A Randomized, Single-Blind, Active-Controlled, Dose-Ranging Study to Evaluate the Pharmacokinetics, Safety, and Efficacy of Local Administration of DepoTXA for Reduced Postsurgical Bleeding in Subjects Undergoing Total Knee Arthroplasty
Overview
- Phase
- Phase 2
- Intervention
- DepoTXA
- Conditions
- Total Knee Arthroplasty
- Sponsor
- Pacira Pharmaceuticals, Inc
- Enrollment
- 16
- Locations
- 5
- Primary Endpoint
- Area Under the Plasma Concentration-versus-time Curve From Time 0 Extrapolated to Infinity After Drug Administration
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
Brief Summary
This is a Phase 2, randomized, single-blind, active-controlled dose-ranging study in subjects scheduled to undergo total knee arthroplasty (TKA).
Detailed Description
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female, ≥18 years of age at screening.
- •Scheduled to undergo elective unilateral open TKA under general, spinal, or regional anesthesia.
- •American Society of Anesthesiology (ASA) physical status 1, 2, or
- •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.
- •Able to provide informed consent, adhere to the study visit schedule, and complete all study assessments.
Exclusion Criteria
- •Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration.
- •Planned concurrent surgical procedure (e.g., bilateral TKA).
- •Prior open knee surgery on ipsilateral knee. Prior arthroscopy is permitted.
- •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).
- •Contraindication or hypersensitivity to TXA.
- •History of thrombosis or prior Venous thromboembolism (VTE).
- •Known coagulopathy or active intravascular clotting.
- •Prior myocardial infarction.
- •Prior cardiovascular accident (stroke) or subarachnoid hemorrhage.
- •History of epilepsy.
Arms & Interventions
DepoTXA 400mg
400mg Intracapsular at the end of surgery one time
Intervention: DepoTXA
DepoTXA 800mg
800mg Intracapsular at the end of surgery one time
Intervention: DepoTXA
DepoTXA 1200mg
1200mg Intracapsular at the end of surgery one time
Intervention: DepoTXA
IV Tranexamic acid (TXA)
1 g of IV TXA at the end of surgery
Intervention: Tranexamic Acid
Outcomes
Primary Outcomes
Area Under the Plasma Concentration-versus-time Curve From Time 0 Extrapolated to Infinity After Drug Administration
Time Frame: Baseline; 5, 15, and 30 min; at 1, 2, 4, 6, 8, 12, 16, and 24 hours after study drug administration for all treatment groups. Additional blood samples were collected at 36, 48, 60, 72, and 96 hours for DepoTXA-treated subjects.
Area Under the Plasma Concentration-versus-time Curve From Time 0 to the Last Collection Time After Drug Administration
Time Frame: Baseline; 5, 15, and 30 min; at 1, 2, 4, 6, 8, 12, 16, and 24 hours after study drug administration for all treatment groups. Additional blood samples were collected at 36, 48, 60, 72, and 96 hours for DepoTXA-treated subjects.
The Apparent Terminal Elimination Rate Constant
Time Frame: Baseline; 5, 15, and 30 min; at 1, 2, 4, 6, 8, 12, 16, and 24 hours after study drug administration for all treatment groups. Additional blood samples were collected at 36, 48, 60, 72, and 96 hours for DepoTXA-treated subjects.
Maximum Plasma Concentration (Cmax)
Time Frame: Baseline; 5, 15, and 30 min; at 1, 2, 4, 6, 8, 12, 16, and 24 hours after study drug administration for all treatment groups. Additional blood samples were collected at 36, 48, 60, 72, and 96 hours for DepoTXA-treated subjects.
Time to Maximum Plasma Concentration (Tmax)
Time Frame: Baseline; 5, 15, and 30 min; at 1, 2, 4, 6, 8, 12, 16, and 24 hours after study drug administration for all treatment groups. Additional blood samples were collected at 36, 48, 60, 72, and 96 hours for DepoTXA-treated subjects.
The Apparent Terminal Elimination Half-life
Time Frame: Baseline; 5, 15, and 30 min; at 1, 2, 4, 6, 8, 12, 16, and 24 hours after study drug administration for all treatment groups. Additional blood samples were collected at 36, 48, 60, 72, and 96 hours for DepoTXA-treated subjects.
Secondary Outcomes
- Incidence of Reoperation Due to Hematoma or Wound Dehiscence(Through day 60)
- Summary of Neurological Assessments (Proportion of Subjects Who Were Oriented and Proportion of Subjects Who Had Any of the Neurologic Events) at Each Assessed Timepoint(12, 24, 36, 48, 60, 72, and 96 hours after study drug administration)
- Incidence of Transfusion (Number of Units, Number of Units/Subject, Number of Subjects Transfused)(Day 60)
- Number of Participants With 90˚ Passive and Active Knee Flexion(24, 48, and 72 hours)
- Time to Complete Timed Up-and-Go (TUG) Test(Day 1; at approximately 8:00 am and 8:00 pm (±2 hours) daily from Day 2 through hospital discharge; and on Day 7)
- Change in Knee and Thigh Measurements(48 hours and Day 7)
- Area Under the Curve (AUC) of NRS From 0-24 Hours, 0-48 Hours, and 24-48 Hours(Preoperative; arrival in Post-Anesthesia Care Unit (PACU); 2, 4, 6, 8, 12, 16, 24, 36, 48 hours, Day 7)