Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients

Cardiovascular Disease Clinical Trial

Official title:

Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01435174
• Other study ID #: IN-US-259-0123, HUM00051141
• Status: Completed
• Phase: Phase 4
• First received: September 14, 2011
• Last updated: September 13, 2017
• Start date: October 2011
• Est. completion date: March 2013

Study information

• Verified date: September 2017
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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)

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• End-stage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

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.
• QT Interval
Calculation of a QT interval will be performed throughout subject participation.

Locations

Country	Name	City	State
United States	University of Michigan Hospital	Ann Arbor	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan	Gilead Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic Parameters of Ranolazine	Peak Plasma Concentration (Cmax) with a 500 mg dose of ranolazine	At hours post-dose: 0, 2, 4, 8, 12, 15, 18, 20, 22, 23, 26, 30, 65