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

Registration Number
NCT01309438
Lead Sponsor
Janssen Research & Development, LLC
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
29
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Moderate renal impairmentRivaroxaban (mild and 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)
Mild renal impairmentErythromycin (mild and moderate 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 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)
Normal renal functionRivaroxaban (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)
Mild renal impairmentRivaroxaban (mild and 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)
Normal renal functionErythromycin (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)
Moderate renal impairmentErythromycin (mild and moderate 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 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)
Primary Outcome Measures
NameTimeMethod
Erythromycin plasma concentrationsUp to Day 7 of Treatment Period 3
Rivaroxaban urine concentrationsUp to Day 7 of Treatment Period 3
Rivaroxaban plasma concentrationsUp to Day 7 of Treatment Period 3
Secondary Outcome Measures
NameTimeMethod
The number of patients with adverse events reportedUp to 48 hours after Day 7 of Treatment Period 3
Coagulation tests (prothrombin time [PT] and activated partial thromboplastin time [aPTT])Up to Day 6 of Treatment Period 3
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