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Slow Enrollment
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DepoTXA 400mg | Experimental | 400mg Intracapsular at the end of surgery one time |
|
| DepoTXA 800mg | Experimental | 800mg Intracapsular at the end of surgery one time |
|
| DepoTXA 1200mg | Experimental | 1200mg Intracapsular at the end of surgery one time |
|
| IV Tranexamic acid (TXA) | Active Comparator | 1 g of IV TXA at the end of surgery |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DepoTXA | Drug |
| ||
| Tranexamic Acid |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | |
| 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. | |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 12, 24, 36, 48, 60, 72, and 96 hours after study drug administration |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hassan Danesi, MD | Pacira Pharmaceuticals, Inc | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ortho Arizona | Gilbert | Arizona | 85296 | United States | ||
| University of Miami Hospital |
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One patient was screened but was not randomized due to not meeting inclusion criteria.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | DepoTXA 400mg | Single injection of DepoTXA 400 mg into the joint space via catheter prior to capsular closure |
| FG001 | DepoTXA 800mg | Single injection of DepoTXA 800 mg into the joint space via catheter prior to capsular closure |
| FG002 | DepoTXA 1200mg | Single injection of DepoTXA 1200 mg into the joint space via catheter prior to capsular closure |
| FG003 | IV Tranexamic Acid (TXA) | 1 g of IV TXA at the end of surgery |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Safety analysis set: All subjects who received study drug
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| ID | Title | Description |
|---|---|---|
| BG000 | DepoTXA 400mg | Single injection of DepoTXA 400 mg into the joint space via catheter prior to capsular closure |
| BG001 | DepoTXA 800mg | Single injection of DepoTXA 800 mg into the joint space via catheter prior to capsular closure |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Plasma Concentration-versus-time Curve From Time 0 Extrapolated to Infinity After Drug Administration | 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 | Posted | Mean | Standard Deviation | hr*ng/mL | 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. |
|
From screening to postsurgical day 60
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (eg, abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug without any judgment about causality. Serious AEs were defined as per clinicaltrials.gov.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | DepoTXA 400mg | Single injection of DepoTXA 400 mg into the joint space via catheter prior to capsular closure |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA version 19.1 | Systematic Assessment |
This study was terminated on 27-Nov-2017 due to low enrollment; small sample sizes make data interpretation difficult.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pacira Medical Information | Pacira Pharmaceuticals, Inc. | 1-855-793-9727 | MedInfo@pacira.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 27, 2017 | Sep 17, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 29, 2018 | Sep 17, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D014148 | Tranexamic Acid |
| ID | Term |
|---|---|
| D003509 | Cyclohexanecarboxylic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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| Drug |
|
| Incidence of Reoperation Due to Hematoma or Wound Dehiscence |
Number of subjects who underwent reoperation due to hematoma or wound dehiscence |
| Through day 60 |
| 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 | 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 | 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 | Leg difference in change from baseline is calculated by = (Operated Leg Change from Baseline) - (Non-Operated Leg Change from Baseline) | 48 hours and Day 7 |
| 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. | Preoperative; arrival in Post-Anesthesia Care Unit (PACU); 2, 4, 6, 8, 12, 16, 24, 36, 48 hours, Day 7 |
| Miami |
| Florida |
| 33136 |
| United States |
| Kendall Regional Medical Center | Miami | Florida | 33175 | United States |
| Ohio State University/Wexner Medical Center | Columbus | Ohio | 43210 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| BG002 | DepoTXA 1200mg | Single injection of DepoTXA 1200 mg into the joint space via catheter prior to capsular closure |
| BG003 | IV Tranexamic Acid (TXA) | 1 g of IV TXA at the end of surgery |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
Single injection of DepoTXA 800 mg into the joint space via catheter prior to capsular closure |
| OG002 | DepoTXA 1200mg | Single injection of DepoTXA 1200 mg into the joint space via catheter prior to capsular closure |
| OG003 | IV Tranexamic Acid (TXA) | 1 g of IV TXA at the end of surgery |
|
|
| Primary | Area Under the Plasma Concentration-versus-time Curve From Time 0 to the Last Collection Time After Drug Administration | 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 | Posted | Mean | Standard Deviation | hr*ng/mL | 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. |
|
|
|
| Primary | Maximum Plasma Concentration (Cmax) | 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 | Posted | Mean | Standard Deviation | ng/mL | 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. |
|
|
|
| Primary | Time to Maximum Plasma Concentration (Tmax) | 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 | Posted | Mean | Standard Deviation | hr | 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. |
|
|
|
| Primary | The Apparent Terminal Elimination Rate Constant | 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 | Posted | Mean | Standard Deviation | 1/hr | 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. |
|
|
|
| Primary | The Apparent Terminal Elimination Half-life | 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 | Posted | Mean | Standard Deviation | hr | 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 | 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 | Safety analysis set: All subjects who received study drug treatment | Posted | Number | participants | 12, 24, 36, 48, 60, 72, and 96 hours after study drug administration |
|
|
|
| Secondary | Incidence of Reoperation Due to Hematoma or Wound Dehiscence | Number of subjects who underwent reoperation due to hematoma or wound dehiscence | Safety analysis set: All subjects who received study drug treatment | Posted | Number | participants | Through day 60 |
|
|
|
| Secondary | Incidence of Transfusion (Number of Units, Number of Units/Subject, Number of Subjects Transfused) | Efficacy analysis set: All subjects who received study drug and underwent planned surgery. | Posted | Number | participants | Day 60 |
|
|
|
| Secondary | Number of Participants With 90˚ Passive and Active Knee Flexion | Efficacy analysis set: All subjects who received study drug and underwent planned surgery. | Posted | Number | participants | 24, 48, and 72 hours |
|
|
|
| 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 | Efficacy analysis set: All subjects who received study drug and underwent planned surgery. | Posted | Mean | Standard Deviation | seconds | Day 1; at approximately 8:00 am and 8:00 pm (±2 hours) daily from Day 2 through hospital discharge; and on Day 7 |
|
|
|
| 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) | Efficacy analysis set: All subjects who received study drug and underwent planned surgery. | Posted | Mean | Standard Deviation | cm | 48 hours and Day 7 |
|
|
|
| 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. | Efficacy analysis set: All subjects who received study drug and underwent planned surgery. | Posted | Mean | Standard Deviation | scores on a scale*hour | Preoperative; arrival in Post-Anesthesia Care Unit (PACU); 2, 4, 6, 8, 12, 16, 24, 36, 48 hours, Day 7 |
|
|
|
| 0 |
| 4 |
| 0 |
| 4 |
| 4 |
| 4 |
| EG001 | DepoTXA 800mg | Single injection of DepoTXA 800 mg into the joint space via catheter prior to capsular closure | 0 | 3 | 0 | 3 | 2 | 3 |
| EG002 | DepoTXA 1200mg | Single injection of DepoTXA 1200 mg into the joint space via catheter prior to capsular closure | 0 | 4 | 0 | 4 | 4 | 4 |
| EG003 | IV Tranexamic Acid (TXA) | 1 g of IV TXA at the end of surgery | 0 | 4 | 0 | 4 | 4 | 4 |
| Postprocedural hemorrhage | Injury, poisoning and procedural complications | MedDRA version 19.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA version 19.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA version 19.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA version 19.1 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA version 19.1 | Systematic Assessment |
|
| Gout | Metabolism and nutrition disorders | MedDRA version 19.1 | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | MedDRA version 19.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA version 19.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 19.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA version 19.1 | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA version 19.1 | Systematic Assessment |
|
| Hypoesthesia | Nervous system disorders | MedDRA version 19.1 | Systematic Assessment |
|
| Sinus arrhythmia | Cardiac disorders | MedDRA version 19.1 | Systematic Assessment |
|
Institution and investigator shall reasonably cooperate with Pacira to prepare abstract and manuscript reporting primary results within 90 and 120 days, respectively, of single and/or pooled analysis final CSR and shall publish no other trial results within 12 months after completion of final CSR. Institution shall submit all proposed written materials related to the trial ≥60 days before submission for presentation/publication. Pacira may embargo publication for an additional 90 days.
| Number of subjects who had any of the neurologic events at 12 hours |
|
| Number of subjects who had any of the neurologic events at 24 hours |
|
| Number of subjects who had any of the neurologic events at 36 hours |
|
| Number of subjects who had any of the neurologic events at 48 hours |
|
| Number of subjects who had any of the neurologic events at 60 hours |
|
| Number of subjects who had any of the neurologic events at 72 hours |
|
| Number of subjects who had any of the neurologic events at 96 hours |
|
| Number of subjects who had 90˚ active knee flexion at 48 hours |
|
| Number of subjects who had 90˚ active knee flexion at 72 hours |
|
| Number of subjects who had 90˚ passive knee flexion at 24 hours |
|
| Number of subjects who had 90˚ passive knee flexion at 48 hours |
|
| Number of subjects who had 90˚ passive knee flexion at 72 hours |
|
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| Day 1 |
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| Day 2 - AM |
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| Day 2- PM |
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| Day 2 -Discharge |
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| Day 7 |
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| Leg Difference in Change from Baseline in Thigh Circumference (cm) at Day 7 |
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| Leg Difference in Change from Baseline in Knee Circumference at 48 hours |
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| Leg Difference in Change from Baseline in Knee Circumference at Day 7 |
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| AUC(0-48) |
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| AUC(24-48) |
|