Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients

Study Overview
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Brief Summary
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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.

Official Title
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Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients

Conditions
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End-stage Renal Disease, Cardiovascular Disease

Intervention / Treatment
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* Drug: Ranolazine
* Procedure: Pharmacokinetic Blood and Dialysate Sampling
* Procedure: QT Interval


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ranolazine<br>End-stage renal disease patients receiving a single-dose of ranolazine and a concomitant hemodialysis session. | Drug: Ranolazine<br>* A single dose of two oral ranolazine extended release 500 mg tablets<br>* Other names: Ranexa;Procedure: Pharmacokinetic Blood and Dialysate Sampling<br>* Blood samples collected to assess ranolazine plasma and dialysate concentrations.<br>* Other names: PK sampling;Procedure: QT Interval<br>* Calculation of a QT interval will be performed throughout subject participation.<br>* Other names: QT interval calculation;|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ranolazine, end-stage renal disease, pharmacokinetics, cardiovascular disease