Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients

• Status: Completed
• Trial end date: 2013-03-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Michigan
• Collaborator: Gilead Sciences
• Treatments: Dialysis Solutions; Ranolazine

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)