A Pharmacokinetics, Pharmacodynamics and Safety Study of Single Dose of Rivaroxaban in Participants With End-Stage Renal Disease (ESRD) on Maintenance Hemodialysis

NCT02289703 | Completed Phase 1

• 2 other identifiers: CR105711RIVAROXCRF1001
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the pharmacokinetics (the study of the way a drug enters and leaves the blood and tissues over time) and pharmacodynamics (the way a drug may change body function) of a single 15-milligram (mg) dose of rivaroxaban in both healthy participants with a creatinine clearance (CLcr) greater than equal to (\>=) 80 milliliter per minute (mL/min) and clinically stable participants with end-stage renal disease (ESRD) on maintenance hemodialysis (a method used to remove waste material from the blood when the kidneys are unable to do so).

Conditions

End-Stage Renal Disease

Keywords

End-Stage Renal Disease; Healthy; Rivaroxaban; BAY 59-7939; JNJ-39039039; Xarelto; Hemodialysis; Blood Coagulation; Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• Maximum Observed Plasma Concentration (Cmax) of Rivaroxaban

  The Cmax is the maximum observed plasma concentration.

  Pre-dose up to 72 hrs post-dose

• Area Under the Plasma Concentration-time Curve From Time Zero to Last Quantifiable Time (AUClast) of Rivaroxaban

  The AUClast is the area under the plasma concentration-time curve from time zero to time of last quantifiable concentration.

  Pre-dose up to 72 hrs post-dose

• Area Under the Plasma Concentration-time Curve From Time Zero to Extrapolated Infinite Time (AUCinfinity) of Rivaroxaban

  The AUCinfinity is the area under the plasma concentration-time curve from time zero to extrapolated infinite time, calculated as the sum of AUClast and Clast/lambda(z), where AUClast is area under the plasma concentration-time curve from time zero to time of last quantifiable plasma concentration; Clast is the last observed quantifiable concentration; and lambda(z) is first-order rate constant associated with the terminal portion of the semilogarithmic drug concentration-time curve.

  Pre-dose up to 72 hrs post-dose

Secondary Outcomes (3)

• Maximum Observed Effect (Emax) for Prothrombin Time (PT), Factor Xa (FXa) Inhibition and Anti-FXa

  Pre-dose up to 72 hrs post-dose

• Area Under the Dose-Response Curve for Prothrombin Time (PT), Factor Xa (FXa) Inhibition and Anti-FXa

  Pre-dose up to 72 hrs post-dose

• Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)

  Screening up to end of study (Group A: maximum up to 43 days, Group B: maximum up to 25 days) or up to early withdrawal

Study Arms (2)

Group A

EXPERIMENTAL

Participants with end-stage renal disease (ESRD), will receive a single 15-milligram (mg) oral dose of rivaroxaban in Treatment Period 1 on Day 1, administered 2 hours before the start of a 4-hour hemodialysis session followed 7 to 14 days later by Treatment Period 2 wherein a single 15-mg oral dose of rivaroxaban will be given 3 hours after the completion of a 4-hour hemodialysis session on Day 1.

Drug: Rivaroxaban 15 mg

Group B

EXPERIMENTAL

Healthy control participants matching to 'Group A' participants, will receive a single 15-mg oral dose of rivaroxaban on Day 1.

Drug: Rivaroxaban 15 mg

Interventions

Rivaroxaban 15 mg DRUG

Single oral dose of rivaroxaban 15-mg tablet on Day 1 of each of the treatment periods.

Also known as: JNJ-39039039, BAY 59-7939, Xarelto

Group A; Group B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A. All Participants:
• \- Body mass index (BMI = weight in kilogram \[kg\] divided by the square of height in meter \[m\]) between 18 and 38 kg/m\^2, extremes included, and body weight not less than 50 kg
• Participants with end-stage renal disease (ESRD) requiring maintenance hemodialysis 2 or 3 times a week for at least 3 months prior to Screening
• Participants with clinically stable medical condition, consistent with ESRD, as judged by the investigator on the basis of the Screening physical examination, medical history, vital signs, 12-lead electrocardiogram (ECG), and results of clinical laboratory tests performed within 3 weeks of the first administration of study drug (unless judged to be clinically unimportant by the investigator or sponsor)
• Participants with diastolic blood pressure less than (\<) 110 millimeter of mercury (mmHg) and/or systolic blood pressure \<180 mmHg (at Screening only) recorded after 5 minutes rest in sitting position
• Healthy Participants on the basis of Screening physical examination, medical history, vital signs, 12-lead ECG, and results of clinical laboratory tests performed within 3 weeks prior to the administration of study drug
• Participants with diastolic blood pressure \<95 mmHg and/or systolic blood pressure \<150 mmHg recorded after 5 minutes rest in sitting position
• Participants with normal renal function characterized as having creatinine clearance (CLcr) \>80 mL/min by Cockcroft-Gault estimate

You may not qualify if:

• Participants with history of clinically significant medical illness prior to Screening including (but not limited to) chronic atrial fibrillation, hemodynamically significant valvular heart disease, heart failure (New York Heart Association Class \>=II) within 6 months prior to the Screening visit, cardiac revascularization within 6 months including percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery, ischemic stroke within 6 months, previous intracranial hemorrhage at any time, anemia with a hemoglobin concentration \<9 gram per deciliter (g/dL), or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results
• Participants diagnosed with current malignancy/active disease; (however, participants with clinically stable prostate cancer, basal cell carcinoma of the skin or who have not required antineoplastic treatment of previous cancers for at least one year are eligible)
• Participants with psychiatric disorders that would impair the participant's ability to participate or complete this study in the opinion of the investigator or the sponsor
• Participants with history of gastrointestinal disease (for example, Crohn's disease) which could result in impaired absorption of the study drugs
• Participants with any other disease or condition which could influence the physiological metabolic turnover of study drug (for example, endocrine diseases, febrile conditions, severe infections)
• Participants with history of significant hemorrhage and gastrointestinal ulceration within 6 months prior to the screening visit
• Participants with known primary coagulation disorders (for example, von Willebrand's disease, hemophilias)
• Participants with history of recurrent dialysis membrane thrombosis
• Participants with sensitivity to heparin
• Participants with dialysis for acute renal failure

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead
• Bayer: collaborator

Study Sites (1)

Unknown Facility

Knoxville, Tennessee, United States

Location

Related Links

• An Open-label Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety of a Single Dose of Rivaroxaban in Subjects with End-Stage Renal Disease (ESRD) on Maintenance Hemodialysis

MeSH Terms

Conditions

Kidney Failure, Chronic; Thrombosis

Interventions

Rivaroxaban

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; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2014
• First Posted: November 13, 2014
• Study Start: January 1, 2015
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: January 24, 2017

Record last verified: 2017-01

Locations

US (1)