Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02412098
• Date of registration: 11/03/2015
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences
• Public title: Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
• Scientific 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
• Date of first enrolment: March 19, 2015
• Target sample size: 49
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02412098
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Germany, Moldova, Republic of, New Zealand, Romania, United States

Contacts

• Name: Gilead Study Director
• Affiliation: Gilead Sciences

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Long QT Syndrome

Intervention(s)

Drug: Eleclazine

Primary Outcome(s)

PK Parameter: Cmax of Eleclazine [Time Frame: 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) [Time Frame: 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 (Pharmacokinetic) Parameter: AUCinf of Eleclazine [Time Frame: 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) [Time Frame: 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 Outcome(s)

Number of Participants Experiencing Treatment-Emergent Adverse Events [Time Frame: First dose date up to 31 days]

Number of Participants Experiencing Clinical Laboratory Abnormalities [Time Frame: First dose date up to 31 days]

Secondary ID(s)

2014-005266-30

GS-US-372-1048

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 29/07/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02412098