Clinical trial NCT01656330: A Study to Assess the Effects of 2 Different Prothrombin Complex Concentrates on the Pharmacodynamics of Rivaroxaban in Healthy Adult Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
Rivaroxaban
JNJ-39039039
BAY59-7939
Prothrombin Complex Concentrate (PCC)
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
Collaborators: name: Bayer
First posted: 2012-08-03
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief 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.

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 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

Primary outcomes:
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)
timeFrame: Days 1-6
Secondary outcomes:
measure: Rivaroxaban plasma concentrations
timeFrame: Days 1-6
measure: The number of healthy volunteers reporting adverse events
timeFrame: Days 1-6
measure: Changes from baseline in clinical laboratory tests performed
timeFrame: Day 1; Day 6
measure: Change from baseline in electrocardiogram (ECG) findings
timeFrame: Day 1; Day 6
measure: Change from baseline physical examination findings
timeFrame: Day 1; Day 6
measure: Change from baseline in vital signs measurements
timeFrame: Day 1; Day 6
Other outcomes:
Locations:
city: Merksem
country: Belgium
Study officials:
affiliation: Janssen Research & Development, L.L.C
name: Janssen Research & Development, L.L.C Clinical Trial
role: STUDY_DIRECTOR
References: