizures
• Presence or history of cardiovascular disease (including history of myocardial infarction based on ECG and/or clinical history, any history of ventricular tachycardia, congestive heart failure, cardiomyopathy, or left ventricular ejection fraction < 40%), cardiac conduction abnormalities, a family history of Long QT Syndrome, or unexplained death in an otherwise healthy individual between the ages of 1 and 30 years
• Syncope, palpitations, or unexplained dizziness
• Implanted defibrillator or pacemaker
• Are unable to comply with study requirements or are otherwise believed, by the study investigator, to be inappropriate for study participation for any reason

• Active hepatitis B virus (HBV) infection. Individuals who have HBsAg are ineligible
• Requires paracentesis > 1 time per month
• Severe (grade 3 or 4) encephalopathy as judged by the investigator
• History of gastric or esophageal variceal bleeding within the past 6 months and for which varices have not been adequately treated with medication and/or surgical procedures

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Miami, Florida, United States

Orlando, Florida, United States

Minneapolis, Minnesota, United States

Kansas City, Missouri, United States

München, , Germany

Auckland, , New Zealand

Bucharest, , Romania

Countries

United States; Germany; New Zealand; Romania

Other Identifiers

2014-005266-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-372-1048

Identifier Type: -

Identifier Source: org_study_id