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

July 31, 2012
February 18, 2013
July 2012
August 2012   (final data collection date for primary outcome measure)
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.
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 ]
Pharmacodynamic (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.
Complete list of historical versions of study NCT01656330 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
A Study to Assess the Effects of 2 Different Prothrombin Complex Concentrates on the Pharmacodynamics of Rivaroxaban in Healthy Adult Volunteers
Randomized, Parallel-Group, Open-Label Study to Assess the Effects of 3-Factor and 4-Factor Prothrombin Complex Concentrates on the Pharmacodynamics of Rivaroxaban

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.

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).

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Healthy
  • 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.
  • 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
  • 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.
  • 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.
    Interventions:
    • Drug: Rivaroxaban 20 mg twice daily
    • Drug: Rivaroxaban 20 mg once daily
    • Drug: Profilnine SD
  • 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.
    Interventions:
    • Drug: Rivaroxaban 20 mg twice daily
    • Drug: Rivaroxaban 20 mg once daily
    • Drug: Beriplex P/N
  • 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.
    Interventions:
    • Drug: Rivaroxaban 20 mg twice daily
    • Drug: Rivaroxaban 20 mg once daily
    • Other: Saline
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
35
August 2012
August 2012   (final data collection date for primary outcome measure)

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
Both
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Belgium
 
NCT01656330
CR100867, RIVAROXNAP1003, 2012-002313-20
Not Provided
Janssen Research & Development, LLC
Janssen Research & Development, LLC
Not Provided
Study Director: Janssen Research & Development, L.L.C Clinical Trial Janssen Research & Development, L.L.C
Janssen Research & Development, LLC
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP