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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02412098




Registration number
NCT02412098
Ethics application status
Date submitted
11/03/2015
Date registered
8/04/2015
Date last updated
29/07/2019

Titles & IDs
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
Secondary ID [1] 0 0
2014-005266-30
Secondary ID [2] 0 0
GS-US-372-1048
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Long QT Syndrome 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Eleclazine

Experimental: 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).

Experimental: 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).

Experimental: 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).


Treatment: Drugs: Eleclazine
Eleclazine tablets administered orally

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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).
Timepoint [1] 0 0
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
Primary outcome [2] 0 0
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).
Timepoint [2] 0 0
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
Primary outcome [3] 0 0
PK Parameter: Cmax of Eleclazine - Cmax was defined as the maximum observed concentration of drug in plasma.
Timepoint [3] 0 0
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
Primary outcome [4] 0 0
PK Parameter: Cmax of GS-623134 (Metabolite of Eleclazine) - Cmax was defined as the maximum observed concentration of drug in plasma.
Timepoint [4] 0 0
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 [1] 0 0
Number of Participants Experiencing Treatment-Emergent Adverse Events - Treatment-emergent adverse events (AEs) are defined as one or both of the following:
Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug.
Any AEs leading to premature discontinuation of study drug.
Timepoint [1] 0 0
First dose date up to 31 days
Secondary outcome [2] 0 0
Number of Participants Experiencing Clinical Laboratory Abnormalities - Treatment-emergent laboratory abnormalities reported as an adverse event (AE) or serious adverse event (SAE) are presented. Laboratory abnormalities that required medical or surgical intervention or led to study drug interruption, modification, or discontinuation were recorded as an AE or SAE, as applicable, and are reported here. Laboratory abnormalities without clinical significance were not recorded as AEs or SAEs and therefore, are not being reported.
Timepoint [2] 0 0
First dose date up to 31 days

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Minnesota
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
Germany
State/province [4] 0 0
München
Country [5] 0 0
New Zealand
State/province [5] 0 0
Auckland
Country [6] 0 0
Romania
State/province [6] 0 0
Bucharest

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
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%).
Trial website
https://clinicaltrials.gov/show/NCT02412098
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications