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

Gilead Sciences

Status and phase

Terminated

Phase 1

Conditions

Severe Renal Impairment

Treatments

Drug: RANEXA

Study type

Interventional

Funder types

Industry

Identifiers

NCT01675973

GS-US-259-0112

Details and patient eligibility

About

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.

Full 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.

Enrollment

4 patients

Sex

All

Ages

18 to 75 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria (All Cohorts):

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

Inclusion criteria (Cohort A [Healthy subjects with normal renal function] only):

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

Inclusion criteria (Cohort B, Severe RI):

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:

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