Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients

Overview

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.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: March 2013

Interventions

  • Drug: Ranolazine
    • A single dose of two oral ranolazine extended release 500 mg tablets
  • Procedure: Pharmacokinetic Blood and Dialysate Sampling
    • Blood samples collected to assess ranolazine plasma and dialysate concentrations.
  • Procedure: QT Interval
    • Calculation of a QT interval will be performed throughout subject participation.

Arms, Groups and Cohorts

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

Clinical Trial Outcome Measures

Primary 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

Participating in This Clinical Trial

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)

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 74 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Michigan
  • Collaborator
    • Gilead Sciences
  • Provider of Information About this Clinical Study
    • Principal Investigator: Bruce A. Mueller, Associate Dean of Academic Affairs – University of Michigan
  • Overall Official(s)
    • Bruce A Mueller, PharmD, Principal Investigator, University of Michigan

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