A Study to Assess the Independent Effects of 4-Factor Prothrombin Complex Concentrate and Tranexamic Acid on Bleeding/Pharmacodynamics in Healthy Participants

NCT02561923 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: CR10783239039039NAP1004
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the independent effects of both a 4-Factor prothrombin complex concentrate (PCC) - (Kcentra) and Tranexamic acid (TXA) on the bleeding parameters (bleeding duration and blood volume) following a punch biopsy, in addition to assessing their effects on the anticoagulant/pharmacodynamic (prothrombin time and endogenous thrombin potential) changes induced by rivaroxaban at steady state, to better understand their potential role in bleeding reversal.

Conditions

Healthy

Keywords

Healthy; Rivaroxaban; XARELTO

Outcome Measures

Primary Outcomes (9)

• Change From Baseline in Blood Volume in Part 1

  Volume of blood (BV) collected after a punch biopsy is performed.

  Day-1 (Baseline) and 4 hour (hr) postdose on Day 1

• Change From Baseline in Bleeding Duration in Part 1

  Bleeding duration (BD) after a punch biopsy is performed.

  Day-1 (Baseline) and 4 hr postdose on Day 1

• Mean Change in Thrombin Generation Assay (TGA) - Endogenous Thrombin Potential (ETP) Lag-time in Part 2

  The thrombin generation assay (TGA) is based on the premise that measurements of thrombin generation are indicative of the overall coagulating capacity of the individual. The data derived from the thrombography can be used to determine the ETP, which in turn provides a functional assessment of the overall clotting cascade. Change in lag time (time required until thrombin is generated) will be observed.

  Predose (Baseline) and up to 72 hrs postdose on Day 4

• Mean Change in Thrombin Generation Assay (TGA) - Endogenous Thrombin Potential (ETP) Peak in Part 2

  The thrombin generation assay (TGA) is based on the premise that measurements of thrombin generation are indicative of the overall coagulating capacity of the individual. The data derived from the thrombography can be used to determine the ETP, which in turn provides a functional assessment of the overall clotting cascade. Change in peak (the maximal effect on thrombin generation) will be observed.

  Predose (Baseline) and 72 hours postdose on Day 4

• Mean Change in Thrombin Generation Assay (TGA) - Endogenous Thrombin Potential (ETP) Time to Peak in Part 2

  The thrombin generation assay (TGA) is based on the premise that measurements of thrombin generation are indicative of the overall coagulating capacity of the individual. The data derived from the thrombography can be used to determine the ETP, which in turn provides a functional assessment of the overall clotting cascade. Change in time-to-peak (time required to reach maximal effect on thrombin generation) will be observed.

  Predose (Baseline) and 72 hours postdose on Day 4

• Mean Change in Thrombin Generation Assay (TGA) - Endogenous Thrombin Potential (ETP) Area Under Curve (AUC) in Part 2

  The thrombin generation assay (TGA) is based on the premise that measurements of thrombin generation are indicative of the overall coagulating capacity of the individual. The data derived from the thrombography can be used to determine the ETP, which in turn provides a functional assessment of the overall clotting cascade. Change in AUC (the overall effect on thrombin generation) will be observed.

  Predose (Baseline) up to 72 hours on Day 4

• Mean Change in Prothrombin Time (PT) in Part 2

  Prothrombin Time is a global clotting test that is used for the assessment of the extrinsic pathway of the blood coagulation cascade.

  Predose (Baseline) up to 72 hours on Day 4

• Change From Baseline in Blood Volume in Part 2

  Predose (Baseline) and 72 hours on Day 4

• Change From Baseline in Bleeding Duration in Part 2

  Predose (Baseline) and 72 hours on Day 4

Secondary Outcomes (14)

• Maximum Observed Plasma Concentration (Cmax) in Part 1

  Predose and up to 24 hrs postdose on Day 1

• Time to Maximum Observed Plasma Concentration in Part 1 (Tmax)

  Predose and up to 24 hrs post-dose

• Area under Plasma Concentration Time Curve From Time 0 to 24 in Part 1 (AUC [0 TO 24]

  Predose and up to 24 hrs postdose on Day 1

• Maximum Observed Plasma Concentration (Cmax) in Part 2

  Predose and up to 72 hrs postdose on Day 4

• Minimum Observed Plasma Concentration (Cmin) in Part 2

  Predose Days 1 to 4

Study Arms (4)

Rivaroxaban

EXPERIMENTAL

Participants will be administered a single 20 milligram (mg) dose of rivaroxaban orally on Day 1 in Part 1.

Drug: Rivaroxaban

Rivaroxaban plus tranexamic acid (TXA)

EXPERIMENTAL

Participants will be administered rivaroxaban (20 mg every 12 hrs) on Days 1 through 3 and a single 20 mg dose will be given on the morning of Day 4, all doses given orally. Following rivaroxaban adminsitration on Day 4, tranexamic acid (TXA) 1.0 gram (g) - (over 10 mins) intravenously administered on Day 4 in Part 2.

Drug: Rivaroxaban; Drug: Tranexamic acid

Rivaroxaban plus Kcentra

EXPERIMENTAL

Participants will be administered rivaroxaban (20 mg every 12 hrs) on Days 1 through 3 and a single 20 mg dose will be given on the morning of Day 4, all doses given orally. Following rivaroxaban adminsitration on Day 4, participants will be randomized to receive a single dose of Kcentra (a 4-factor PCC), 50 international units per kilogram (IU/kg), intravenously administered (maximum rate of 210 \[international units per minute\] IU/min) on Day 4 in Part 2.

Drug: Rivaroxaban; Drug: Kcentra, a 4-factor PCC

Rivaroxaban plus Saline

EXPERIMENTAL

Participants will be administered rivaroxaban (20 mg every 12 hrs) on Days 1 through 3 and a single 20 mg dose will be given on the morning of Day 4, all doses given orally. Following rivaroxaban adminsitration on Day 4, saline \[Kcentra saline control or TXA saline control\] on Day 4 in Part 2.

Drug: Rivaroxaban; Drug: Saline

Interventions

Rivaroxaban DRUG

A single dose of 20 milligram (mg) of rivaroxaban orally will be administered to participants on Day 1 in part 1 and through day 1 and 3 with a final 20 mg dose administered on the morning of Day 4 in part 2.

Rivaroxaban; Rivaroxaban plus Kcentra; Rivaroxaban plus Saline; Rivaroxaban plus tranexamic acid (TXA)

Tranexamic acid DRUG

1.0 g single dose of tranexamic acid (TXA), intravenously administered (over 10 mins) on Day 4.

Rivaroxaban plus tranexamic acid (TXA)

Kcentra, a 4-factor PCC DRUG

Kcentra, a 4-factor PCC, 50 IU/kg, single dose, intravenously administered (maximum rate of 210 \[international units\] IU/min) on Day 4.

Rivaroxaban plus Kcentra

Saline DRUG

Saline \[Kcentra saline control or TXA saline control\] on Day 4.

Rivaroxaban plus Saline

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Body mass index (weight kilogram \[kg\]/height\^2 meters \[m\]\^2) between 18 and 30 kg/m2 (inclusive), and body weight between 50 and 100 kg;
• Participants must have coagulation test results of prothrombin time (PT) and a partial thromboplastin time (PTT) within normal limits at Screening
• Must have normal renal function, as per medical history
• If a woman, must be postmenopausal (no spontaneous menses for at least 2 years), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control (eg, double-barrier method or male partner sterilization) before entry and throughout the study. (Note: combined hormonal contraception should not be used)
• Non-smoker (Note: subjects should not have used nicotine-containing products within 30 days before study drug administration)
• If a woman, must have a negative serum Beta-human chorionic gonadotropin (hCG)\] pregnancy test at Screening; and a negative serum pregnancy test on Day -1 of the study
• If a man, must agree to use adequate contraception method as deemed appropriate by the investigator (eg, vasectomy, double-barrier, partner using effective contraception) and to not donate sperm during the study and for 3 months after receiving the last dose of study drug

You may not qualify if:

• History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease (including history of definite myocardial infarction, cerebrovascular accident, percutaneous transluminal coronary angioplasty or coronary artery bypass graft within 6 months before the Screening visit, or a previous intracranial hemorrhage at any time, known history of lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, neurologic or psychiatric disease, seizure disorder, infection, skin disease, or any other illness that the investigator considers should exclude the subject or that could interfere with the interpretation of the study results
• Participants with any history of thrombosis, inherited or acquired thrombophilia, bleeding diathesis or coagulopathy (including any abnormal bleeding or blood dyscrasias), hematologic disease, clinically significant hemorrhagic disorder, excessive bruising, bleeding from nose or gums or known disorders with increased bleeding risk (eg, acute gastritis, acute peptic ulcer), serious bleeding including gastrointestinal bleeding requiring hospitalization, intracranial bleeding of any type, or uncontrollable postoperative bleeding
• Known antithrombin III, Protein C, or Protein S deficiency, Factor V Leiden or prothrombin gene 20210 mutation, anticardiolipin (immunoglobulin G \[IgG\] and immunoglobulin M \[IgM\]) or antiphospholipid antibodies, or family history of unexplained thrombotic disorders
• History of intracranial tumor or aneurysm or known abdominal aneurysm
• Clinically significant abnormal physical examination, vital signs or 12-lead electrocardigram \[ECG\] at Screening or at admission to the study center on Day -1, as deemed appropriate by the investigator. This would include: resting pulse \>100 or \<40 beats per min, blood pressure systolic \>140 or \<90 millimeters per mercuric level \[mmHg\], and diastolic blood pressure \> 90 or \< 50 mmHg (pulse and blood pressure measurements should be taken in a supine position, after resting for at least 5 minutes)
• Participants for whom surface blood vessels could not be visualized, or who have a history of likelihood of forming keloid scars
• Use of any prescription or nonprescription medication (including antiplatelet, anticoagulants, aspirin, non-steroidal anti-inflammatory drugs, vitamins and herbal supplements), within 7 days before the first dose of the study drug is scheduled
• Known allergy to the study drugs or any of the excipients of the formulations
• Unable to swallow solid, oral dosage forms whole with the aid of water (participants may not chew, divide, dissolve, or crush the study drug)

Sponsors & Collaborators

• Janssen Scientific Affairs, LLC: lead
• Bayer: collaborator

Study Sites (1)

Unknown Facility

Overland Park, Kansas, United States

Location

Related Links

• Randomized,Parallel-Group,2-Part Study to Assess the Independent Effects of 4-Factor Prothrombin Complex Concentrate and Tranexamic Acid on Bleeding Parameters and Pharmacodynamics After Punch Biopsy Procedure in Healthy Subjects Treated With Rivaroxaban

MeSH Terms

Interventions

Rivaroxaban; Tranexamic Acid; Sodium Chloride

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Janssen Scientific Affairs, LLC Clinical Trial

  Janssen Scientific Affairs, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2015
• First Posted: September 28, 2015
• Study Start: August 27, 2015
• Primary Completion: June 17, 2016
• Study Completion: June 17, 2016
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

US (1)