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HealthyPhase 1NCT02561923

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

A Phase 1 study testing Rivaroxaban, Tranexamic acid and Kcentra, a 4-factor PCC in people with Healthy, run by Janssen Scientific Affairs, LLC at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Healthy
What is being tested?
Rivaroxaban, Tranexamic acid and Kcentra, a 4-factor PCC
Could I receive a placebo?
No, everyone receives an active treatment
How many people
158 participants
Where
1 siteUnited States
Study dates
27 Aug 2015to 17 Jun 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Study site

    Overland Park, Kansas

Other trials in United States

About this study

Official title: 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 a Punch Biopsy Procedure in Healthy Subjects Treated With Rivaroxaban

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.

Read the detailed description

This is a 2 part, single center study to be conducted in healthy men and women. Part 1 (open-label) consists of Screening Phase (within 28 days before admission into the study center on Day -1), followed by a 3 day treatment period and a follow-up visit on Day 8. A single oral 20 milligram (mg) dose of rivaroxaban will be administered on Day 1. Pharmacokinetic (PK), pharmacodynamics (PD), and punch biopsy parameters will be assessed. Part 2 (double-blind) consists of Screening Phase (within 28 days before admission into the study center on Day -1), followed by a 8 day treatment period (Day -1 to Day 7) and a follow-up visit on Day 11. Rivaroxaban (20 mg every 12 hrs) will be administered on Days 1 through 3 and single 20 mg dose will be given on the morning of Day 4. A single dose of either 4-factor PCC, TXA or saline (Placebo) will be administered in a randomized, blinded fashion on Day 4. PK, PD, Exploratory Bio-markers and punch biopsy parameters will be assessed. Participants' safety will be monitored throughout the study.

Conditions
Healthy
Being tested
Rivaroxaban, Tranexamic acid, Kcentra, a 4-factor PCC, Saline
Keywords
Healthy, Rivaroxaban, XARELTO

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RivaroxabanDrug

    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.

  • Tranexamic acidDrug

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

  • Kcentra, a 4-factor PCCDrug

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

  • SalineDrug

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

Study groups in NCT02561923
Study groupRoleWhat they receive
RivaroxabanExperimentalParticipants will be administered a single 20 milligram (mg) dose of rivaroxaban orally on Day 1 in Part 1.
Receives: Drug: Rivaroxaban
Rivaroxaban plus tranexamic acid (TXA)ExperimentalParticipants 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.
Receives: Drug: Rivaroxaban; Drug: Tranexamic acid
Rivaroxaban plus KcentraExperimentalParticipants 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.
Receives: Drug: Rivaroxaban; Drug: Kcentra, a 4-factor PCC
Rivaroxaban plus SalineExperimentalParticipants 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.
Receives: Drug: Rivaroxaban; Drug: Saline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in Blood Volume in Part 1

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

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

  2. Change From Baseline in Bleeding Duration in Part 1

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

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

  3. 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.

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

  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.

    Measured: Predose (Baseline) and 72 hours postdose on Day 4

  5. 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.

    Measured: Predose (Baseline) and 72 hours postdose on Day 4

  6. 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.

    Measured: Predose (Baseline) up to 72 hours on Day 4

  7. 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.

    Measured: Predose (Baseline) up to 72 hours on Day 4

  8. Change From Baseline in Blood Volume in Part 2

    Measured: Predose (Baseline) and 72 hours on Day 4

  9. Change From Baseline in Bleeding Duration in Part 2

    Measured: Predose (Baseline) and 72 hours on Day 4

Secondary outcomes (14)
  1. Maximum Observed Plasma Concentration (Cmax) in Part 1

    Measured: Predose and up to 24 hrs postdose on Day 1

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

    Measured: Predose and up to 24 hrs post-dose

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

    Measured: Predose and up to 24 hrs postdose on Day 1

  4. Maximum Observed Plasma Concentration (Cmax) in Part 2

    Measured: Predose and up to 72 hrs postdose on Day 4

  5. Minimum Observed Plasma Concentration (Cmin) in Part 2

    Measured: Predose Days 1 to 4

  6. Time to Maximum Observed Plasma Concentration (Tmax) in Part 2

    Measured: Predose and up to 72 hrs postdose on Day 4

  7. Area under plasma concentration time curve during the dosing interval (AUCtau) in Part 2

    Measured: Predose and up to 24 hours

  8. Mean Change in Thrombin Generation Assay (TGA) Endogenous Thrombin Potential (ETP) Lag-time in Part 1

    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.

    Measured: Predose (Baseline) up to 24 hours on Day 1

  9. Mean Change in Thrombin Generation Assay (TGA) Endogenous Thrombin Potential (ETP) Peak in Part 1

    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.

    Measured: Predose (Baseline) up to 24 hours on Day 1

  10. Mean Change in Thrombin Generation Assay (TGA) Endogenous Thrombin Potential (ETP) Time to Peak in Part 1

    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.

    Measured: Predose (Baseline) up to 24 hours on Day 1

  11. Mean Change in Thrombin Generation Assay (TGA) Endogenous Thrombin Potential (ETP) Area Under Curve (AUC) in Part 1

    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.

    Measured: Predose (Baseline) up to 24 hours on Day 1

  12. Mean Change in Prothrombin Time (PT) in Part 1

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

    Measured: Predose (Baseline) up to 24 hours on Day 1

  13. Trough Plasma Concentration (Ctrough) in Part 2

    Ctrough is the trough plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose.

    Measured: Predose and up to 72 hrs postdose on Day 4

  14. Number of Participants With Adverse Events as a Measure of Safety and Tolerability

    An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

    Measured: Up to 37 Days (Part 1) and Up to 40 Days (Part 2)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Sep 2015 (estimated)
  2. Study start27 Aug 2015
  3. Primary completion17 Jun 2016
  4. Study completion17 Jun 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
158 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02561923
Sponsor's protocol ID
CR107832
Other IDs
39039039NAP1004
Status last verified
Jan 2025
First submitted
21 Aug 2015
Last updated
3 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Rivaroxaban, Tranexamic acid and Kcentra, a 4-factor PCC in people with Healthy, run by Janssen Scientific Affairs, LLC at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Blood Volume in Part 1 (time frame: Day-1 (Baseline) and 4 hour (hr) postdose on Day 1). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2025.

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