a study to assess the independent effects of 4-factor prothrombin complex concentrate and tranexamic acid on bleeding/pharmacodynamics in healthy participants

Conditions: Healthy

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.

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.

Eligibility criteria:
inclusion criteria: * 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 exclusion criteria: * 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 \ 140 or \ 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)

Keywords: healthy rivaroxaban xarelto