Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function

NCT ID: NCT02441829

Last Updated: 2015-12-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2015-12-31

Brief Summary

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%).

Conditions

Long QT Syndrome

Keywords

Renal Impairment

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Eleclazine

Intervention Type: DRUG

Eleclazine tablets administered orally in morning with food

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).

Group Type: EXPERIMENTAL

Eleclazine

Intervention Type: DRUG

Eleclazine tablets administered orally in morning with food

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).

Group Type: EXPERIMENTAL

Eleclazine

Intervention Type: DRUG

Eleclazine tablets administered orally in morning with food

Interventions

Eleclazine

Eleclazine tablets administered orally in morning with food

Intervention Type: DRUG

Other Intervention Names

GS-6615

Eligibility Criteria

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

• 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.

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brian McNabb, MD

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

DeLand, Florida, United States

Miami, Florida, United States

Orlando, Florida, United States

Saint Paul, Minnesota, United States

Kansas City, Missouri, United States

Chisinau, , Moldova

Bucharest, , Romania

Countries

United States; Moldova; Romania

Other Identifiers

2014-005267-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-372-1589

Identifier Type: -

Identifier Source: org_study_id