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Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients

Primary Purpose

End-stage Renal Disease, Cardiovascular Disease

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Ranolazine
Pharmacokinetic Blood and Dialysate Sampling
QT Interval
Sponsored by
University of Michigan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for End-stage Renal Disease focused on measuring ranolazine, end-stage renal disease, pharmacokinetics, cardiovascular disease

Eligibility Criteria

18 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

  • University of Michigan Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ranolazine

Arm Description

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

Outcomes

Primary Outcome Measures

Pharmacokinetic Parameters of Ranolazine
Peak Plasma Concentration (Cmax) with a 500 mg dose of ranolazine

Secondary Outcome Measures

Full Information

First Posted
September 14, 2011
Last Updated
September 13, 2017
Sponsor
University of Michigan
Collaborators
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT01435174
Brief Title
Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients
Official Title
Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
October 2011 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Michigan
Collaborators
Gilead Sciences

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End-stage Renal Disease, Cardiovascular Disease
Keywords
ranolazine, end-stage renal disease, pharmacokinetics, cardiovascular disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ranolazine
Arm Type
Experimental
Arm Description
End-stage renal disease patients receiving a single-dose of ranolazine and a concomitant hemodialysis session.
Intervention Type
Drug
Intervention Name(s)
Ranolazine
Other Intervention Name(s)
Ranexa
Intervention Description
A single dose of two oral ranolazine extended release 500 mg tablets
Intervention Type
Procedure
Intervention Name(s)
Pharmacokinetic Blood and Dialysate Sampling
Other Intervention Name(s)
Ranexa, PK sampling
Intervention Description
Blood samples collected to assess ranolazine plasma and dialysate concentrations.
Intervention Type
Procedure
Intervention Name(s)
QT Interval
Other Intervention Name(s)
Ranexa, QT interval calculation
Intervention Description
Calculation of a QT interval will be performed throughout subject participation.
Primary Outcome Measure Information:
Title
Pharmacokinetic Parameters of Ranolazine
Description
Peak Plasma Concentration (Cmax) with a 500 mg dose of ranolazine
Time Frame
At hours post-dose: 0, 2, 4, 8, 12, 15, 18, 20, 22, 23, 26, 30, 65

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruce A Mueller, PharmD
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
30909832
Citation
Scoville BA, Segal JH, Salama NN, Heung M, Bleske BE, Eyler RF, Mueller BA. Single dose oral ranolazine pharmacokinetics in patients receiving maintenance hemodialysis. Ren Fail. 2019 Nov;41(1):118-125. doi: 10.1080/0886022X.2019.1585371.
Results Reference
derived

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Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients

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