Total Knee Arthroplasty
Conditions
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).
Interventions
DRUGDepoTXA
DRUGTranexamic Acid
Sponsors
Pacira Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 \<50 kg (110 pounds) or a body mass index \>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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to Maximum Plasma Concentration (Tmax) | 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 Extrapolated to Infinity After Drug Administration | 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 | 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) | 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 | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Transfusion (Number of Units, Number of Units/Subject, Number of Subjects Transfused) | Day 60 | — |
| 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 | Numerical rating scale (NRS) at rest pain score (0 \[no pain\] to 10 \[worst possible pain\]) upon arrival at the PACU; at each in-hospital vital sign assessment beginning with the 2-hour assessment and ending with the 48-hour assessment; and the Day-7 follow-up visit. Summary is provided as area under the curve (AUC) of NRS from timepoint 0 to 24 hours, 0 to 48 hours, and 24 to 48 hours. |
| Number of Participants With 90˚ Passive and Active Knee Flexion | 24, 48, and 72 hours | — |
| 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 | Neurological assessment at 12, 24, 36, 48, 60, 72, and 96 hours after study drug administration |
| Incidence of Reoperation Due to Hematoma or Wound Dehiscence | Through day 60 | Number of subjects who underwent reoperation due to hematoma or wound dehiscence |
| 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 | Physical therapy assessment (Timed Up-and-Go (TUG) test) was conducted once postsurgically on 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 | Leg difference in change from baseline is calculated by = (Operated Leg Change from Baseline) - (Non-Operated Leg Change from Baseline) |
Countries
United States
Participant flow
Recruitment details
Participants were recruited between October 28, 2016 and October 12, 2017 at 4 US sites. The study was terminated on 27-Nov-2017 due to low enrollment.
Pre-assignment details
One patient was screened but was not randomized due to not meeting inclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| DepoTXA 400mg Single injection of DepoTXA 400 mg into the joint space via catheter prior to capsular closure | 4 |
| DepoTXA 800mg Single injection of DepoTXA 800 mg into the joint space via catheter prior to capsular closure | 3 |
| DepoTXA 1200mg Single injection of DepoTXA 1200 mg into the joint space via catheter prior to capsular closure | 4 |
| IV Tranexamic Acid (TXA) 1 g of IV TXA at the end of surgery | 4 |
| Total | 15 |
Baseline characteristics
| Characteristic | DepoTXA 800mg | Total | IV Tranexamic Acid (TXA) | DepoTXA 1200mg | DepoTXA 400mg |
|---|---|---|---|---|---|
| Age, Continuous | 66 years STANDARD_DEVIATION 1.73 | 61.8 years STANDARD_DEVIATION 6.19 | 58.0 years STANDARD_DEVIATION 6.16 | 59.3 years STANDARD_DEVIATION 5.38 | 65 years STANDARD_DEVIATION 7.12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 15 Participants | 4 Participants | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 12 Participants | 3 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Female | 2 Participants | 9 Participants | 2 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 6 Participants | 2 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 3 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 4 / 4 | 2 / 3 | 4 / 4 | 4 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 3 | 0 / 4 | 0 / 4 |
Outcome results
Primary
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.
Population: Pharmacokinetic (PK) analysis set: All subjects who received study drug, provided sufficient samples to allow for calculation of PK parameters required for analysis, and who did not have significant protocol deviations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DepoTXA 400mg | Area Under the Plasma Concentration-versus-time Curve From Time 0 Extrapolated to Infinity After Drug Administration | 46462.15 hr*ng/mL | Standard Deviation 6935.828 |
| DepoTXA 800mg | Area Under the Plasma Concentration-versus-time Curve From Time 0 Extrapolated to Infinity After Drug Administration | 106422.7 hr*ng/mL | Standard Deviation 42128.84 |
| DepoTXA 1200mg | Area Under the Plasma Concentration-versus-time Curve From Time 0 Extrapolated to Infinity After Drug Administration | 148806.2 hr*ng/mL | Standard Deviation 14137.74 |
| IV Tranexamic Acid (TXA) | Area Under the Plasma Concentration-versus-time Curve From Time 0 Extrapolated to Infinity After Drug Administration | 134602.2 hr*ng/mL | Standard Deviation 29975.88 |
Primary
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.
Population: Pharmacokinetic (PK) analysis set: All subjects who received study drug, provided sufficient samples to allow for calculation of PK parameters required for analysis, and who did not have significant protocol deviations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DepoTXA 400mg | Area Under the Plasma Concentration-versus-time Curve From Time 0 to the Last Collection Time After Drug Administration | 43784.71 hr*ng/mL | Standard Deviation 6463.22 |
| DepoTXA 800mg | Area Under the Plasma Concentration-versus-time Curve From Time 0 to the Last Collection Time After Drug Administration | 104546.5 hr*ng/mL | Standard Deviation 42813.2 |
| DepoTXA 1200mg | Area Under the Plasma Concentration-versus-time Curve From Time 0 to the Last Collection Time After Drug Administration | 143562.9 hr*ng/mL | Standard Deviation 13931.94 |
| IV Tranexamic Acid (TXA) | Area Under the Plasma Concentration-versus-time Curve From Time 0 to the Last Collection Time After Drug Administration | 131153.0 hr*ng/mL | Standard Deviation 27286.97 |
Primary
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.
Population: Pharmacokinetic (PK) analysis set: All subjects who received study drug, provided sufficient samples to allow for calculation of PK parameters required for analysis, and who did not have significant protocol deviations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DepoTXA 400mg | Maximum Plasma Concentration (Cmax) | 2775.0 ng/mL | Standard Deviation 741.96 |
| DepoTXA 800mg | Maximum Plasma Concentration (Cmax) | 7722.0 ng/mL | Standard Deviation 2015.25 |
| DepoTXA 1200mg | Maximum Plasma Concentration (Cmax) | 9827.0 ng/mL | Standard Deviation 1545.83 |
| IV Tranexamic Acid (TXA) | Maximum Plasma Concentration (Cmax) | 125390.0 ng/mL | Standard Deviation 154587.6 |
Primary
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.
Population: Pharmacokinetic (PK) analysis set: All subjects who received study drug, provided sufficient samples to allow for calculation of PK parameters required for analysis, and who did not have significant protocol deviations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DepoTXA 400mg | The Apparent Terminal Elimination Half-life | 14.679 hr | Standard Deviation 2.698 |
| DepoTXA 800mg | The Apparent Terminal Elimination Half-life | 21.132 hr | Standard Deviation 7.2508 |
| DepoTXA 1200mg | The Apparent Terminal Elimination Half-life | 20.956 hr | Standard Deviation 5.7276 |
| IV Tranexamic Acid (TXA) | The Apparent Terminal Elimination Half-life | 5.220 hr | Standard Deviation 0.854 |
Primary
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.
Population: Pharmacokinetic (PK) analysis set: All subjects who received study drug, provided sufficient samples to allow for calculation of PK parameters required for analysis, and who did not have significant protocol deviations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DepoTXA 400mg | The Apparent Terminal Elimination Rate Constant | 0.048 1/hr | Standard Deviation 0.0084 |
| DepoTXA 800mg | The Apparent Terminal Elimination Rate Constant | 0.035 1/hr | Standard Deviation 0.012 |
| DepoTXA 1200mg | The Apparent Terminal Elimination Rate Constant | 0.035 1/hr | Standard Deviation 0.0095 |
| IV Tranexamic Acid (TXA) | The Apparent Terminal Elimination Rate Constant | 0.136 1/hr | Standard Deviation 0.0261 |
Primary
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.
Population: Pharmacokinetic (PK) analysis set: All subjects who received study drug, provided sufficient samples to allow for calculation of PK parameters required for analysis, and who did not have significant protocol deviations
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DepoTXA 400mg | Time to Maximum Plasma Concentration (Tmax) | 1.6 hr | Standard Deviation 0.55 |
| DepoTXA 800mg | Time to Maximum Plasma Concentration (Tmax) | 1.5 hr | Standard Deviation 0.57 |
| DepoTXA 1200mg | Time to Maximum Plasma Concentration (Tmax) | 2.5 hr | Standard Deviation 0.96 |
| IV Tranexamic Acid (TXA) | Time to Maximum Plasma Concentration (Tmax) | 0.1 hr | Standard Deviation 0 |
Secondary
Area Under the Curve (AUC) of NRS From 0-24 Hours, 0-48 Hours, and 24-48 Hours
Numerical rating scale (NRS) at rest pain score (0 \[no pain\] to 10 \[worst possible pain\]) upon arrival at the PACU; at each in-hospital vital sign assessment beginning with the 2-hour assessment and ending with the 48-hour assessment; and the Day-7 follow-up visit. Summary is provided as area under the curve (AUC) of NRS from timepoint 0 to 24 hours, 0 to 48 hours, and 24 to 48 hours.
Time frame: Preoperative; arrival in Post-Anesthesia Care Unit (PACU); 2, 4, 6, 8, 12, 16, 24, 36, 48 hours, Day 7
Population: Efficacy analysis set: All subjects who received study drug and underwent planned surgery.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DepoTXA 400mg | Area Under the Curve (AUC) of NRS From 0-24 Hours, 0-48 Hours, and 24-48 Hours | AUC(24-48) | 6145.1 scores on a scale*hour | Standard Deviation 2786.3 |
| DepoTXA 400mg | Area Under the Curve (AUC) of NRS From 0-24 Hours, 0-48 Hours, and 24-48 Hours | AUC(0-48) | 11375.1 scores on a scale*hour | Standard Deviation 6159.89 |
| DepoTXA 400mg | Area Under the Curve (AUC) of NRS From 0-24 Hours, 0-48 Hours, and 24-48 Hours | AUC(0-24) | 5230.0 scores on a scale*hour | Standard Deviation 3416.48 |
| DepoTXA 800mg | Area Under the Curve (AUC) of NRS From 0-24 Hours, 0-48 Hours, and 24-48 Hours | AUC(24-48) | 7340.0 scores on a scale*hour | Standard Deviation 1880.1 |
| DepoTXA 800mg | Area Under the Curve (AUC) of NRS From 0-24 Hours, 0-48 Hours, and 24-48 Hours | AUC(0-24) | 4723.0 scores on a scale*hour | Standard Deviation 3242.87 |
| DepoTXA 800mg | Area Under the Curve (AUC) of NRS From 0-24 Hours, 0-48 Hours, and 24-48 Hours | AUC(0-48) | 12063.0 scores on a scale*hour | Standard Deviation 3331.38 |
| DepoTXA 1200mg | Area Under the Curve (AUC) of NRS From 0-24 Hours, 0-48 Hours, and 24-48 Hours | AUC(0-48) | 10859.5 scores on a scale*hour | Standard Deviation 4761.97 |
| DepoTXA 1200mg | Area Under the Curve (AUC) of NRS From 0-24 Hours, 0-48 Hours, and 24-48 Hours | AUC(0-24) | 5119.3 scores on a scale*hour | Standard Deviation 2587.32 |
| DepoTXA 1200mg | Area Under the Curve (AUC) of NRS From 0-24 Hours, 0-48 Hours, and 24-48 Hours | AUC(24-48) | 5740.3 scores on a scale*hour | Standard Deviation 2244.9 |
| IV Tranexamic Acid (TXA) | Area Under the Curve (AUC) of NRS From 0-24 Hours, 0-48 Hours, and 24-48 Hours | AUC(24-48) | 6530.5 scores on a scale*hour | Standard Deviation 2936.93 |
| IV Tranexamic Acid (TXA) | Area Under the Curve (AUC) of NRS From 0-24 Hours, 0-48 Hours, and 24-48 Hours | AUC(0-48) | 13406.8 scores on a scale*hour | Standard Deviation 5495.4 |
| IV Tranexamic Acid (TXA) | Area Under the Curve (AUC) of NRS From 0-24 Hours, 0-48 Hours, and 24-48 Hours | AUC(0-24) | 6876.3 scores on a scale*hour | Standard Deviation 2560.73 |
Secondary
Change in Knee and Thigh Measurements
Leg difference in change from baseline is calculated by = (Operated Leg Change from Baseline) - (Non-Operated Leg Change from Baseline)
Time frame: 48 hours and Day 7
Population: Efficacy analysis set: All subjects who received study drug and underwent planned surgery.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DepoTXA 400mg | Change in Knee and Thigh Measurements | Leg Difference in Change from Baseline in Thigh Circumference (cm) at 48 hours | 5.0 cm | Standard Deviation 4.73 |
| DepoTXA 400mg | Change in Knee and Thigh Measurements | Leg Difference in Change from Baseline in Thigh Circumference (cm) at Day 7 | 4.3 cm | Standard Deviation 1.7 |
| DepoTXA 400mg | Change in Knee and Thigh Measurements | Leg Difference in Change from Baseline in Knee Circumference at 48 hours | 4.1 cm | Standard Deviation 3.47 |
| DepoTXA 400mg | Change in Knee and Thigh Measurements | Leg Difference in Change from Baseline in Knee Circumference at Day 7 | 2.6 cm | Standard Deviation 3.2 |
| DepoTXA 800mg | Change in Knee and Thigh Measurements | Leg Difference in Change from Baseline in Thigh Circumference (cm) at Day 7 | 5.2 cm | Standard Deviation 6.17 |
| DepoTXA 800mg | Change in Knee and Thigh Measurements | Leg Difference in Change from Baseline in Knee Circumference at 48 hours | 5.8 cm | Standard Deviation 5.37 |
| DepoTXA 800mg | Change in Knee and Thigh Measurements | Leg Difference in Change from Baseline in Knee Circumference at Day 7 | 3.8 cm | Standard Deviation 8.25 |
| DepoTXA 800mg | Change in Knee and Thigh Measurements | Leg Difference in Change from Baseline in Thigh Circumference (cm) at 48 hours | 6.7 cm | Standard Deviation 6.37 |
| DepoTXA 1200mg | Change in Knee and Thigh Measurements | Leg Difference in Change from Baseline in Knee Circumference at 48 hours | 2.2 cm | Standard Deviation 4.85 |
| DepoTXA 1200mg | Change in Knee and Thigh Measurements | Leg Difference in Change from Baseline in Thigh Circumference (cm) at Day 7 | 0.8 cm | Standard Deviation 5.09 |
| DepoTXA 1200mg | Change in Knee and Thigh Measurements | Leg Difference in Change from Baseline in Knee Circumference at Day 7 | -1.4 cm | Standard Deviation 4.03 |
| DepoTXA 1200mg | Change in Knee and Thigh Measurements | Leg Difference in Change from Baseline in Thigh Circumference (cm) at 48 hours | 3.4 cm | Standard Deviation 4.54 |
| IV Tranexamic Acid (TXA) | Change in Knee and Thigh Measurements | Leg Difference in Change from Baseline in Knee Circumference at Day 7 | 4.3 cm | Standard Deviation 0.35 |
| IV Tranexamic Acid (TXA) | Change in Knee and Thigh Measurements | Leg Difference in Change from Baseline in Thigh Circumference (cm) at Day 7 | 3.3 cm | Standard Deviation 3.18 |
| IV Tranexamic Acid (TXA) | Change in Knee and Thigh Measurements | Leg Difference in Change from Baseline in Thigh Circumference (cm) at 48 hours | 6.1 cm | Standard Deviation 1.39 |
| IV Tranexamic Acid (TXA) | Change in Knee and Thigh Measurements | Leg Difference in Change from Baseline in Knee Circumference at 48 hours | 1.0 cm | Standard Deviation 5.25 |
Secondary
Incidence of Reoperation Due to Hematoma or Wound Dehiscence
Number of subjects who underwent reoperation due to hematoma or wound dehiscence
Time frame: Through day 60
Population: Safety analysis set: All subjects who received study drug treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DepoTXA 400mg | Incidence of Reoperation Due to Hematoma or Wound Dehiscence | 0 participants |
| DepoTXA 800mg | Incidence of Reoperation Due to Hematoma or Wound Dehiscence | 0 participants |
| DepoTXA 1200mg | Incidence of Reoperation Due to Hematoma or Wound Dehiscence | 0 participants |
| IV Tranexamic Acid (TXA) | Incidence of Reoperation Due to Hematoma or Wound Dehiscence | 0 participants |
Secondary
Incidence of Transfusion (Number of Units, Number of Units/Subject, Number of Subjects Transfused)
Time frame: Day 60
Population: Efficacy analysis set: All subjects who received study drug and underwent planned surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DepoTXA 400mg | Incidence of Transfusion (Number of Units, Number of Units/Subject, Number of Subjects Transfused) | 0 participants |
| DepoTXA 800mg | Incidence of Transfusion (Number of Units, Number of Units/Subject, Number of Subjects Transfused) | 0 participants |
| DepoTXA 1200mg | Incidence of Transfusion (Number of Units, Number of Units/Subject, Number of Subjects Transfused) | 0 participants |
| IV Tranexamic Acid (TXA) | Incidence of Transfusion (Number of Units, Number of Units/Subject, Number of Subjects Transfused) | 0 participants |
Secondary
Number of Participants With 90˚ Passive and Active Knee Flexion
Time frame: 24, 48, and 72 hours
Population: Efficacy analysis set: All subjects who received study drug and underwent planned surgery.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DepoTXA 400mg | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ active knee flexion at 48 hours | 0 participants |
| DepoTXA 400mg | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ active knee flexion at 24 hours | 0 participants |
| DepoTXA 400mg | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ active knee flexion at 72 hours | 1 participants |
| DepoTXA 400mg | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ passive knee flexion at 24 hours | 0 participants |
| DepoTXA 400mg | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ passive knee flexion at 48 hours | 1 participants |
| DepoTXA 400mg | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ passive knee flexion at 72 hours | 2 participants |
| DepoTXA 800mg | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ passive knee flexion at 48 hours | 0 participants |
| DepoTXA 800mg | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ active knee flexion at 48 hours | 0 participants |
| DepoTXA 800mg | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ active knee flexion at 72 hours | 0 participants |
| DepoTXA 800mg | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ active knee flexion at 24 hours | 0 participants |
| DepoTXA 800mg | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ passive knee flexion at 72 hours | 1 participants |
| DepoTXA 800mg | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ passive knee flexion at 24 hours | 1 participants |
| DepoTXA 1200mg | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ passive knee flexion at 72 hours | 0 participants |
| DepoTXA 1200mg | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ passive knee flexion at 48 hours | 0 participants |
| DepoTXA 1200mg | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ passive knee flexion at 24 hours | 0 participants |
| DepoTXA 1200mg | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ active knee flexion at 72 hours | 0 participants |
| DepoTXA 1200mg | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ active knee flexion at 24 hours | 0 participants |
| DepoTXA 1200mg | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ active knee flexion at 48 hours | 0 participants |
| IV Tranexamic Acid (TXA) | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ active knee flexion at 24 hours | 0 participants |
| IV Tranexamic Acid (TXA) | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ active knee flexion at 48 hours | 1 participants |
| IV Tranexamic Acid (TXA) | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ passive knee flexion at 72 hours | 0 participants |
| IV Tranexamic Acid (TXA) | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ active knee flexion at 72 hours | 0 participants |
| IV Tranexamic Acid (TXA) | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ passive knee flexion at 24 hours | 1 participants |
| IV Tranexamic Acid (TXA) | Number of Participants With 90˚ Passive and Active Knee Flexion | Number of subjects who had 90˚ passive knee flexion at 48 hours | 1 participants |
Secondary
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
Neurological assessment at 12, 24, 36, 48, 60, 72, and 96 hours after study drug administration
Time frame: 12, 24, 36, 48, 60, 72, and 96 hours after study drug administration
Population: Safety analysis set: All subjects who received study drug treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DepoTXA 400mg | 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 | Number of subjects who had any of the neurologic events at baseline | 0 participants |
| DepoTXA 400mg | 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 | Number of subjects who had any of the neurologic events at 12 hours | 0 participants |
| DepoTXA 400mg | 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 | Number of subjects who had any of the neurologic events at 24 hours | 0 participants |
| DepoTXA 400mg | 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 | Number of subjects who had any of the neurologic events at 36 hours | 0 participants |
| DepoTXA 400mg | 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 | Number of subjects who had any of the neurologic events at 48 hours | 0 participants |
| DepoTXA 400mg | 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 | Number of subjects who had any of the neurologic events at 60 hours | 0 participants |
| DepoTXA 400mg | 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 | Number of subjects who had any of the neurologic events at 72 hours | 0 participants |
| DepoTXA 400mg | 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 | Number of subjects who had any of the neurologic events at 96 hours | 0 participants |
| DepoTXA 800mg | 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 | Number of subjects who had any of the neurologic events at 60 hours | 0 participants |
| DepoTXA 800mg | 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 | Number of subjects who had any of the neurologic events at 48 hours | 0 participants |
| DepoTXA 800mg | 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 | Number of subjects who had any of the neurologic events at 12 hours | 0 participants |
| DepoTXA 800mg | 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 | Number of subjects who had any of the neurologic events at 96 hours | 0 participants |
| DepoTXA 800mg | 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 | Number of subjects who had any of the neurologic events at 72 hours | 0 participants |
| DepoTXA 800mg | 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 | Number of subjects who had any of the neurologic events at 36 hours | 0 participants |
| DepoTXA 800mg | 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 | Number of subjects who had any of the neurologic events at 24 hours | 0 participants |
| DepoTXA 800mg | 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 | Number of subjects who had any of the neurologic events at baseline | 0 participants |
| DepoTXA 1200mg | 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 | Number of subjects who had any of the neurologic events at 72 hours | 0 participants |
| DepoTXA 1200mg | 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 | Number of subjects who had any of the neurologic events at 24 hours | 0 participants |
| DepoTXA 1200mg | 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 | Number of subjects who had any of the neurologic events at 36 hours | 0 participants |
| DepoTXA 1200mg | 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 | Number of subjects who had any of the neurologic events at 48 hours | 0 participants |
| DepoTXA 1200mg | 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 | Number of subjects who had any of the neurologic events at 60 hours | 0 participants |
| DepoTXA 1200mg | 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 | Number of subjects who had any of the neurologic events at 96 hours | 0 participants |
| DepoTXA 1200mg | 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 | Number of subjects who had any of the neurologic events at baseline | 0 participants |
| DepoTXA 1200mg | 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 | Number of subjects who had any of the neurologic events at 12 hours | 0 participants |
| IV Tranexamic Acid (TXA) | 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 | Number of subjects who had any of the neurologic events at 24 hours | 0 participants |
| IV Tranexamic Acid (TXA) | 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 | Number of subjects who had any of the neurologic events at 36 hours | 0 participants |
| IV Tranexamic Acid (TXA) | 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 | Number of subjects who had any of the neurologic events at 12 hours | 0 participants |
| IV Tranexamic Acid (TXA) | 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 | Number of subjects who had any of the neurologic events at baseline | 0 participants |
| IV Tranexamic Acid (TXA) | 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 | Number of subjects who had any of the neurologic events at 48 hours | 0 participants |
| IV Tranexamic Acid (TXA) | 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 | Number of subjects who had any of the neurologic events at 96 hours | 0 participants |
| IV Tranexamic Acid (TXA) | 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 | Number of subjects who had any of the neurologic events at 72 hours | 0 participants |
| IV Tranexamic Acid (TXA) | 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 | Number of subjects who had any of the neurologic events at 60 hours | 0 participants |
Secondary
Time to Complete Timed Up-and-Go (TUG) Test
Physical therapy assessment (Timed Up-and-Go (TUG) test) was conducted once postsurgically on Day 1; at approximately 8:00 am and 8:00 pm (±2 hours) daily from Day 2 through hospital discharge; and on Day 7
Time frame: Day 1; at approximately 8:00 am and 8:00 pm (±2 hours) daily from Day 2 through hospital discharge; and on Day 7
Population: Efficacy analysis set: All subjects who received study drug and underwent planned surgery.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DepoTXA 400mg | Time to Complete Timed Up-and-Go (TUG) Test | Day 2 -Discharge | 44.3 seconds | Standard Deviation 6.03 |
| DepoTXA 400mg | Time to Complete Timed Up-and-Go (TUG) Test | Day 1 | 50.0 seconds | — |
| DepoTXA 400mg | Time to Complete Timed Up-and-Go (TUG) Test | Day 7 | 28.4 seconds | Standard Deviation 11.64 |
| DepoTXA 400mg | Time to Complete Timed Up-and-Go (TUG) Test | Day 2 - AM | 47.5 seconds | Standard Deviation 10.61 |
| DepoTXA 400mg | Time to Complete Timed Up-and-Go (TUG) Test | Day 2- PM | 48.0 seconds | Standard Deviation 14.14 |
| DepoTXA 400mg | Time to Complete Timed Up-and-Go (TUG) Test | Baseline | 16.4 seconds | Standard Deviation 4.25 |
| DepoTXA 800mg | Time to Complete Timed Up-and-Go (TUG) Test | Day 2 - AM | 90.0 seconds | Standard Deviation 7.07 |
| DepoTXA 800mg | Time to Complete Timed Up-and-Go (TUG) Test | Baseline | 18.1 seconds | Standard Deviation 10.73 |
| DepoTXA 800mg | Time to Complete Timed Up-and-Go (TUG) Test | Day 2 -Discharge | 51.1 seconds | Standard Deviation 32.85 |
| DepoTXA 800mg | Time to Complete Timed Up-and-Go (TUG) Test | Day 2- PM | 85.0 seconds | Standard Deviation 7.07 |
| DepoTXA 800mg | Time to Complete Timed Up-and-Go (TUG) Test | Day 7 | 51.2 seconds | Standard Deviation 32.89 |
| DepoTXA 800mg | Time to Complete Timed Up-and-Go (TUG) Test | Day 1 | 80.0 seconds | — |
| DepoTXA 1200mg | Time to Complete Timed Up-and-Go (TUG) Test | Day 7 | 32.3 seconds | Standard Deviation 15.72 |
| DepoTXA 1200mg | Time to Complete Timed Up-and-Go (TUG) Test | Day 1 | 40.0 seconds | Standard Deviation 7.07 |
| DepoTXA 1200mg | Time to Complete Timed Up-and-Go (TUG) Test | Day 2- PM | 69.0 seconds | Standard Deviation 25.94 |
| DepoTXA 1200mg | Time to Complete Timed Up-and-Go (TUG) Test | Day 2 - AM | 66.7 seconds | Standard Deviation 23.63 |
| DepoTXA 1200mg | Time to Complete Timed Up-and-Go (TUG) Test | Baseline | 14.6 seconds | Standard Deviation 8.97 |
| DepoTXA 1200mg | Time to Complete Timed Up-and-Go (TUG) Test | Day 2 -Discharge | 61.3 seconds | Standard Deviation 31.76 |
| IV Tranexamic Acid (TXA) | Time to Complete Timed Up-and-Go (TUG) Test | Day 2 - AM | 85.0 seconds | Standard Deviation 21.88 |
| IV Tranexamic Acid (TXA) | Time to Complete Timed Up-and-Go (TUG) Test | Baseline | 15.4 seconds | Standard Deviation 6.92 |
| IV Tranexamic Acid (TXA) | Time to Complete Timed Up-and-Go (TUG) Test | Day 1 | 80.0 seconds | — |
| IV Tranexamic Acid (TXA) | Time to Complete Timed Up-and-Go (TUG) Test | Day 7 | 13.1 seconds | — |
| IV Tranexamic Acid (TXA) | Time to Complete Timed Up-and-Go (TUG) Test | Day 2- PM | 41.0 seconds | Standard Deviation 6.08 |
| IV Tranexamic Acid (TXA) | Time to Complete Timed Up-and-Go (TUG) Test | Day 2 -Discharge | 40.0 seconds | Standard Deviation 0 |