Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients
Condition: End-stage Renal Disease; Cardiovascular Disease
MeSH terms: Kidney Diseases; Kidney Failure, Chronic; Cardiovascular Diseases
Intervention: Ranolazine; Pharmacokinetic Blood and Dialysate Sampling; QT Interval
Intervention description: A single dose of two oral ranolazine extended release 500 mg tablets; Blood samples collected to assess ranolazine plasma and dialysate concentrations.; Calculation of a QT interval will be performed throughout subject participation.
Intervention MeSH terms: Ranolazine; Dialysis Solutions
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Maximum age: 74 Years
Healthy volunteers: No
Keywords: ranolazine; end-stage renal disease; pharmacokinetics; cardiovascular disease

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.
    

Eligibility 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)