A Phase 1, Parallel-group, Open-label, Multiple-dose Study to Assess the Pharmacokinetics, Safety, and Tolerability of Ranolazine ER in Subjects With Severe Renal Impairment as Compared to Healthy Subjects With Normal Renal Function
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Area under the plasma concentration vs time curve over the dosing interval at steady state (AUCtau) and Maximum observed plasma concentration at steady-state (Cmax)
研究概览
简要总结
The purpose of this study is to assess the effect of severe renal impairment on the steady-state PK, as well as safety and tolerability, of ranolazine, compared to subjects with normal renal function.
详细描述
The primary objective of this study is to assess the effects of severe renal impairment (RI) on the steady-state pharmacokinetics (PK) of ranolazine and key metabolites. The secondary objective of this study is to assess the safety and tolerability of multiple oral doses of ranolazine in subjects with severe RI.
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
- 未提供
排除标准
- •Exclusion criteria (All Cohorts):
- •History of uncontrolled or unstable cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematopoietic, psychiatric, and/or neurological disease
- •Current or recent (within 3 months) gastrointestinal (GI) disease or any GI surgery that could impact absorption of study drug
- •Any major surgery within 4 weeks of dosing with study drug
- •Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within 4 weeks of dosing with study drug
- •Blood transfusion within 4 weeks of dosing with study drug
- •Consumption of > 14 alcoholic drinks per week, or more than 4 alcoholic drinks on any one day
- •History of regular use of tobacco- or nicotine-containing products in excess of 10 cigarettes per day or equivalent
- •History of substance abuse within 12 months prior to Screening
- •Positive drug screen
- •Positive alcohol test
- •Clinically significant history of hepatic disease
- •QTcF interval > 480 msec at Screening or Day -6 (for Cohort B) or Day -1 (for Cohort A)
- •History of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmia, or torsade de pointes
- •Known hypersensitivity or previous intolerance to ranolazine or any of its excipients
- •Treatment with selected medications
- •Pregnancy or lactation
- •Other condition(s) that, in the opinion of the Investigator, would prevent compliance with the study protocol
- •Exclusion criteria (Cohort A [Healthy subjects with normal renal function] only):
- •Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG, or clinical laboratory determinations
- •Hemoglobin < 12 g/dL for males, < 11 g/dL for females at Screening
- •Any prescription and over-the-counter medications, including herbal products
- •Exclusion criteria (Cohort B, Severe RI):
- •Any clinical, ECG, and laboratory findings beyond those which are consistent with the degree of renal dysfunction
- •History of or anticipated near-term need for renal transplant (within 3 months)
- •History of hemodialysis or peritoneal dialysis within 1 year prior to Screening, or anticipated need for hemodialysis or peritoneal dialysis during the study
- •History of acute renal failure or nephrotic syndrome within 1 year prior to Screening
- •History of diabetic ketoacidosis
- •History of severe hypoglycemia
- •Other condition(s) that, in the opinion of the Investigator, would prevent compliance with the study protocol
研究组 & 干预措施
Subjects with severe renal impairment
Cohort B (subjects with severe RI): Approximately 10 subjects will be enrolled to obtain approximately 8 evaluable subjects.
干预措施: RANEXA (Drug)
Subjects with normal renal function
Cohort A (healthy subjects with normal renal function): Approximately 10 subjects will be enrolled to obtain approximately 8 evaluable subjects.
干预措施: RANEXA (Drug)
结局指标
主要结局
Area under the plasma concentration vs time curve over the dosing interval at steady state (AUCtau) and Maximum observed plasma concentration at steady-state (Cmax)
时间窗: Day 7 for Cohorts A & B, and Day -1 for Cohort B only.
* Maximum observed plasma ranolazine concentration at steady-state (Cmax) \[Time frame: 0, 1, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 7 for Cohort A and Days -1 and 7 for Cohort B\] * Area under the plasma ranolazine concentration versus time curve over the dosing interval at steady state (AUCtau) \[Time frame: 0, 1, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 7 for Cohort A and Days -1 and 7 for Cohort B\]
次要结局
- Number of subjects with AEs(From Day -5 for Cohort B or Day 1 for Cohort A through the 14-day follow-up.)