Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function

A Phase 1 Open-Label, Parallel-Group, Adaptive, Single Dose Study to Evaluate the Pharmacokinetics of GS-6615 in Subjects With Normal and Impaired Renal Function

This study will evaluate the pharmacokinetics (PK), safety, and tolerability of a single oral dose of eleclazine and its metabolite, GS-623134, in participants with normal and impaired renal function. Participants in the healthy control group will be matched to participants with impaired renal function by age (± 5 years), gender, and body mass index (± 10%).

Study Overview

• Status: Completed
• Conditions: Long QT Syndrome
• Intervention / Treatment: Drug: Eleclazine

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 1

Contacts and Locations

Study Locations

• Moldova, Republic of
  • Chisinau, Moldova, Republic of
• Romania
  • Bucharest, Romania
• United States
  • Florida
    • DeLand, Florida, United States
    • Miami, Florida, United States
    • Orlando, Florida, United States
  • Minnesota
    • St. Paul, Minnesota, United States
  • Missouri
    • Kansas City, Missouri, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All Individuals:

• 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 either a normal 12-lead electrocardiogram (ECG) or one with abnormalities that are considered clinically insignificant by the investigator
• Screening labs within defined thresholds

Individuals with mild, moderate, or severe renal impairment must also meet the following additional inclusion criteria to be eligible for participation in this study:

• Must have diagnosis of chronic (> 6 months), stable renal impairment with no clinically significant changes within 3 months (90 days) prior to study drug administration (Day 1)
• Individuals with severe renal impairment, creatinine clearance (CLcr) must be 15-29 mL/min, inclusive (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at the screening evaluation. If an individual's score changes during the course of the study, the score at screening will be used for classification.
• Individuals with moderate renal impairment, CLcr must be 30-59 mL/min, inclusive (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at the screening evaluation. If an individual's score changes during the course of the study, the score at screening will be used for classification.
• Individuals with mild renal impairment , CLcr must be 60-89, inclusive mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at the screening evaluation. If an individual's score changes during the course of the study, the score at screening will be used for classification.

Individuals with normal renal function must also meet the following additional inclusion criteria to be eligible for participation in this study:

• Must, in the opinion of the Investigator, be in good health based upon medical history, physical examination, vital signs, and screening laboratory evaluations
• Must have an CLcr of ≥ 90 mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at the screening evaluation.

Exclusion Criteria:

• 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
• Medical history of renal carcinoma or hepatorenal syndrome.
• Individuals receiving or anticipating use of hemodialysis, peritoneal dialysis, or any other renal replacement therapy or other medical procedure that serves as a surrogate for renal function during the study.
• Individuals with fluctuating or rapidly deteriorating renal function. Assessment of the stability of the individual's renal function will be determined by the investigator.
• Renal allograft recipients
• Experienced hypertensive crisis, required the addition of ≥1 antihypertensive drug, or required more intensive antihypertensive therapy (eg, addition of a new drug class) in the last 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mild Renal Impairment (CLcr 60-89 mL/min); Participants with mild renal impairment and matched control participants with normal renal function will receive a single dose of eleclazine 30 mg (5 x 6 mg tablets).	Drug: Eleclazine; Eleclazine tablets administered orally in morning with food; Other Names: GS-6615
Experimental: Moderate Renal Impairment (CLcr 30-59 mL/min); Participants with moderate impairment and matched control participants with normal renal function will receive a single dose of eleclazine 30 mg (5 x 6 mg tablets).	Drug: Eleclazine; Eleclazine tablets administered orally in morning with food; Other Names: GS-6615
Experimental: Severe Renal Impairment (CLcr 15-29 mL/min); Participants with severe renal impairment and matched control participants with normal renal function will receive a single dose of eleclazine 30 mg (5 x 6 mg tablets).	Drug: Eleclazine; Eleclazine tablets administered orally in morning with food; Other Names: GS-6615

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma pharmacokinetics (PK) profiles of eleclazine and its metabolite GS-623134: AUC_0-inf and Cmax	This endpoint will measure the plasma PK profiles of eleclazine and GS-623134. PK parameters that will be measured include AUC_0-inf and Cmax.	Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 14, 24, 36, 48, 72, 96, 120 hours, 15, 29, 43, and 57 days postdose on Day 1

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety profile of eleclazine as measured by incidence of adverse events and laboratory abnormalities	Up to 58 days

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: May 8, 2015
• First Submitted That Met QC Criteria: May 8, 2015
• First Posted (Estimate): May 12, 2015

Study Record Updates

• Last Update Posted (Estimate): December 22, 2015
• Last Update Submitted That Met QC Criteria: December 18, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Renal Impairment
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Congenital Abnormalities; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Renal Insufficiency; Long QT Syndrome
• Other Study ID Numbers: GS-US-372-1589; 2014-005267-32 (EudraCT Number)