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

NCT01675973 | Terminated Phase 1

• 1 other identifier: GS-US-259-0112
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Severe Renal Impairment

Keywords

Ranolazine; renal impairment

Outcome Measures

Primary Outcomes (1)

• 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)

  * 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) \[Time frame: 0, 1, 2, 3, 4, 6, 8, 10, and 12 hours post-dose on Day 7 for Cohort A and Days -1 and 7 for Cohort B\]

  Day 7 for Cohorts A & B, and Day -1 for Cohort B only.

Secondary Outcomes (1)

• Number of subjects with AEs

  From Day -5 for Cohort B or Day 1 for Cohort A through the 14-day follow-up.

Study Arms (2)

Subjects with severe renal impairment

EXPERIMENTAL

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

Drug: RANEXA

Subjects with normal renal function

EXPERIMENTAL

Cohort A (healthy subjects with normal renal function): Approximately 10 subjects will be enrolled to obtain approximately 8 evaluable subjects.

Drug: RANEXA

Interventions

RANEXA DRUG

500mg BID up to 1000mg BID

Subjects with normal renal function; Subjects with severe renal impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (1)

Clinical Pharmacology of Miami

Miami, Florida, 33014, United States

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Ranolazine

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2012
• First Posted: August 30, 2012
• Study Start: July 1, 2012
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: December 6, 2012

Record last verified: 2012-12

Locations

US (1)