A Study of Erythromycin and Rivaroxaban in Study Participants With Normal and Reduced Kidney Function - Full Text View

Purpose

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.

Condition	Intervention	Phase
Healthy Renal Insufficiency	Drug: Rivaroxaban (normal renal function) Drug: Rivaroxaban (mild and moderate renal impairment) Drug: Erythromycin (normal renal function) Drug: Erythromycin (mild and moderate renal function)	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

Drug Information available for: Erythromycin Erythromycin stearate Erythromycin ethylsuccinate Erythromycin phosphate Rivaroxaban

U.S. FDA Resources

Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:

Rivaroxaban plasma concentrations [ Time Frame: Up to Day 7 of Treatment Period 3 ] [ Designated as safety issue: No ]
Erythromycin plasma concentrations [ Time Frame: Up to Day 7 of Treatment Period 3 ] [ Designated as safety issue: No ]
Rivaroxaban urine concentrations [ Time Frame: Up to Day 7 of Treatment Period 3 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The number of patients with adverse events reported [ Time Frame: Up to 48 hours after Day 7 of Treatment Period 3 ] [ Designated as safety issue: No ]
Coagulation tests (prothrombin time [PT] and activated partial thromboplastin time [aPTT]) [ Time Frame: Up to Day 6 of Treatment Period 3 ] [ Designated as safety issue: No ]

Enrollment:	29
Study Start Date:	February 2011
Study Completion Date:	March 2012
Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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)	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: Erythromycin (normal renal function) One 500 mg tablet taken orally (by mouth) three times daily on Days 1 to 6 of Treatment Period 2
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)	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 (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
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)	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 (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

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.

Eligibility

Ages Eligible for Study:	35 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01309438

Locations

United States, Florida

Orlando, Florida, United States
United States, Minnesota

Minneapolis, Minnesota, United States

St. Paul, Minnesota, United States
United States, Tennessee

Knoxville, Tennessee, United States

Sponsors and Collaborators

Janssen Research & Development, LLC

Bayer HealthCare AG (BHC)

Investigators

Study Director:

Janssen Research & Development, LLC Clinical Trial

Janssen Research & Development, LLC

More Information

No publications provided

Responsible Party:	Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:	NCT01309438 History of Changes
Other Study ID Numbers:	CR017968, RIVAROXACS1001
Study First Received:	February 17, 2011
Last Updated:	January 4, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:

Healthy
Renal Insufficiency
Rivaroxaban (BAY 59-7939, JNJ-39039039)

Erythromycin
Pharmacokinetic
Pharmacodynamic

Additional relevant MeSH terms:

Renal Insufficiency
Kidney Diseases
Urologic Diseases
Erythromycin stearate
Erythromycin
Erythromycin Estolate
Erythromycin Ethylsuccinate
Gastrointestinal Agents

Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on May 23, 2013