Cardiovascular Disease, End-stage Renal Disease
Conditions
Keywords
ranolazine, end-stage renal disease, pharmacokinetics, cardiovascular disease
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.
Interventions
DRUGRanolazine
A single dose of two oral ranolazine extended release 500 mg tablets
Blood samples collected to assess ranolazine plasma and dialysate concentrations.
PROCEDUREQT Interval
Calculation of a QT interval will be performed throughout subject participation.
Sponsors
Gilead Sciences
University of Michigan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameters of Ranolazine | At hours post-dose: 0, 2, 4, 8, 12, 15, 18, 20, 22, 23, 26, 30, 65 | Peak Plasma Concentration (Cmax) with a 500 mg dose of ranolazine |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ranolazine End-stage renal disease patients receiving a single-dose of ranolazine and a concomitant hemodialysis session.
Ranolazine: A single dose of two oral ranolazine extended release 500 mg tablets
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. | 17 |
| Total | 17 |
Baseline characteristics
| Characteristic | Ranolazine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Age, Continuous | 33 years |
| Region of Enrollment United States | 17 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 8 |
| serious Total, serious adverse events | 1 / 8 |
Outcome results
Primary
Pharmacokinetic Parameters of Ranolazine
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranolazine | Pharmacokinetic Parameters of Ranolazine | 0.65 mcg/mL | Standard Deviation 0.27 |