Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients - Full Text View

Purpose

End-stage renal disease (ESRD) patients often develop cardiovascular complications, and cardiovascular disease is the leading cause of death in this population. Ranolazine's ability to treat angina without reducing heart rate or blood pressure makes it an important option for ESRD patients. The hemodialysis clearance of ranolazine is unknown. A single-dose pharmacokinetic study is needed to characterize ranolazine and its metabolites in ESRD patients on and off hemodialysis. Results of the proposed study will provide initial dosing estimates for a follow-up, multiple-dose pharmacokinetic study in this population.

Condition	Intervention	Phase
End-stage Renal Disease Cardiovascular Disease	Drug: Ranolazine Procedure: Pharmacokinetic Blood and Dialysate Sampling Procedure: QT Interval	Phase 4


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients

Resource links provided by NLM:

MedlinePlus related topics: Dialysis

Drug Information available for: Ranolazine

U.S. FDA Resources

Further study details as provided by Bruce A. Mueller, University of Michigan:

Primary Outcome Measures:

Pharmacokinetic Parameters of Ranolazine [ Time Frame: At hours post-dose: 0, 2, 4, 8, 12, 15, 18, 20, 22, 23, 26, 30, 65 ]
Peak Plasma Concentration (Cmax) with a 500 mg dose of ranolazine

Secondary Outcome Measures:

QT Interval [ Time Frame: At hours post-dose: 0, 2, 4, 8, 12, 15, 18, 20, 22, 23, 26, 30 ]
Calculation of the QT interval after receiving a single-dose of ranolazine


Enrollment:	17
Study Start Date:	October 2011
Study Completion Date:	March 2013
Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Ranolazine End-stage renal disease patients receiving a single-dose of ranolazine and a concomitant hemodialysis session.	Drug: Ranolazine A single dose of two oral ranolazine extended release 500 mg tablets Other Name: Ranexa Procedure: Pharmacokinetic Blood and Dialysate Sampling Blood samples collected to assess ranolazine plasma and dialysate concentrations. Other Names: Ranexa PK sampling Procedure: QT Interval Calculation of a QT interval will be performed throughout subject participation. Other Names: Ranexa QT interval calculation

Arms

Assigned Interventions

Experimental: Ranolazine

End-stage renal disease patients receiving a single-dose of ranolazine and a concomitant hemodialysis session.

Drug: Ranolazine

A single dose of two oral ranolazine extended release 500 mg tablets

Other Name: Ranexa

Procedure: Pharmacokinetic Blood and Dialysate Sampling

Blood samples collected to assess ranolazine plasma and dialysate concentrations.

Other Names:

Ranexa
PK sampling

Procedure: QT Interval

Calculation of a QT interval will be performed throughout subject participation.

Other Names:

Ranexa
QT interval calculation

Eligibility


Ages Eligible for Study:	18 Years to 74 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

18-74 years of age
Within 50% of ideal body weight and greater than 40 kg
Chronic kidney disease (CKD) stage 5 receiving maintenance hemodialysis for at least 3 months
Native kidney estimated glomerular filtration rate(GFR) < 10 mL/min
No concurrent illness or evidence of infection
Able to give informed consent

Exclusion Criteria:

QTc interval > 470 msec at echocardiogram (ECG) obtained within the last 6 months
Concomitant QT-prolonging drugs, major P-gp inhibitors, and CYP3A4 inducers and inhibitors including: cyclosporine, rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, St. John's Wort, ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, saquinavir, quinidine, dofetilide, sotalol, amiodarone, erythromycin, thioridazine, ziprasidone, haloperidol, trimethoprim/sulfamethoxazole, ciprofloxacin, norfloxacin, levofloxacin, moxifloxacin
Pre-study hemoglobin < 9.5 g/dL
Plasma albumin < 2.5 g/dL
Liver disease - exclude subjects with a Child Pugh score of C or higher
Positive pregnancy test
Breastfeeding
Allergy to ranolazine
Participating in another investigational study
Hepatitis B infection due to dialysis isolation requirements
Unstable blood pressure control
Need for routine large fluid removal during dialysis (> 4L)

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01435174

Locations


United States, Michigan
University of Michigan Hospital
Ann Arbor, Michigan, United States, 48109

Sponsors and Collaborators

University of Michigan

Gilead Sciences

Investigators


Principal Investigator:	Bruce A Mueller, PharmD	University of Michigan

More Information


Responsible Party:	Bruce A. Mueller, Associate Dean of Academic Affairs, University of Michigan
ClinicalTrials.gov Identifier:	NCT01435174 History of Changes
Other Study ID Numbers:	IN-US-259-0123, HUM00051141
Study First Received:	September 14, 2011
Results First Received:	May 21, 2014
Last Updated:	June 24, 2014

Keywords provided by Bruce A. Mueller, University of Michigan:


ranolazine end-stage renal disease pharmacokinetics cardiovascular disease

Additional relevant MeSH terms:


Cardiovascular Diseases Kidney Diseases Kidney Failure, Chronic Renal Insufficiency, Chronic Urologic Diseases Renal Insufficiency	Dialysis Solutions Ranolazine Pharmaceutical Solutions Sodium Channel Blockers Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2017