Clinical trial NCT01435174: Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients
Official title: Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: End-stage Renal Disease
Cardiovascular Disease
Keywords: ranolazine
end-stage renal disease
pharmacokinetics
cardiovascular disease
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2011-09-16
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Pharmacokinetic Parameters of Ranolazine
timeFrame: At hours post-dose: 0, 2, 4, 8, 12, 15, 18, 20, 22, 23, 26, 30, 65
Secondary outcomes:
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Hospital
state: Michigan
Study officials:
affiliation: University of Michigan
name: Bruce A Mueller, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
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.