Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients

University of Michigan

Status and phase: Completed; Phase 4

Conditions: End-stage Renal Disease; Cardiovascular Disease

Treatments: Drug: Ranolazine; Procedure: Pharmacokinetic Blood and Dialysate Sampling; Procedure: QT Interval

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01435174

IN-US-259-0123, HUM00051141

Details and patient eligibility

About

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.

Enrollment: 17 patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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17 participants in 1 patient group

Ranolazine

Experimental group

Description:

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

Treatment:

Procedure: QT Interval

Procedure: Pharmacokinetic Blood and Dialysate Sampling

Drug: Ranolazine