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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01656330
First received: July 31, 2012
Last updated: February 18, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: Rivaroxaban 20 mg twice daily
Drug: Rivaroxaban 20 mg once daily
Drug: Profilnine SD
Drug: Beriplex P/N
Other: Saline
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Randomized, Parallel-Group, Open-Label Study to Assess the Effects of 3-Factor and 4-Factor Prothrombin Complex Concentrates on the Pharmacodynamics of Rivaroxaban

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Measurement of pharmacodynamic (PD) variables: prothrombin time (PT), International Normalized Ratio (INR), activated partial thromboplastin time (aPTT), thrombin generation assay (TGA) and anti-Factor Xa (anti-FXa) [ Time Frame: Days 1-6 ] [ Designated as safety issue: No ]
    Pharamacodymic (PD) variables (ie, PT, INR, aPTT, TGA, and anti-FXa) are blood coagulation (or clotting) tests. These blood clotting tests will be performed to assess the effects of Prothrombin Complex Concentrates (PCCs) (Profilnine SD or Beriplex P/N) on the pharmacodynamics of rivaroxaban.


Secondary Outcome Measures:
  • Rivaroxaban plasma concentrations [ Time Frame: Days 1-6 ] [ Designated as safety issue: No ]
    Rivaroxaban plasma concentrations will be measured to assess the pharmacokinetics (the study of the extent and rate of absorption, distribution, metabolism, and excretion of a drug in the body [ie, the study of what the body does to the drug]) of rivaroxaban at steady state (steady state is the time when the rate of absorption of the drug into the body equals the rate of elimination from the body).

  • The number of healthy volunteers reporting adverse events [ Time Frame: Days 1-6 ] [ Designated as safety issue: No ]
    Adverse events reported are used to assess the safety and tolerability of study drugs.

  • Changes from baseline in clinical laboratory tests performed [ Time Frame: Day 1; Day 6 ] [ Designated as safety issue: No ]
    Clinical laboratory tests include chemistry, hematology, urinalysis, and coagulation. Baseline for all laboratory evaluations will be defined as the last evaluation done before the first study drug administration.

  • Change from baseline in electrocardiogram (ECG) findings [ Time Frame: Day 1; Day 6 ] [ Designated as safety issue: No ]
    Baseline for all ECG measurements will be defined as the last evaluation done before the first study drug administration.

  • Change from baseline physical examination findings [ Time Frame: Day 1; Day 6 ] [ Designated as safety issue: No ]
    Baseline for all physical examinations will be defined as the last evaluation done before the first study drug administration.

  • Change from baseline in vital signs measurements [ Time Frame: Day 1; Day 6 ] [ Designated as safety issue: No ]
    Vital signs measurements include pulse/heart rate and blood pressure (systolic and diastolic). Baseline vital signs measurements will be defined as the last evaluation done before the first study drug administration.


Enrollment: 35
Study Start Date: July 2012
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rivaroxaban + Profilnine SD
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.
Drug: Rivaroxaban 20 mg twice daily
One rivaroxaban 20 mg tablet administered twice a day (b.i.d.) for 4 days (Days 1-4). Interpretation by CTRL: Concentration type = Exact; Number = 20; unit=mg; route: oral use for 4 days.
Drug: Rivaroxaban 20 mg once daily
One rivaroxaban 20 mg tablet administered once daily on Day 5. Interpretation by CTRL: Concentration type = Exact; Number = 20; unit=mg; route: oral use for 1 day.
Drug: Profilnine SD
Single bolus dose of Profilnine SD 50 IU/kg administered by intravenous (IV) injection on Day 5. Interpretation by CTRL: Concentration type = Exact; Number = 50; unit=IU/kg; route: intraveous use.
Experimental: Rivaroxaban + Beriplex P/N
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.
Drug: Rivaroxaban 20 mg twice daily
One rivaroxaban 20 mg tablet administered twice a day (b.i.d.) for 4 days (Days 1-4). Interpretation by CTRL: Concentration type = Exact; Number = 20; unit=mg; route: oral use for 4 days.
Drug: Rivaroxaban 20 mg once daily
One rivaroxaban 20 mg tablet administered once daily on Day 5. Interpretation by CTRL: Concentration type = Exact; Number = 20; unit=mg; route: oral use for 1 day.
Drug: Beriplex P/N
Single bolus dose of Beriplex P/N 50 IU/kg administered by intravenous (IV) injection on Day 5 Interpretation by CTRL: Concentration type = Exact ; Number = 50; unit=IU/kg; route : intravenous use
Experimental: Rivaroxaban + Saline
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.
Drug: Rivaroxaban 20 mg twice daily
One rivaroxaban 20 mg tablet administered twice a day (b.i.d.) for 4 days (Days 1-4). Interpretation by CTRL: Concentration type = Exact; Number = 20; unit=mg; route: oral use for 4 days.
Drug: Rivaroxaban 20 mg once daily
One rivaroxaban 20 mg tablet administered once daily on Day 5. Interpretation by CTRL: Concentration type = Exact; Number = 20; unit=mg; route: oral use for 1 day.
Other: Saline
Single 100 cc bolus of saline administered by intravenous (IV) injection on Day 5. Interpretation by CTRL: Concentration type = Exact ; Number = 100; unit=cc; route : intravenous use use.

Detailed 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).

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01656330

Locations
Belgium
Merksem, Belgium
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, L.L.C Clinical Trial Janssen Research & Development, L.L.C
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01656330     History of Changes
Other Study ID Numbers: CR100867, RIVAROXNAP1003, 2012-002313-20
Study First Received: July 31, 2012
Last Updated: February 18, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Janssen Research & Development, LLC:
Healthy
Rivaroxaban
JNJ-39039039
BAY59-7939
Prothrombin Complex Concentrate (PCC)

Additional relevant MeSH terms:
Rivaroxaban
Thrombin
Anticoagulants
Coagulants
Hematologic Agents
Hemostatics
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014