Clinical trial NCT02412098: Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
Official title: A Phase 1, Open-Label, Parallel-Group, Adaptive, Single Dose Study to Evaluate the Pharmacokinetics of GS-6615 in Subjects With Normal and Impaired Hepatic Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Long QT Syndrome
Keywords: Hepatic Impairment
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-04-08
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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%).


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

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

Primary outcomes:
measure: PK (Pharmacokinetic) Parameter: AUCinf of Eleclazine
timeFrame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72, 96, 120 hours on Day 1 and approximately the same time in the morning as predose of Day 1 on Days 15, 29, 43, and 57
measure: PK Parameter: AUCinf of GS-623134 (Metabolite of Eleclazine)
timeFrame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72, 96, 120 hours on Day 1 and approximately the same time in the morning as predose of Day 1 on Days 15, 29, 43, and 57
measure: PK Parameter: Cmax of Eleclazine
timeFrame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72, 96, 120 hours on Day 1 and approximately the same time in the morning as predose of Day 1 on Days 15, 29, 43, and 57
measure: PK Parameter: Cmax of GS-623134 (Metabolite of Eleclazine)
timeFrame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72, 96, 120 hours on Day 1 and approximately the same time in the morning as predose of Day 1 on Days 15, 29, 43, and 57
Secondary outcomes:
measure: Number of Participants Experiencing Treatment-Emergent Adverse Events
timeFrame: First dose date up to 31 days
measure: Number of Participants Experiencing Clinical Laboratory Abnormalities
timeFrame: First dose date up to 31 days
Other outcomes:
Locations:
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Minneapolis
country: United States
state: Minnesota
city: Kansas City
country: United States
state: Missouri
city: München
country: Germany
city: Auckland
country: New Zealand
city: Bucharest
country: Romania
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: