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Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients

This study has been completed.
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Bruce A. Mueller, University of Michigan
ClinicalTrials.gov Identifier:
NCT01435174
First received: September 14, 2011
Last updated: March 27, 2013
Last verified: March 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
End-stage Renal Disease
Cardiovascular Disease
 Drug: Ranolazine
Procedure: Pharmacokinetic Blood and Dialysate Sampling
Procedure: QT Interval
 Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients

Resource links provided by NLM:

Drug Information available for: Ranolazine
U.S. FDA Resources

Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Pharmacokinetic parameters of ranolazine [ Time Frame: At hours post-dose: 0, 2, 4, 8, 12, 15, 18, 20, 22, 23, 26, 30, 65 ] [ Designated as safety issue: No ]

    The following pharmacokinetic (PK) parameters will be determined:

    1. Peak Plasma Concentration (Cmax)
    2. Time of peak plasma concentration (Tmax)
    3. Terminal elimination half-life (t1/2)
    4. Volume of distribution
    5. Plasma protein binding
    6. Drug clearance off hemodialysis
    7. Dialytic clearance
    8. Area under the plasma concentration time curve (AUC)


Secondary Outcome Measures:
  • QT interval [ Time Frame: At hours post-dose: 0, 2, 4, 8, 12, 15, 18, 20, 22, 23, 26, 30 ] [ Designated as safety issue: Yes ]
    Calculation of the QT interval after receiving a single-dose of ranolazine


Enrollment: 8
Study Start Date: October 2011
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ranolazine
End-stage renal disease patients receiving a single-dose of ranolazine and a concomitant hemodialysis session.
 Drug: Ranolazine
A single dose of two oral ranolazine extended release 500 mg tablets
Other Name: Ranexa
Procedure: Pharmacokinetic Blood and Dialysate Sampling
Blood samples collected to assess ranolazine plasma and dialysate concentrations.
Other Names:
  • Ranexa
  • PK sampling
Procedure: QT Interval
Calculation of a QT interval will be performed throughout subject participation.
Other Names:
  • Ranexa
  • QT interval calculation

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01435174

Locations
United States, Michigan
University of Michigan Hospital
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan
Gilead Sciences
Investigators
Principal Investigator: Bruce A Mueller, PharmD University of Michigan
  More Information

No publications provided

Responsible Party: Bruce A. Mueller, Associate Dean of Academic Affairs, University of Michigan
ClinicalTrials.gov Identifier: NCT01435174     History of Changes
Other Study ID Numbers: IN-US-259-0123, HUM00051141
Study First Received: September 14, 2011
Last Updated: March 27, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Michigan:
ranolazine
end-stage renal disease
pharmacokinetics
cardiovascular disease

Additional relevant MeSH terms:
Cardiovascular Diseases
Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
 Renal Insufficiency
Ranolazine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013