A Phase 1 Study to Assess the Effect of Severe Renal Impairment on the Pharmacokinetics, as Well as Safety/Tolerability, of Ranolazine
- Registration Number
- NCT01675973
- Lead Sponsor
- Gilead Sciences
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 4
Not provided
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Subjects with normal renal function RANEXA Cohort A (healthy subjects with normal renal function): Approximately 10 subjects will be enrolled to obtain approximately 8 evaluable subjects. Subjects with severe renal impairment RANEXA Cohort B (subjects with severe RI): Approximately 10 subjects will be enrolled to obtain approximately 8 evaluable subjects.
- Primary Outcome Measures
Name Time Method 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) 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) \[Time frame: 0, 1, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 7 for Cohort A and Days -1 and 7 for Cohort B\]
- Secondary Outcome Measures
Name Time Method Number of subjects with AEs From Day -5 for Cohort B or Day 1 for Cohort A through the 14-day follow-up.
Trial Locations
- Locations (1)
Clinical Pharmacology of Miami
🇺🇸Miami, Florida, United States