Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function

NCT02412098 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: GS-US-372-10482014-005266-30
• Study Type: interventional
• Target: 49
• Locations: 4 countries
• Sites: 7

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

Keywords

Hepatic Impairment

Outcome Measures

Primary Outcomes (4)

• PK (Pharmacokinetic) Parameter: AUCinf of Eleclazine

  AUCinf was defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time).

  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

• PK Parameter: AUCinf of GS-623134 (Metabolite of Eleclazine)

  AUCinf was defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time).

  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

• PK Parameter: Cmax of Eleclazine

  Cmax was defined as the maximum observed concentration of drug in plasma.

  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

• PK Parameter: Cmax of GS-623134 (Metabolite of Eleclazine)

  Cmax was defined as the maximum observed concentration of drug in plasma.

  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 (2)

• Number of Participants Experiencing Treatment-Emergent Adverse Events

  First dose date up to 31 days

• Number of Participants Experiencing Clinical Laboratory Abnormalities

  First dose date up to 31 days

Study Arms (3)

Moderate Hepatic Impairment (Cohort 1)

EXPERIMENTAL

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

Drug: Eleclazine

Severe Hepatic Impairment (Cohort 2)

EXPERIMENTAL

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

Drug: Eleclazine

Mild Hepatic Impairment (Cohort 3)

EXPERIMENTAL

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

Drug: Eleclazine

Interventions

Eleclazine DRUG

Eleclazine tablets administered orally

Also known as: GS-6615

Mild Hepatic Impairment (Cohort 3); Moderate Hepatic Impairment (Cohort 1); Severe Hepatic Impairment (Cohort 2)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (7)

Unknown Facility

Miami, Florida, United States

Location

Unknown Facility

Orlando, Florida, United States

Location

Unknown Facility

Minneapolis, Minnesota, United States

Location

Unknown Facility

Kansas City, Missouri, United States

Location

Unknown Facility

München, Germany

Location

Unknown Facility

Auckland, New Zealand

Location

Unknown Facility

Bucharest, Romania

Location

MeSH Terms

Conditions

Long QT Syndrome

Interventions

eleclazine

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: March 11, 2015
• First Posted: April 8, 2015
• Study Start: March 19, 2015
• Primary Completion: April 22, 2016
• Study Completion: April 22, 2016
• Last Updated: July 29, 2019
• Results First Posted: July 29, 2019

Record last verified: 2019-05

Locations

NZ (1); US (4); DE (1); RO (1)