Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function

Long QT Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02412098
• Other study ID #: GS-US-372-1048
• Secondary ID: 2014-005266-30
• Status: Completed
• Phase: Phase 1
• Start date: March 19, 2015
• Est. completion date: April 22, 2016

Study information

• Verified date: May 2019
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: April 22, 2016
• Est. primary completion date: April 22, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Long QT Syndrome

Intervention

Drug:
• Eleclazine
Eleclazine tablets administered orally

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Germany,  New Zealand,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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.	First dose date up to 31 days
Secondary	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.	First dose date up to 31 days