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

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01656330
• Other study ID #: CR100867
• Secondary ID: RIVAROXNAP100320
• Status: Completed
• Phase: Phase 1
• First received: July 31, 2012
• Last updated: January 23, 2017
• Start date: July 2012
• Est. completion date: August 2012

Study information

• Verified date: January 2017
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC	Bayer

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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.	Days 1-6
Secondary	Rivaroxaban plasma concentrations	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).	Days 1-6
Secondary	The number of healthy volunteers reporting adverse events	Adverse events reported are used to assess the safety and tolerability of study drugs.	Days 1-6
Secondary	Changes from baseline in clinical laboratory tests performed	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.	Day 1; Day 6
Secondary	Change from baseline in electrocardiogram (ECG) findings	Baseline for all ECG measurements will be defined as the last evaluation done before the first study drug administration.	Day 1; Day 6
Secondary	Change from baseline physical examination findings	Baseline for all physical examinations will be defined as the last evaluation done before the first study drug administration.	Day 1; Day 6
Secondary	Change from baseline in vital signs measurements	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.	Day 1; Day 6