Study of Local Administration of DepoTXA for Reduced Bleeding in Subjects Undergoing TKA

Approximately 45 subjects (15 per arm) are planned for enrollment. Subjects will be
randomized in a 1:1:1 ratio to receive either DepoTXA 800 mg, DepoTXA 1200 mg, or IV TXA
(Cyklokapron® 1 gram).

Inclusion Criteria:

1. Scheduled to undergo elective unilateral open TKA under general, spinal, or regional
anesthesia.

2. American Society of Anesthesiology (ASA) physical status 1, 2, or 3.

3. Currently receiving anticoagulation or antiplatelet therapy for cardiovascular disease
or thromboembolic risk.

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. Patients taking a medication with a known procoagulant effect (eg, combination
hormonal contraceptives, Factor IX complex concentrates or anti-inhibitor coagulant
concentrates, or all-trans retinoic acid).

5. Contraindication or hypersensitivity to TXA.

6. Known active intravascular clotting.

7. Prior subarachnoid hemorrhage.

8. History of epilepsy.

9. History of impaired kidney function, chronic respiratory disease, rheumatoid
arthritis, congenital coagulopathy, or loss of sensation in extremities.

10. Renal insufficiency as indicated by serum creatinine > upper limit of normal (by
central laboratory assessment).

11. Anemia (Hb level,10 g/dL)

12. Uncontrolled anxiety, psychiatric, or neurological disorder that might interfere with
study assessments.

13. Acquired defective color vision.

14. 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

15. Suspected or known history of drug or alcohol abuse within the previous year.

16. Body weight ,50 kg (110 pounds) or a body mass index .44 kg/m2.

17. 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
patient's participation in this study.