A Phase 1 Study to Assess the Effect of Severe Renal Impairment on the Pharmacokinetics, as Well as Safety/Tolerability, of Ranolazine

NCT ID: NCT01675973

Last Updated: 2012-12-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2012-08-31

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.

Conditions

Severe Renal Impairment

Keywords

Ranolazine; renal impairment

Study Design

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

Study Groups

Subjects with severe renal impairment

Cohort B (subjects with severe RI): Approximately 10 subjects will be enrolled to obtain approximately 8 evaluable subjects.

Group Type: EXPERIMENTAL

RANEXA

Intervention Type: DRUG

500mg BID up to 1000mg BID

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.

Group Type: EXPERIMENTAL

RANEXA

Intervention Type: DRUG

500mg BID up to 1000mg BID

Interventions

RANEXA

500mg BID up to 1000mg BID

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Males and females, 18 to 75 years old, inclusive
• Body mass index (BMI) 18 to 40 kg/m2, inclusive, at Screening
• Females of child-bearing potential must have a negative pregnancy test at Screening and on Day -1 (Cohort A) or Day -6 (Cohort B) and must agree to use highly effective contraception methods from Screening throughout the duration of the Treatment Period and for 14 days following the last dose of study drug

• Estimated creatinine clearance (CLCR), according to the Cockcroft-Gault (C-G) equation, ≥ 90 mL/min at Screening
• Age, BMI, and sex comparable to those of subjects of Cohort B
• Good health status as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations

• Diagnosis of CKD
• Estimated glomerular filtration rate (eGFR), according to the Modification of Diet in Renal Disease (MDRD) equation, < 30 mL/min/1.73 m2 (and not receiving dialysis)
• Stable medication dose and dosing regimen for treatment of the complications of renal disease or other concomitant chronic illnesses for at least 2 weeks prior to study drug administration

Exclusion Criteria

• 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

• 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

• 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

• 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

Locations

Clinical Pharmacology of Miami

Miami, Florida, United States

Countries

United States

Other Identifiers

GS-US-259-0112

Identifier Type: -

Identifier Source: org_study_id