A Study to Assess the Effects of 2 Different Prothrombin Complex Concentrates on the Pharmacodynamics of Rivaroxaban in Healthy Adult Volunteers

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Rivaroxaban 20 mg once daily; Drug: Beriplex P/N; Other: Saline; Drug: Profilnine SD; Drug: Rivaroxaban 20 mg twice daily

Study type: Interventional

Funder types: Industry

Identifiers

NCT01656330

2012-002313-20 (EudraCT Number)

RIVAROXNAP1003 (Other Identifier)

CR100867

Details and patient eligibility

About

The purpose of this study is to assess the use of 2 different Prothrombin Complex Concentrates (PCCs) on their ability to reverse (normalize) the pharmacodynamic effects of rivaroxaban in healthy adult volunteers.

Full description

This is a single-center, open-label (volunteers and staff will know the identity of all treatments), randomized (volunteers assigned to treatment by chance) study in healthy adult volunteers to assess the effects of 2 different Prothrombin Complex Concentrates (PCCs) (drugs that act to control bleeding) on the pharmacodynamics (ie, the study of the biochemical and physiological effects of a drug on the body) of rivaroxaban (a drug that acts to prevent the formation of blood clots). Eligible volunteers will receive treatment with rivaroxaban administered orally (by mouth) on Days 1-4. On Day 5, rivaroxaban will be administered orally before the randomized intravenous (IV) (into the vein) administration of 1 of 3 treatments: Profilnine SD (a 3-factor PCC), Beriplex P/N (a 4-factor PCC), or saline. Blood samples will be collected from healthy volunteers during the study to assess the activity of rivaroxaban. Safety will be monitored throughout the study. The total length of participation in the study for each volunteer will be approximately 28 days (includes a 21-day Screening Period and a 7-day Treatment Period).

Enrollment: 35 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Have coagulation test results of PT, INR and aPTT that are within normal limits
• Have a Body Mass Index (BMI; weight [kg]/height2 [m]2) between 18 and 30 kg/m2 (inclusive), and body weight between 50 and 100 kg
• Have blood pressure (after the volunteer is supine [lying down with the face up] for 5 minutes) between 90 and 140 mmHg systolic, inclusive, and between 50 and 90 mmHg diastolic
• Non-smoker

Exclusion criteria

• History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic (blood) disease, thrombosis, coagulation (blood clotting) disorders, lipid abnormalities, significant pulmonary (lung) disease, diabetes mellitus, renal (kidney) or hepatic (liver) insufficiency, thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the volunteer or that could interfere with the interpretation of the study results
• History of serious bleeding in the past, including gastrointestinal bleeding requiring hospitalization, intracranial (in the brain) bleeding of any type, or uncontrollable postoperative bleeding
• History of intracranial tumor or aneurysm or known abdominal aneurysm
• Known allergy to the study drug or any of the excipients of the formulation
• Known allergy to heparin or history of heparin-induced thrombocytopenia

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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35 participants in 3 patient groups

Rivaroxaban + Profilnine SD

Experimental group

Description:

Rivaroxaban 20 mg twice a day on Days 1-4 followed by rivaroxaban 20 mg once a day on Day 5 administered 4 hours before a single bolus dose of Profilnine SD 50 IU/kg.

Treatment:

Drug: Profilnine SD

Drug: Rivaroxaban 20 mg once daily

Drug: Rivaroxaban 20 mg twice daily

Rivaroxaban + Beriplex P/N

Experimental group

Description:

Rivaroxaban 20 mg twice a day on Days 1-4 followed by rivaroxaban 20 mg once a day on Day 5 administered 4 hours before a single bolus dose of Beriplex 50 IU/kg.

Treatment:

Drug: Beriplex P/N

Drug: Rivaroxaban 20 mg once daily

Drug: Rivaroxaban 20 mg twice daily

Rivaroxaban + Saline

Experimental group

Description:

Rivaroxaban 20 mg twice a day on Days 1-4 followed by rivaroxaban 20 mg once a day on Day 5 administered 4 hours before a single 100cc bolus of saline.

Treatment:

Drug: Rivaroxaban 20 mg once daily

Drug: Rivaroxaban 20 mg twice daily

Other: Saline