study of local administration of depotxa for reduced postsurgical bleeding in subjects undergoing tka

Conditions: Total Knee Arthroplasty

Summary: this is a phase 2, randomized, single-blind, active-controlled dose-ranging study in subjects scheduled to undergo total knee arthroplasty (tka).

approximately 60 subjects (15 per arm) are planned for enrollment. subjects will be randomized in a 1:1:1:1 ratio to receive either depotxa 400 mg, depotxa 800 mg, depotxa 1200 mg, or iv txa (cyklokapron® 1 gram).

Eligibility criteria:
inclusion criteria: 1. male or female, ≥18 years of age at screening. 2. scheduled to undergo elective unilateral open tka under general, spinal, or regional anesthesia. 3. american society of anesthesiology (asa) physical status 1, 2, or 3. 4. female subject must be surgically sterile; or at least 2 years postmenopausal; or have a monogamous partner who is surgically sterile; or practicing double-barrier contraception; or practicing abstinence (must agree to use double-barrier contraception in the event of sexual activity); or using an insertable, injectable, or transdermal, contraceptive approved by the fda for greater than 2 months prior to screening and commit to the use of an acceptable form of birth control for the duration of the study and for 30 days after completion of the study. 5. able to provide informed consent, adhere to the study visit schedule, and complete all study assessments. exclusion criteria: 1. currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration. 2. planned concurrent surgical procedure (e.g., bilateral tka). 3. prior open knee surgery on ipsilateral knee. prior arthroscopy is permitted. 4. subjects taking a medication with a known procoagulant effect (e.g., combination hormonal contraceptives, factor ix complex concentrates or anti-inhibitor coagulant concentrates, or all-trans retinoic acid). 5. contraindication or hypersensitivity to txa. 6. history of thrombosis or prior venous thromboembolism (vte). 7. known coagulopathy or active intravascular clotting. 8. prior myocardial infarction. 9. prior cardiovascular accident (stroke) or subarachnoid hemorrhage. 10. history of epilepsy. 11. presence of an intravascular stent. 12. history of impaired kidney function, chronic respiratory disease, rheumatoid arthritis, coagulopathy, or loss of sensation in extremities. 13. renal insufficiency (serum creatinine level \>2 mg/dl). 14. anemia (hb level \<10 g/dl). 15. uncontrolled anxiety, psychiatric, or neurological disorder that might interfere with study assessments. 16. acquired defective color vision. 17. malignancy in the last 2 years, with the exception of non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix. 18. suspected or known history of drug or alcohol abuse within the previous year. 19. body weight \ 44 kg/m2. 20. administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug, whichever is longer, prior to study drug administration, or planned administration of another investigational product or procedure during the subject's participation in this study.