Back to resultsPharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
Primary Purpose
Long QT Syndrome
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Eleclazine
Sponsored by
About this trial
This is an interventional treatment trial for Long QT Syndrome focused on measuring Hepatic Impairment
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Moderate Hepatic Impairment (Cohort 1)
Severe Hepatic Impairment (Cohort 2)
Mild Hepatic Impairment (Cohort 3)
Arm Description
Participants with moderate hepatic impairment and matched healthy controls will receive a single dose of eleclazine 30 mg (5 x 6 mg tablets).
Participants with severe hepatic impairment and matched healthy controls will receive a single dose of eleclazine 30 mg (5 x 6 mg tablets).
Participants with mild hepatic impairment and matched healthy controls will receive a single dose of eleclazine 30 mg (5 x 6 mg tablets).
Outcomes
Primary Outcome Measures
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).
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).
PK Parameter: Cmax of Eleclazine
Cmax was defined as the maximum observed concentration of drug in plasma.
PK Parameter: Cmax of GS-623134 (Metabolite of Eleclazine)
Cmax was defined as the maximum observed concentration of drug in plasma.
Secondary Outcome Measures
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02412098
Brief Title
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
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
March 19, 2015 (Actual)
Primary Completion Date
April 22, 2016 (Actual)
Study Completion Date
April 22, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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%).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Long QT Syndrome
Keywords
Hepatic Impairment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Moderate Hepatic Impairment (Cohort 1)
Arm Type
Experimental
Arm Description
Participants with moderate hepatic impairment and matched healthy controls will receive a single dose of eleclazine 30 mg (5 x 6 mg tablets).
Arm Title
Severe Hepatic Impairment (Cohort 2)
Arm Type
Experimental
Arm Description
Participants with severe hepatic impairment and matched healthy controls will receive a single dose of eleclazine 30 mg (5 x 6 mg tablets).
Arm Title
Mild Hepatic Impairment (Cohort 3)
Arm Type
Experimental
Arm Description
Participants with mild hepatic impairment and matched healthy controls will receive a single dose of eleclazine 30 mg (5 x 6 mg tablets).
Intervention Type
Drug
Intervention Name(s)
Eleclazine
Other Intervention Name(s)
GS-6615
Intervention Description
Eleclazine tablets administered orally
Primary Outcome Measure Information:
Title
PK (Pharmacokinetic) Parameter: AUCinf of Eleclazine
Description
AUCinf was defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time).
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
Title
PK Parameter: AUCinf of GS-623134 (Metabolite of Eleclazine)
Description
AUCinf was defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time).
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
Title
PK Parameter: Cmax of Eleclazine
Description
Cmax was defined as the maximum observed concentration of drug in plasma.
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
Title
PK Parameter: Cmax of GS-623134 (Metabolite of Eleclazine)
Description
Cmax was defined as the maximum observed concentration of drug in plasma.
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 Measure Information:
Title
Number of Participants Experiencing Treatment-Emergent Adverse Events
Description
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.
Time Frame
First dose date up to 31 days
Title
Number of Participants Experiencing Clinical Laboratory Abnormalities
Description
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.
Time Frame
First dose date up to 31 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
Miami
State/Province
Florida
Country
United States
City
Orlando
State/Province
Florida
Country
United States
City
Minneapolis
State/Province
Minnesota
Country
United States
City
Kansas City
State/Province
Missouri
Country
United States
City
München
Country
Germany
City
Auckland
Country
New Zealand
City
Bucharest
Country
Romania
12. IPD Sharing Statement
Learn more about this trial
Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
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