Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients

NCT01435174 | Completed Phase 4 Results

• 1 other identifier: IN-US-259-0123, HUM00051141
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

End-stage Renal Disease; Cardiovascular Disease

Keywords

ranolazine; end-stage renal disease; pharmacokinetics; cardiovascular disease

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Ranolazine

EXPERIMENTAL

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

Drug: Ranolazine; Procedure: Pharmacokinetic Blood and Dialysate Sampling; Procedure: QT Interval

Interventions

Ranolazine DRUG

A single dose of two oral ranolazine extended release 500 mg tablets

Also known as: Ranexa

Ranolazine

Pharmacokinetic Blood and Dialysate Sampling PROCEDURE

Blood samples collected to assess ranolazine plasma and dialysate concentrations.

Also known as: Ranexa, PK sampling

Ranolazine

QT Interval PROCEDURE

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

Also known as: Ranexa, QT interval calculation

Ranolazine

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Michigan: lead
• Gilead Sciences: collaborator

Study Sites (1)

University of Michigan Hospital

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• 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.

  PMID: 30909832 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic; Cardiovascular Diseases

Interventions

Ranolazine

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Bruce A. Mueller
• Organization: University of Michigan College of Pharmacy

muellerb@umich.edu

7346154578

Study Officials

• Bruce A Mueller, PharmD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Dean of Academic Affairs

Study Record Dates

• First Submitted: September 14, 2011
• First Posted: September 16, 2011
• Study Start: October 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: October 16, 2017
• Results First Posted: June 25, 2014

Record last verified: 2017-09

Locations

US (1)