Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function

NCT02441829 | Completed Phase 1

• 2 other identifiers: GS-US-372-15892014-005267-32
• Study Type: interventional
• Target: 55
• Locations: 3 countries
• Sites: 7

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Safety profile of eleclazine as measured by incidence of adverse events and laboratory abnormalities

  Up to 58 days

Study Arms (3)

Mild Renal Impairment (CLcr 60-89 mL/min)

EXPERIMENTAL

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

Moderate Renal Impairment (CLcr 30-59 mL/min)

EXPERIMENTAL

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

Severe Renal Impairment (CLcr 15-29 mL/min)

EXPERIMENTAL

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

Interventions

Eleclazine DRUG

Eleclazine tablets administered orally in morning with food

Also known as: GS-6615

Mild Renal Impairment (CLcr 60-89 mL/min); Moderate Renal Impairment (CLcr 30-59 mL/min); Severe Renal Impairment (CLcr 15-29 mL/min)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (7)

Unknown Facility

DeLand, Florida, United States

Location

Unknown Facility

Miami, Florida, United States

Location

Unknown Facility

Orlando, Florida, United States

Location

Unknown Facility

Saint Paul, Minnesota, United States

Location

Unknown Facility

Kansas City, Missouri, United States

Location

Unknown Facility

Chisinau, Moldova

Location

Unknown Facility

Bucharest, Romania

Location

MeSH Terms

Conditions

Long QT Syndrome; Renal Insufficiency

Interventions

eleclazine

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Brian McNabb, MD

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2015
• First Posted: May 12, 2015
• Study Start: May 1, 2015
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 22, 2015

Record last verified: 2015-12

Locations

MO (1); US (5); RO (1)