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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 55
- 主要终点
- Plasma pharmacokinetics (PK) profiles of eleclazine and its metabolite GS-623134: AUC_0-inf and Cmax
研究概览
简要总结
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%).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
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).
干预措施: Eleclazine (Drug)
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).
干预措施: Eleclazine (Drug)
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).
干预措施: Eleclazine (Drug)
结局指标
主要结局
Plasma pharmacokinetics (PK) profiles of eleclazine and its metabolite GS-623134: AUC_0-inf and Cmax
时间窗: 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
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.
次要结局
- Safety profile of eleclazine as measured by incidence of adverse events and laboratory abnormalities(Up to 58 days)