Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function

Gilead Sciences

Status and phase: Completed; Phase 1

Conditions: Long QT Syndrome

Treatments: Drug: Eleclazine

Study type: Interventional

Funder types: Industry

Identifiers

NCT02412098

2014-005266-30 (EudraCT Number)

GS-US-372-1048

Details and patient eligibility

About

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%).

Enrollment: 49 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Participants with mild, moderate, or severe hepatic impairment must also meet the following additional inclusion criteria:

• 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

Participants with mild, moderate, or severe hepatic impairment must also meet the following additional exclusion criteria:

• 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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49 participants in 3 patient groups

Moderate Hepatic Impairment (Cohort 1)

Experimental group

Description:

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

Treatment:

Drug: Eleclazine

Severe Hepatic Impairment (Cohort 2)

Experimental group

Description:

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

Treatment:

Drug: Eleclazine

Mild Hepatic Impairment (Cohort 3)

Experimental group

Description:

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

Treatment:

Drug: Eleclazine