A Study of Erythromycin and Rivaroxaban in Study Participants With Normal and Reduced Kidney Function

Overview

The purpose of this study is to evaluate the pharmacokinetics and pharmacodynamics of rivaroxaban when administered with erythromycin to study participants with mild or moderate renal impairment compared to the pharmacokinetics and pharmacodynamics of rivaroxaban administered to study participants with normal renal function.

Full Title of Study: “An Open-Label Study to Estimate the Effect of Multiple Doses of Erythromycin on the Pharmacokinetics, Pharmacodynamics and Safety of a Single Dose of Rivaroxaban in Subjects With Renal Impairment and Normal Renal Function”

Study Type

  • Study Type: Interventional
  • Study Design
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: March 2012

Detailed Description

This is an open-label study (participants and the study physician [Investigator] will know the identity of the assigned treatments) to compare the pharmacokinetics (PK) (how the drugs are absorbed in the body) and pharmacodynamics (PD) (the actions or effects of drugs on the body) of rivaroxaban in study participants with mild or moderate renal impairment (reduced kidney function) receiving multiple doses of erythromycin, to the PK and PD of a single dose of rivaroxaban administered alone in study participants with normal renal function. The study drugs used will be rivaroxaban, a drug that acts to thin the blood to prevent the formation of blood clots, and erythromycin, an antibiotic used to treat patients with bacterial infections. Study participants with normal renal function will receive Treatment A (1 oral [by mouth] dose 10 mg rivaroxaban for 1 day) and Treatment C (500 mg oral erythromycin 3x a day (t.i.d.) on Days 1-6 + 1 oral dose of 10 mg rivaroxaban on Day 5). Study participants with mild and moderate renal impairment will receive Treatment A, Treatment B (500 mg oral erythromycin t.i.d. on Days 1-6 + 1 oral dose of 5 mg rivaroxaban Day 5), and Treatment C. Treatments A, B, and C will be separated by up to 14 days.

Interventions

  • Drug: Rivaroxaban (normal renal function)
    • One 10 mg tablet of rivaroxaban taken orally (by mouth) on Day 1 of Treatment Period 1; One 10 mg tablet of rivaroxaban taken orally on Day 5 of Treatment Period 2
  • Drug: Rivaroxaban (mild and moderate renal impairment)
    • One 10 mg tablet of rivaroxaban taken orally (by mouth) on Day 1 of Treatment Period 1; One 5 mg tablet of rivaroxaban taken orally on Day 5 of Treatment Period 2; One 10 mg tablet of rivaroxaban taken orally on Day 5 of Treatment Period 3
  • Drug: Erythromycin (normal renal function)
    • One 500 mg tablet taken orally (by mouth) three times daily on Days 1 to 6 of Treatment Period 2
  • Drug: Erythromycin (mild and moderate renal function)
    • One 500 mg tablet taken orally (by mouth) three times daily on Days 1 to 6 of Treatment Periods 2 and 3

Arms, Groups and Cohorts

  • Experimental: Normal renal function
    • Treatment Period 1 (1 dose of 10 mg rivaroxaban on Day 1) followed, up to 14 days later, by Treatment Period 2 (500 mg erythromycin three times daily on Days 1 to 6 plus 1 dose of 10 mg rivaroxaban on Day 5)
  • Experimental: Mild renal impairment
    • Treatment Period 1 (1 dose of 10 mg rivaroxaban on Day 1) followed, up to 14 days later, by Treatment Period 2 (500 mg erythromycin three times daily on Days 1 to 6 plus 1 dose of 5 mg rivaroxaban on Day 5) followed, up to 14 days later, by Treatment Period 3 (500 mg erythromycin three times daily on Days 1 to 6 plus 1 dose of 10 mg rivaroxaban on Day 5)
  • Experimental: Moderate renal impairment
    • Treatment Period 1 (1 dose of 10 mg rivaroxaban on Day 1) followed, up to 14 days later, by Treatment Period 2 (500 mg erythromycin three times daily on Days 1 to 6 plus 1 dose of 5 mg rivaroxaban on Day 5) followed, up to 14 days later, by Treatment Period 3 (500 mg erythromycin three times daily on Days 1 to 6 plus 1 dose of 10 mg rivaroxaban on Day 5)

Clinical Trial Outcome Measures

Primary Measures

  • Rivaroxaban plasma concentrations
    • Time Frame: Up to Day 7 of Treatment Period 3
  • Erythromycin plasma concentrations
    • Time Frame: Up to Day 7 of Treatment Period 3
  • Rivaroxaban urine concentrations
    • Time Frame: Up to Day 7 of Treatment Period 3

Secondary Measures

  • The number of patients with adverse events reported
    • Time Frame: Up to 48 hours after Day 7 of Treatment Period 3
  • Coagulation tests (prothrombin time [PT] and activated partial thromboplastin time [aPTT])
    • Time Frame: Up to Day 6 of Treatment Period 3

Participating in This Clinical Trial

Inclusion Criteria

  • Have a body mass index (BMI) between 18 and 38 kg/m2, inclusive – Have a body weight of not less than 50 kg and have been characterized as having normal renal function (creatinine clearance [CLCR] > 80 mL/min), mild renal impairment (CLCR 50-79 mL/min) or moderate renal impairment (CLCR 30-49 mL/min) – Study participants with renal impairment should have stable renal disease as determined by the Investigator Exclusion Criteria:

  • History of current clinically significant medical illness or any other illness that the Investigator considers should exclude the study participant or that could interfere with the interpretation of the study results – Additional exclusion criteria for study participants with normal renal function include: diastolic blood pressure > 95 mm Hg and/or systolic blood pressure > 150 mm Hg) – Additional exclusion criteria for study participants with renal impairment include: diastolic blood pressure > 100 mm Hg and/or systolic blood pressure > 170 mm Hg, other routine laboratory parameters > upper limit of normal which could not be explained by the underlying renal disease unless judged to be clinically unimportant by the investigator, have acute renal failure, or be a recipient of transplanted organs – Have severe renal impairment (CLCR < 30 mL/min)

Gender Eligibility: All

Minimum Age: 35 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Janssen Research & Development, LLC
  • Collaborator
    • Bayer
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Janssen Research & Development, LLC Clinical Trial, Study Director, Janssen Research & Development, LLC

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.