Analgesia
Conditions
Keywords
total knee arthroplasty, postoperative pain, multimodal analgesia
Brief summary
Phase 3b, open-label single-arm study in which all subjects receive HTX-011 as part of a scheduled non-opioid MMA regimen.
Interventions
DRUGHTX-011
Dual-acting local anesthetic. Dose 1.
DRUGIbuprofen
NSAID.
DRUGAcetaminophen
Analgesic.
DRUGCelecoxib
NSAID.
DRUG+/- Bupivacaine HCl
Local anesthetic.
DEVICELuer Lock Applicator
Applicator for instillation.
Sponsors
Heron Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Is scheduled to undergo primary unilateral TKA under spinal anesthesia. * Has not previously undergone TKA in either knee. * Has an American Society of Anesthesiologists (ASA) Physical Status of I, II, or III. * Is able to walk at least 20 feet with optional use of a 4-legged walker for balance. * Female subjects are eligible only if not pregnant, not lactating, not planning to become pregnant during the study, sterile; or is at least 2 years post-menopausal; or is in a monogamous relationship with a partner who is surgically sterile; or using acceptable contraceptives.
Exclusion criteria
* Has a planned concurrent surgical procedure. * Has other pre-existing concurrent acute or chronic painful physical/restrictive condition expected to require analgesic treatment in the postoperative period for pain. * Has a contraindication or a known or suspected history of hypersensitivity or clinically significant idiosyncratic reaction to required study medications. * Using or expected to use Factor IX Complex or anti-inhibitor coagulant concentrates during the study. * Has known or suspected daily use of opioids for 7 or more consecutive days within the previous 6 months. * Has taken NSAIDs within 10 days prior to the scheduled surgery with the exception of subjects on low-dose (≤100 mg) daily acetylsalicylic acid for cardioprotection. * Has taken opioids within 24 hours prior to the scheduled surgery (3 days for long-acting). * Has been administered bupivacaine within 5 days prior to the scheduled surgery. * Has been administered any local anesthetic within 72 hours prior to the scheduled surgery. * Has initiated treatment with medications within 1 month prior to study drug administration that can impact pain control. * Has been administered systemic steroids within 5 half-lives or 10 days prior to administration of study drug. * Received an investigational product or device in a clinical trial within 30 days or within 5 elimination half lives. * Has a known or suspected history of drug abuse, a positive drug screen on the day of surgery, or a recent history of alcohol abuse. * Has a medical condition such that, in the opinion of the Investigator, participating in the study would pose a health risk to the subject or confound the postoperative assessments. * Is currently undergoing treatment for hepatitis B, hepatitis C, or HIV. * Has uncontrolled anxiety, psychiatric, or neurological disorder that, in the opinion of the Investigator, might interfere with study assessments. * Has acquired defective color vision or acute gastrointestinal ulcers, either of which could interfere with scheduled study medications. * Has any chronic neuromuscular deficit of either femoral nerve function or thigh musculature. * Has any chronic condition or disease that would compromise neurological or vascular assessments. * Had a malignancy in the last year, with the exception of nonmetastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix. * Has undergone 3 or more surgeries within 12 months. * Has a body mass index (BMI) \>39 kg/m2.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Area Under the Curve (AUC) of the Visual Analogue Scale (VAS). | 12 through 48 hours | The Visual Analog Scale (VAS) consists of a straight 10-cm line that represents pain ranging from "no pain" to "pain as bad as it could be". Subjects were asked to mark their current pain level on the line. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean AUC of VAS Scores. | 72 hours | The Visual Analog Scale (VAS) consists of a straight 10-cm line that represents pain ranging from "no pain" to "pain as bad as it could be". Subjects were asked to mark their current pain level on the line. |
| Mean AUC of the NRS of Pain Intensity at Rest (NRS-R). | 72 hours | Pain intensity scores are assessed using an 11-point Numeric Rating Scale (NRS) (0-10) where 0 represents "no pain" and 10 represents "worst pain". NRS scores are measured at rest. |
| Percentage of Subjects With Severe Pain. | 24 hours, 48 hours, 72 hours | Severe Pain defined as a VAS score ≥7.5 cm. |
| Mean Total Postoperative Opioid Consumption (in IV Morphine Milligram Equivalents [MME]). | 72 hours | — |
| Percentage of Subjects Who Are Opioid-free | 72 Hours to Day 11 | — |
| Percentage of Subjects Who Are Opioid-free Through 72 Hours Who Remain Opioid-free Through Day 11. | 72 hours through Day 11 | — |
| Median Time to First Opioid Rescue Medication. | Through 72 hours | — |
| Percentage of Subjects Who do Not Receive an Opioid Prescription at Discharge. | 72 hours | — |
| Percentage of Subjects Who do Not Receive an Opioid Prescription Between Discharge and the Day 11 Visit. | 72 hours through Day 11 | — |
| Percentage of Subjects Achieving a Score of "Good" or Better (>1) Pain Control Based on Patient Global Assessment (PGA). | 24 hours, 48 hours, 72 hours, Day 11 | Patient's Global Assessment (PGA) of pain control is a 4-point scale in which subjects rate how well their pain has been controlled (0 = Poor; 1 = Fair; 2 = Good; 3 = Excellent). |
| Median Time to First Ambulation Postsurgery. | 72 hours | — |
| Percentage of Subjects Unable to Participate in Each Rehabilitation Session Because of Pain. | 72 hours | — |
| Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24, hours, 36 hours, 48 hours, 60 hours, 72 hours | Subjects were assessed for readiness for discharge using the Modified Post-Anesthesia Discharge Scoring System (MPADSS) that assesses 5 clinical variables: vital signs, ambulation, nausea/vomiting, pain, and surgical bleeding, each on a 3-point scale of 0, 1, or 2 with 0 being the worst score and 2 being the best score. Subjects with an MPADSS score of 9 or 10 were considered ready for discharge. |
| Percentage of Subjects Who Are Discharged Home vs to a Skilled Nursing Facility. | 72 hours | Number Analyzed represents Subjects who were discharged home. |
| Mean Overall Benefit of Analgesia Score (OBAS). | 24 hours, 48 hours, 72 hours, Day 11 | Subjects were questioned about their overall benefit of analgesia. Overall benefit of analgesia score (OBAS) assesses current pain at rest, vomiting, itching, sweating, freezing, dizziness, and overall satisfaction with postoperative pain during the previous 24 hours. To calculate the OBAS score, each of the subscale scores (0=minimum; 4=maximum) are summed for a combined OBAS score. Possible scores could range from 0 to 28 with a lower score indicating greater benefit. |
| Mean Total TSQM-9 Score | 72 hours through Day 11 | The Treatment Satisfaction Questionnaire for Medication (TSQM-9) contains 9 items assessing Effectiveness, Convenience, and Global Satisfaction domains. Responses to items are rated on a 5-point or 7-point rating scale. Scores for each domain are computed by adding the TSQM items in each domain and then transforming the values in to a composite score ranging from 0 to 100, with higher scores representing higher satisfaction. |
| Maximum Concentration (Cmax) | 72 hours | — |
| Time of Occurrence of Maximum Concentration (Tmax) | 72 hours | — |
Countries
United States
Participant flow
Pre-assignment details
Subjects in Cohort 1 and Cohort 2 received the same Assigned Intervention (ie, HTX-011 400 mg/12 mg + celecoxib-containing MMA regimen) and results are pooled for the purpose of this Results Section.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 and Cohort 2 (Pooled) HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + celecoxib-containing MMA regimen. | 66 |
| Cohort 3: Group A HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg + celecoxib-containing MMA regimen. | 14 |
| Cohort 3: Group B HTX-011 (bupivacaine/meloxicam), 300 mg/9 mg and 100 mg bupivacaine HCl + celecoxib-containing MMA regimen. | 16 |
| Cohort 4 HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg + ibuprofen-containing MMA regimen. | 20 |
| Total | 116 |
Baseline characteristics
| Characteristic | Cohort 3: Group A | Cohort 3: Group B | Cohort 4 | Total | Cohort 1 and Cohort 2 (Pooled) |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 10 Participants | 13 Participants | 62 Participants | 31 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 7 Participants | 54 Participants | 35 Participants |
| Age, Continuous | 62.4 years STANDARD_DEVIATION 8.88 | 66.8 years STANDARD_DEVIATION 9.81 | 69.0 years STANDARD_DEVIATION 8.82 | 65.1 years STANDARD_DEVIATION 9.64 | 64.0 years STANDARD_DEVIATION 9.64 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 5 Participants | 29 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 13 Participants | 15 Participants | 87 Participants | 46 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 | 3 Participants | 3 Participants | 5 Participants | 17 Participants | 6 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 11 Participants | 13 Participants | 15 Participants | 98 Participants | 59 Participants |
| Region of Enrollment United States | 14 participants | 16 participants | 20 participants | 116 participants | 66 participants |
| Sex: Female, Male Female | 4 Participants | 12 Participants | 12 Participants | 65 Participants | 37 Participants |
| Sex: Female, Male Male | 10 Participants | 4 Participants | 8 Participants | 51 Participants | 29 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 / 66 | 0 / 14 | 0 / 16 | 0 / 20 |
| other Total, other adverse events | 56 / 66 | 12 / 14 | 14 / 16 | 15 / 20 |
| serious Total, serious adverse events | 2 / 66 | 0 / 14 | 0 / 16 | 2 / 20 |
Outcome results
Primary
Mean Area Under the Curve (AUC) of the Visual Analogue Scale (VAS).
The Visual Analog Scale (VAS) consists of a straight 10-cm line that represents pain ranging from no pain to pain as bad as it could be. Subjects were asked to mark their current pain level on the line.
Time frame: 12 through 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 and Cohort 2 (Pooled) | Mean Area Under the Curve (AUC) of the Visual Analogue Scale (VAS). | 155.57 pain intensity score*hr | Standard Deviation 95.651 |
| Cohort 3: Group A | Mean Area Under the Curve (AUC) of the Visual Analogue Scale (VAS). | 185.27 pain intensity score*hr | Standard Deviation 86.898 |
| Cohort 3: Group B | Mean Area Under the Curve (AUC) of the Visual Analogue Scale (VAS). | 161.36 pain intensity score*hr | Standard Deviation 86.627 |
| Cohort 4 | Mean Area Under the Curve (AUC) of the Visual Analogue Scale (VAS). | 126.59 pain intensity score*hr | Standard Deviation 118.431 |
Secondary
Maximum Concentration (Cmax)
Time frame: 72 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 and Cohort 2 (Pooled) | Maximum Concentration (Cmax) | Bupivacaine | 566 ng/mL | Standard Deviation 273 |
| Cohort 1 and Cohort 2 (Pooled) | Maximum Concentration (Cmax) | Meloxicam | 238 ng/mL | Standard Deviation 96.8 |
| Cohort 3: Group A | Maximum Concentration (Cmax) | Meloxicam | 247 ng/mL | Standard Deviation 89 |
| Cohort 3: Group A | Maximum Concentration (Cmax) | Bupivacaine | 534 ng/mL | Standard Deviation 175 |
| Cohort 3: Group B | Maximum Concentration (Cmax) | Bupivacaine | 742 ng/mL | Standard Deviation 268 |
| Cohort 3: Group B | Maximum Concentration (Cmax) | Meloxicam | 251 ng/mL | Standard Deviation 104 |
| Cohort 4 | Maximum Concentration (Cmax) | Bupivacaine | 851 ng/mL | Standard Deviation 288 |
| Cohort 4 | Maximum Concentration (Cmax) | Meloxicam | 385 ng/mL | Standard Deviation 161 |
Secondary
Mean AUC of the NRS of Pain Intensity at Rest (NRS-R).
Pain intensity scores are assessed using an 11-point Numeric Rating Scale (NRS) (0-10) where 0 represents no pain and 10 represents worst pain. NRS scores are measured at rest.
Time frame: 72 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 and Cohort 2 (Pooled) | Mean AUC of the NRS of Pain Intensity at Rest (NRS-R). | 309.89 pain intensity score*hr | Standard Deviation 155.289 |
| Cohort 3: Group A | Mean AUC of the NRS of Pain Intensity at Rest (NRS-R). | 355.20 pain intensity score*hr | Standard Deviation 161.377 |
| Cohort 3: Group B | Mean AUC of the NRS of Pain Intensity at Rest (NRS-R). | 311.00 pain intensity score*hr | Standard Deviation 136.714 |
| Cohort 4 | Mean AUC of the NRS of Pain Intensity at Rest (NRS-R). | 245.00 pain intensity score*hr | Standard Deviation 200.369 |
Secondary
Mean AUC of VAS Scores.
The Visual Analog Scale (VAS) consists of a straight 10-cm line that represents pain ranging from no pain to pain as bad as it could be. Subjects were asked to mark their current pain level on the line.
Time frame: 72 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 and Cohort 2 (Pooled) | Mean AUC of VAS Scores. | 277.03 pain intensity score*hr | Standard Deviation 164.004 |
| Cohort 3: Group A | Mean AUC of VAS Scores. | 319.81 pain intensity score*hr | Standard Deviation 158.746 |
| Cohort 3: Group B | Mean AUC of VAS Scores. | 276.87 pain intensity score*hr | Standard Deviation 146.578 |
| Cohort 4 | Mean AUC of VAS Scores. | 216.18 pain intensity score*hr | Standard Deviation 206.164 |
Secondary
Mean Overall Benefit of Analgesia Score (OBAS).
Subjects were questioned about their overall benefit of analgesia. Overall benefit of analgesia score (OBAS) assesses current pain at rest, vomiting, itching, sweating, freezing, dizziness, and overall satisfaction with postoperative pain during the previous 24 hours. To calculate the OBAS score, each of the subscale scores (0=minimum; 4=maximum) are summed for a combined OBAS score. Possible scores could range from 0 to 28 with a lower score indicating greater benefit.
Time frame: 24 hours, 48 hours, 72 hours, Day 11
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 and Cohort 2 (Pooled) | Mean Overall Benefit of Analgesia Score (OBAS). | 24 Hours | 6.5 Scores on a scale | Standard Deviation 2.75 |
| Cohort 1 and Cohort 2 (Pooled) | Mean Overall Benefit of Analgesia Score (OBAS). | 48 Hours | 5.7 Scores on a scale | Standard Deviation 2.76 |
| Cohort 1 and Cohort 2 (Pooled) | Mean Overall Benefit of Analgesia Score (OBAS). | 72 Hours | 5.1 Scores on a scale | Standard Deviation 2.46 |
| Cohort 1 and Cohort 2 (Pooled) | Mean Overall Benefit of Analgesia Score (OBAS). | Day 11 | 5.0 Scores on a scale | Standard Deviation 2.43 |
| Cohort 3: Group A | Mean Overall Benefit of Analgesia Score (OBAS). | 48 Hours | 4.9 Scores on a scale | Standard Deviation 1.44 |
| Cohort 3: Group A | Mean Overall Benefit of Analgesia Score (OBAS). | 72 Hours | 4.1 Scores on a scale | Standard Deviation 1.77 |
| Cohort 3: Group A | Mean Overall Benefit of Analgesia Score (OBAS). | Day 11 | 5.2 Scores on a scale | Standard Deviation 2.08 |
| Cohort 3: Group A | Mean Overall Benefit of Analgesia Score (OBAS). | 24 Hours | 7.4 Scores on a scale | Standard Deviation 6.36 |
| Cohort 3: Group B | Mean Overall Benefit of Analgesia Score (OBAS). | 72 Hours | 4.9 Scores on a scale | Standard Deviation 1.88 |
| Cohort 3: Group B | Mean Overall Benefit of Analgesia Score (OBAS). | 48 Hours | 5.9 Scores on a scale | Standard Deviation 2.89 |
| Cohort 3: Group B | Mean Overall Benefit of Analgesia Score (OBAS). | Day 11 | 4.9 Scores on a scale | Standard Deviation 2.08 |
| Cohort 3: Group B | Mean Overall Benefit of Analgesia Score (OBAS). | 24 Hours | 7.6 Scores on a scale | Standard Deviation 3.24 |
| Cohort 4 | Mean Overall Benefit of Analgesia Score (OBAS). | Day 11 | 4.9 Scores on a scale | Standard Deviation 2.07 |
| Cohort 4 | Mean Overall Benefit of Analgesia Score (OBAS). | 48 Hours | 5.3 Scores on a scale | Standard Deviation 2.57 |
| Cohort 4 | Mean Overall Benefit of Analgesia Score (OBAS). | 24 Hours | 5.9 Scores on a scale | Standard Deviation 3.45 |
| Cohort 4 | Mean Overall Benefit of Analgesia Score (OBAS). | 72 Hours | 4.8 Scores on a scale | Standard Deviation 2.29 |
Secondary
Mean Total Postoperative Opioid Consumption (in IV Morphine Milligram Equivalents [MME]).
Time frame: 72 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 and Cohort 2 (Pooled) | Mean Total Postoperative Opioid Consumption (in IV Morphine Milligram Equivalents [MME]). | 26.40 MME, morphine milligram equivalency | Standard Deviation 23.229 |
| Cohort 3: Group A | Mean Total Postoperative Opioid Consumption (in IV Morphine Milligram Equivalents [MME]). | 31.50 MME, morphine milligram equivalency | Standard Deviation 24.907 |
| Cohort 3: Group B | Mean Total Postoperative Opioid Consumption (in IV Morphine Milligram Equivalents [MME]). | 23.40 MME, morphine milligram equivalency | Standard Deviation 14.484 |
| Cohort 4 | Mean Total Postoperative Opioid Consumption (in IV Morphine Milligram Equivalents [MME]). | 17.62 MME, morphine milligram equivalency | Standard Deviation 22.167 |
Secondary
Mean Total TSQM-9 Score
The Treatment Satisfaction Questionnaire for Medication (TSQM-9) contains 9 items assessing Effectiveness, Convenience, and Global Satisfaction domains. Responses to items are rated on a 5-point or 7-point rating scale. Scores for each domain are computed by adding the TSQM items in each domain and then transforming the values in to a composite score ranging from 0 to 100, with higher scores representing higher satisfaction.
Time frame: 72 hours through Day 11
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 and Cohort 2 (Pooled) | Mean Total TSQM-9 Score | Global Satisfaction Domain - 72 Hours | 86.9 Scores on a scale | Standard Deviation 15.53 |
| Cohort 1 and Cohort 2 (Pooled) | Mean Total TSQM-9 Score | Effectiveness Doman - 72 Hours | 86.4 Scores on a scale | Standard Deviation 18.09 |
| Cohort 1 and Cohort 2 (Pooled) | Mean Total TSQM-9 Score | Convenience Domain - 72 Hours | 90.1 Scores on a scale | Standard Deviation 12.03 |
| Cohort 1 and Cohort 2 (Pooled) | Mean Total TSQM-9 Score | Global Satisfaction Domain - Day 11 | 78.0 Scores on a scale | Standard Deviation 22.39 |
| Cohort 1 and Cohort 2 (Pooled) | Mean Total TSQM-9 Score | Effectiveness Doman - Day 11 | 76.3 Scores on a scale | Standard Deviation 21.18 |
| Cohort 1 and Cohort 2 (Pooled) | Mean Total TSQM-9 Score | Convenience Domain - Day 11 | 90.1 Scores on a scale | Standard Deviation 12.03 |
| Cohort 3: Group A | Mean Total TSQM-9 Score | Convenience Domain - Day 11 | 86.9 Scores on a scale | Standard Deviation 15.5 |
| Cohort 3: Group A | Mean Total TSQM-9 Score | Global Satisfaction Domain - Day 11 | 74.5 Scores on a scale | Standard Deviation 27.27 |
| Cohort 3: Group A | Mean Total TSQM-9 Score | Global Satisfaction Domain - 72 Hours | 77.0 Scores on a scale | Standard Deviation 22.62 |
| Cohort 3: Group A | Mean Total TSQM-9 Score | Convenience Domain - 72 Hours | 84.5 Scores on a scale | Standard Deviation 17.18 |
| Cohort 3: Group A | Mean Total TSQM-9 Score | Effectiveness Doman - 72 Hours | 80.2 Scores on a scale | Standard Deviation 20.52 |
| Cohort 3: Group A | Mean Total TSQM-9 Score | Effectiveness Doman - Day 11 | 69.4 Scores on a scale | Standard Deviation 29.13 |
| Cohort 3: Group B | Mean Total TSQM-9 Score | Effectiveness Doman - 72 Hours | 84.0 Scores on a scale | Standard Deviation 14.61 |
| Cohort 3: Group B | Mean Total TSQM-9 Score | Convenience Domain - 72 Hours | 93.1 Scores on a scale | Standard Deviation 13.07 |
| Cohort 3: Group B | Mean Total TSQM-9 Score | Global Satisfaction Domain - Day 11 | 72.8 Scores on a scale | Standard Deviation 21.22 |
| Cohort 3: Group B | Mean Total TSQM-9 Score | Convenience Domain - Day 11 | 80.9 Scores on a scale | Standard Deviation 15.31 |
| Cohort 3: Group B | Mean Total TSQM-9 Score | Effectiveness Doman - Day 11 | 69.4 Scores on a scale | Standard Deviation 29.13 |
| Cohort 3: Group B | Mean Total TSQM-9 Score | Global Satisfaction Domain - 72 Hours | 89.3 Scores on a scale | Standard Deviation 14.75 |
| Cohort 4 | Mean Total TSQM-9 Score | Effectiveness Doman - Day 11 | 67.0 Scores on a scale | Standard Deviation 24.8 |
| Cohort 4 | Mean Total TSQM-9 Score | Convenience Domain - Day 11 | 90.6 Scores on a scale | Standard Deviation 12.24 |
| Cohort 4 | Mean Total TSQM-9 Score | Effectiveness Doman - 72 Hours | 81.9 Scores on a scale | Standard Deviation 15.39 |
| Cohort 4 | Mean Total TSQM-9 Score | Global Satisfaction Domain - Day 11 | 82.9 Scores on a scale | Standard Deviation 18.16 |
| Cohort 4 | Mean Total TSQM-9 Score | Global Satisfaction Domain - 72 Hours | 86.8 Scores on a scale | Standard Deviation 13.57 |
| Cohort 4 | Mean Total TSQM-9 Score | Convenience Domain - 72 Hours | 86.9 Scores on a scale | Standard Deviation 16.45 |
Secondary
Median Time to First Ambulation Postsurgery.
Time frame: 72 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 and Cohort 2 (Pooled) | Median Time to First Ambulation Postsurgery. | 20.66 Hours |
| Cohort 3: Group A | Median Time to First Ambulation Postsurgery. | 23.20 Hours |
| Cohort 3: Group B | Median Time to First Ambulation Postsurgery. | 26.72 Hours |
| Cohort 4 | Median Time to First Ambulation Postsurgery. | 20.58 Hours |
Secondary
Median Time to First Opioid Rescue Medication.
Time frame: Through 72 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 and Cohort 2 (Pooled) | Median Time to First Opioid Rescue Medication. | 6.12 Hours |
| Cohort 3: Group A | Median Time to First Opioid Rescue Medication. | 5.63 Hours |
| Cohort 3: Group B | Median Time to First Opioid Rescue Medication. | 9.96 Hours |
| Cohort 4 | Median Time to First Opioid Rescue Medication. | 12.76 Hours |
Secondary
Percentage of Subjects Achieving a Score of Good or Better (>1) Pain Control Based on Patient Global Assessment (PGA).
Patient's Global Assessment (PGA) of pain control is a 4-point scale in which subjects rate how well their pain has been controlled (0 = Poor; 1 = Fair; 2 = Good; 3 = Excellent).
Time frame: 24 hours, 48 hours, 72 hours, Day 11
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Achieving a Score of Good or Better (>1) Pain Control Based on Patient Global Assessment (PGA). | 24 Hours | 60 Participants |
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Achieving a Score of Good or Better (>1) Pain Control Based on Patient Global Assessment (PGA). | 48 Hours | 61 Participants |
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Achieving a Score of Good or Better (>1) Pain Control Based on Patient Global Assessment (PGA). | 72 Hours | 66 Participants |
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Achieving a Score of Good or Better (>1) Pain Control Based on Patient Global Assessment (PGA). | Day 11 | 50 Participants |
| Cohort 3: Group A | Percentage of Subjects Achieving a Score of Good or Better (>1) Pain Control Based on Patient Global Assessment (PGA). | 48 Hours | 11 Participants |
| Cohort 3: Group A | Percentage of Subjects Achieving a Score of Good or Better (>1) Pain Control Based on Patient Global Assessment (PGA). | 72 Hours | 12 Participants |
| Cohort 3: Group A | Percentage of Subjects Achieving a Score of Good or Better (>1) Pain Control Based on Patient Global Assessment (PGA). | Day 11 | 11 Participants |
| Cohort 3: Group A | Percentage of Subjects Achieving a Score of Good or Better (>1) Pain Control Based on Patient Global Assessment (PGA). | 24 Hours | 10 Participants |
| Cohort 3: Group B | Percentage of Subjects Achieving a Score of Good or Better (>1) Pain Control Based on Patient Global Assessment (PGA). | 72 Hours | 15 Participants |
| Cohort 3: Group B | Percentage of Subjects Achieving a Score of Good or Better (>1) Pain Control Based on Patient Global Assessment (PGA). | 48 Hours | 14 Participants |
| Cohort 3: Group B | Percentage of Subjects Achieving a Score of Good or Better (>1) Pain Control Based on Patient Global Assessment (PGA). | Day 11 | 11 Participants |
| Cohort 3: Group B | Percentage of Subjects Achieving a Score of Good or Better (>1) Pain Control Based on Patient Global Assessment (PGA). | 24 Hours | 14 Participants |
| Cohort 4 | Percentage of Subjects Achieving a Score of Good or Better (>1) Pain Control Based on Patient Global Assessment (PGA). | Day 11 | 15 Participants |
| Cohort 4 | Percentage of Subjects Achieving a Score of Good or Better (>1) Pain Control Based on Patient Global Assessment (PGA). | 48 Hours | 16 Participants |
| Cohort 4 | Percentage of Subjects Achieving a Score of Good or Better (>1) Pain Control Based on Patient Global Assessment (PGA). | 24 Hours | 16 Participants |
| Cohort 4 | Percentage of Subjects Achieving a Score of Good or Better (>1) Pain Control Based on Patient Global Assessment (PGA). | 72 Hours | 18 Participants |
Secondary
Percentage of Subjects Unable to Participate in Each Rehabilitation Session Because of Pain.
Time frame: 72 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Unable to Participate in Each Rehabilitation Session Because of Pain. | 23 Participants |
| Cohort 3: Group A | Percentage of Subjects Unable to Participate in Each Rehabilitation Session Because of Pain. | 1 Participants |
| Cohort 3: Group B | Percentage of Subjects Unable to Participate in Each Rehabilitation Session Because of Pain. | 2 Participants |
| Cohort 4 | Percentage of Subjects Unable to Participate in Each Rehabilitation Session Because of Pain. | 3 Participants |
Secondary
Percentage of Subjects Who Are Discharged Home vs to a Skilled Nursing Facility.
Number Analyzed represents Subjects who were discharged home.
Time frame: 72 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Who Are Discharged Home vs to a Skilled Nursing Facility. | 61 Participants |
| Cohort 3: Group A | Percentage of Subjects Who Are Discharged Home vs to a Skilled Nursing Facility. | 10 Participants |
| Cohort 3: Group B | Percentage of Subjects Who Are Discharged Home vs to a Skilled Nursing Facility. | 16 Participants |
| Cohort 4 | Percentage of Subjects Who Are Discharged Home vs to a Skilled Nursing Facility. | 20 Participants |
Secondary
Percentage of Subjects Who Are Opioid-free
Time frame: 72 Hours to Day 11
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Who Are Opioid-free | 25 participants |
| Cohort 3: Group A | Percentage of Subjects Who Are Opioid-free | 4 participants |
| Cohort 3: Group B | Percentage of Subjects Who Are Opioid-free | 3 participants |
| Cohort 4 | Percentage of Subjects Who Are Opioid-free | 10 participants |
Secondary
Percentage of Subjects Who Are Opioid-free Through 72 Hours Who Remain Opioid-free Through Day 11.
Time frame: 72 hours through Day 11
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Who Are Opioid-free Through 72 Hours Who Remain Opioid-free Through Day 11. | 9 Participants |
| Cohort 3: Group A | Percentage of Subjects Who Are Opioid-free Through 72 Hours Who Remain Opioid-free Through Day 11. | 1 Participants |
| Cohort 3: Group B | Percentage of Subjects Who Are Opioid-free Through 72 Hours Who Remain Opioid-free Through Day 11. | 0 Participants |
| Cohort 4 | Percentage of Subjects Who Are Opioid-free Through 72 Hours Who Remain Opioid-free Through Day 11. | 5 Participants |
Secondary
Percentage of Subjects Who do Not Receive an Opioid Prescription at Discharge.
Time frame: 72 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Who do Not Receive an Opioid Prescription at Discharge. | 41 Participants |
| Cohort 3: Group A | Percentage of Subjects Who do Not Receive an Opioid Prescription at Discharge. | 8 Participants |
| Cohort 3: Group B | Percentage of Subjects Who do Not Receive an Opioid Prescription at Discharge. | 12 Participants |
| Cohort 4 | Percentage of Subjects Who do Not Receive an Opioid Prescription at Discharge. | 13 Participants |
Secondary
Percentage of Subjects Who do Not Receive an Opioid Prescription Between Discharge and the Day 11 Visit.
Time frame: 72 hours through Day 11
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Who do Not Receive an Opioid Prescription Between Discharge and the Day 11 Visit. | 44 Participants |
| Cohort 3: Group A | Percentage of Subjects Who do Not Receive an Opioid Prescription Between Discharge and the Day 11 Visit. | 8 Participants |
| Cohort 3: Group B | Percentage of Subjects Who do Not Receive an Opioid Prescription Between Discharge and the Day 11 Visit. | 8 Participants |
| Cohort 4 | Percentage of Subjects Who do Not Receive an Opioid Prescription Between Discharge and the Day 11 Visit. | 17 Participants |
Secondary
Percentage of Subjects Who First Achieve an MPADSS Score ≥9.
Subjects were assessed for readiness for discharge using the Modified Post-Anesthesia Discharge Scoring System (MPADSS) that assesses 5 clinical variables: vital signs, ambulation, nausea/vomiting, pain, and surgical bleeding, each on a 3-point scale of 0, 1, or 2 with 0 being the worst score and 2 being the best score. Subjects with an MPADSS score of 9 or 10 were considered ready for discharge.
Time frame: 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24, hours, 36 hours, 48 hours, 60 hours, 72 hours
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 2 Hours | 15 Participants |
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 4 Hours | 16 Participants |
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 6 Hours | 21 Participants |
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 8 Hours | 29 Participants |
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 12 Hours | 38 Participants |
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 24 Hours | 45 Participants |
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 36 Hours | 52 Participants |
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 48 Hours | 57 Participants |
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 72 Hours | 59 Participants |
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 60 Hours | 57 Participants |
| Cohort 3: Group A | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 8 Hours | 6 Participants |
| Cohort 3: Group A | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 12 Hours | 7 Participants |
| Cohort 3: Group A | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 24 Hours | 8 Participants |
| Cohort 3: Group A | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 2 Hours | 2 Participants |
| Cohort 3: Group A | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 36 Hours | 12 Participants |
| Cohort 3: Group A | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 48 Hours | 12 Participants |
| Cohort 3: Group A | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 60 Hours | 12 Participants |
| Cohort 3: Group A | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 4 Hours | 3 Participants |
| Cohort 3: Group A | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 6 Hours | 6 Participants |
| Cohort 3: Group A | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 72 Hours | 13 Participants |
| Cohort 3: Group B | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 24 Hours | 11 Participants |
| Cohort 3: Group B | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 4 Hours | 2 Participants |
| Cohort 3: Group B | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 36 Hours | 13 Participants |
| Cohort 3: Group B | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 2 Hours | 2 Participants |
| Cohort 3: Group B | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 48 Hours | 13 Participants |
| Cohort 3: Group B | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 60 Hours | 15 Participants |
| Cohort 3: Group B | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 8 Hours | 8 Participants |
| Cohort 3: Group B | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 72 Hours | 15 Participants |
| Cohort 3: Group B | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 12 Hours | 9 Participants |
| Cohort 3: Group B | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 6 Hours | 5 Participants |
| Cohort 4 | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 24 Hours | 15 Participants |
| Cohort 4 | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 12 Hours | 8 Participants |
| Cohort 4 | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 4 Hours | 3 Participants |
| Cohort 4 | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 8 Hours | 8 Participants |
| Cohort 4 | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 36 Hours | 18 Participants |
| Cohort 4 | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 72 Hours | 19 Participants |
| Cohort 4 | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 2 Hours | 0 Participants |
| Cohort 4 | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 60 Hours | 19 Participants |
| Cohort 4 | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 48 Hours | 19 Participants |
| Cohort 4 | Percentage of Subjects Who First Achieve an MPADSS Score ≥9. | Through 6 Hours | 7 Participants |
Secondary
Percentage of Subjects With Severe Pain.
Severe Pain defined as a VAS score ≥7.5 cm.
Time frame: 24 hours, 48 hours, 72 hours
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects With Severe Pain. | 72 Hours | 23 Participants |
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects With Severe Pain. | 24 Hours | 26 Participants |
| Cohort 1 and Cohort 2 (Pooled) | Percentage of Subjects With Severe Pain. | 48 Hours | 29 Participants |
| Cohort 3: Group A | Percentage of Subjects With Severe Pain. | 72 Hours | 5 Participants |
| Cohort 3: Group A | Percentage of Subjects With Severe Pain. | 48 Hours | 5 Participants |
| Cohort 3: Group A | Percentage of Subjects With Severe Pain. | 24 Hours | 4 Participants |
| Cohort 3: Group B | Percentage of Subjects With Severe Pain. | 24 Hours | 5 Participants |
| Cohort 3: Group B | Percentage of Subjects With Severe Pain. | 48 Hours | 5 Participants |
| Cohort 3: Group B | Percentage of Subjects With Severe Pain. | 72 Hours | 5 Participants |
| Cohort 4 | Percentage of Subjects With Severe Pain. | 72 Hours | 7 Participants |
| Cohort 4 | Percentage of Subjects With Severe Pain. | 24 Hours | 6 Participants |
| Cohort 4 | Percentage of Subjects With Severe Pain. | 48 Hours | 6 Participants |
Secondary
Time of Occurrence of Maximum Concentration (Tmax)
Time frame: 72 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 and Cohort 2 (Pooled) | Time of Occurrence of Maximum Concentration (Tmax) | Bupivacaine | 21.05 hours |
| Cohort 1 and Cohort 2 (Pooled) | Time of Occurrence of Maximum Concentration (Tmax) | Meloxicam | 47.13 hours |
| Cohort 3: Group A | Time of Occurrence of Maximum Concentration (Tmax) | Meloxicam | 58.58 hours |
| Cohort 3: Group A | Time of Occurrence of Maximum Concentration (Tmax) | Bupivacaine | 20.54 hours |
| Cohort 3: Group B | Time of Occurrence of Maximum Concentration (Tmax) | Bupivacaine | 20.14 hours |
| Cohort 3: Group B | Time of Occurrence of Maximum Concentration (Tmax) | Meloxicam | 37.17 hours |
| Cohort 4 | Time of Occurrence of Maximum Concentration (Tmax) | Bupivacaine | 22.48 hours |
| Cohort 4 | Time of Occurrence of Maximum Concentration (Tmax) | Meloxicam | 48.58 hours |