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

Sponsor

Gilead Sciences (Industry)

Overall Status

Terminated

CT.gov ID

NCT01675973

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

3.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Severe Renal Impairment	Drug: RANEXA	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

4 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2012

Actual Primary Completion Date :

Aug 1, 2012

Actual Study Completion Date :

Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Subjects with severe renal impairment Cohort B (subjects with severe RI): Approximately 10 subjects will be enrolled to obtain approximately 8 evaluable subjects.	Drug: RANEXA 500mg BID up to 1000mg BID
Experimental: 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.	Drug: RANEXA 500mg BID up to 1000mg BID

Arm

Intervention/Treatment

Experimental: Subjects with severe renal impairment

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

Drug: RANEXA

500mg BID up to 1000mg BID

Experimental: 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.

Drug: RANEXA

500mg BID up to 1000mg BID

Outcome Measures

Primary Outcome Measures

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

Number of subjects with AEs [From Day -5 for Cohort B or Day 1 for Cohort A through the 14-day follow-up.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Pharmacology of Miami	Miami	Florida	United States	33014

Sponsors and Collaborators

Gilead Sciences

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Gilead Sciences

ClinicalTrials.gov Identifier:

NCT01675973

Other Study ID Numbers:

GS-US-259-0112

First Posted:

Aug 30, 2012

Last Update Posted:

Dec 6, 2012

Last Verified:

Dec 1, 2012

Keywords provided by Gilead Sciences

Ranolazine

renal impairment

Additional relevant MeSH terms:

Renal Insufficiency

Ranolazine

Study Results

No Results Posted as of Dec 6, 2012