Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients

• Sponsor: University of Michigan (Other)
• Overall Status: Completed
• CT.gov ID: NCT01435174
• Collaborator: Gilead Sciences (Industry)
• Enrollment: 17
• Location: 1
• Arm: 1
• Duration (Months): 17
• Patients Per Site Per Month: 1

Study Details

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.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

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 Names: 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

Outcome Measures

Primary Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 74 Years
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bruce A. Mueller, Associate Dean of Academic Affairs, University of Michigan
• ClinicalTrials.gov Identifier: NCT01435174
• Other Study ID Numbers: IN-US-259-0123, HUM00051141
• First Posted: Sep 16, 2011
• Last Update Posted: Oct 16, 2017
• Last Verified: Sep 1, 2017

• Keywords provided by Bruce A. Mueller, Associate Dean of Academic Affairs, University of Michigan: ranolazine; end-stage renal disease; pharmacokinetics; cardiovascular disease
• Additional relevant MeSH terms: Kidney Diseases; Kidney Failure, Chronic; Cardiovascular Diseases; Ranolazine; Dialysis Solutions

Study Results

Participant Flow

Arm/Group Title	Ranolazine
Arm/Group Description	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.
Period Title: Overall Study
STARTED	17
COMPLETED	8
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	Ranolazine
Arm/Group Description	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.
Overall Participants	17
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	33
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	17 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	8 47.1%
Male	9 52.9%
Region of Enrollment (participants) [Number]
United States	17 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranolazine
Arm/Group Description	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.
Measure Participants	8
Mean (Standard Deviation) [mcg/mL]	0.65 (0.27)

Adverse Events

Arm/Group Title	Ranolazine
Arm/Group Description	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.
All Cause Mortality
	Ranolazine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ranolazine
	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)
Cardiac disorders
Elevated Potassium with EKG Changes	1/8 (12.5%)
Other (Not Including Serious) Adverse Events
	Ranolazine
	Affected / at Risk (%)	# Events
Total	0/8 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.