Bunions, Postoperative Pain
Conditions
Keywords
Analgesia, Bunionectomy
Brief summary
A Phase 2, Randomized, Controlled, Multicenter, Evaluation of the Efficacy and Safety of Locally Administered HTX-011 for Postoperative Analgesia Following Bunionectomy
Detailed description
This study includes multiple formulations for formulation selection of the fixed-combination product and for the factorial design assessment of the contribution of each component. HTX-011A is the second formulation studied (HTX-011-49). HTX-011B is the final formulation studied (HTX-011-56), which was also included in subsequent Phase 2b and Phase 3 studies. For the factorial design assessment, HTX-002, a bupivacaine-only formulation in the same HTX-011 proprietary polymer, and HTX-009, a meloxicam-only formulation in the same HTX-011 proprietary polymer, were evaluated.
Interventions
DRUGHTX-011A
HTX-011A (bupivacaine/meloxicam), via injection.
BIOLOGICALSaline Placebo
Saline placebo via injection.
DRUGHTX-011B
HTX-011B (bupivacaine/meloxicam), via injection or instillation.
DRUGHTX-002
HTX-002, via injection.
DRUGBupivacaine HCl
Bupivacaine HCI, via injection.
DRUGHTX-009
HTX-009, via injection.
Sponsors
Heron Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Be male or female 18 years of age or older 2. Female subjects are eligible only if all of the following apply: 1. Not pregnant (female subject of child bearing potential must have a negative serum pregnancy test at screening and negative urine pregnancy test before surgery) 2. Not lactating 3. Not planning to become pregnant while participating in the study 4. Be surgically sterile; or be at least two years post-menopausal; or have a monogamous partner who is surgically sterile; or be 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, transdermal, or combination oral contraceptive approved by the FDA for greater than 2 months prior to screening visits and commits to the use of an acceptable form of birth control for the duration of the study and for 30 days from completion of the study 3. Male subjects must be surgically sterile (biologically or surgically) or commit to the use of a reliable method of birth control for the duration of the study until at least 1 week after the administration of study medication 4. Be scheduled to undergo a primary unilateral first metatarsal bunionectomy repair, without collateral procedures, under regional anesthesia 5. Subject has not had a contralateral bunionectomy in the non-study foot in the past 3 months 6. Have the ability and be willing to comply with the study procedures. 7. Must be able to understand study procedures and give informed consent for the conduct for all study procedures, using an IRB approved consent form
Exclusion criteria
1. Unwilling to sign informed consent or not willing or able to complete all study procedures 2. Have a contraindication or be allergic to any medication to be used during the trial period 3. Have clinically significant cardiac abnormalities that, in the opinion of the investigator, would pose a health risk to the subject 4. Have American Society of Anesthesiologists (ASA) Physical Status classification system category ≥4 5. Have clinically significant renal or hepatic abnormalities: for example, AST or ALT \> 3x ULN, creatinine \> 2x ULN 6. Have another pre-existing painful condition that may confound pain assessments 7. Have another surgery planned within 30 days of procedure 8. Have a known or suspected history of alcohol or drug abuse, or a positive drug screen 9. Currently taking analgesics for a chronically painful condition, or has taken long acting opioids within 3 days of surgery, or taken any opioids within 24 hours of scheduled surgery for this study 10. Subjects with documented sleep apnea or are on home continuous positive airway pressure (CPAP) 11. Subjects who are receiving oxygen therapy at the time of screening 12. Have participated in a clinical trial within 30 days of planned surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Summed Pain Intensity (SPI) Score Over 24 Hours | 0-24 hours | The SPI is derived by summing the pain intensity score weighted by the scheduled time duration. SPI0-24 will be calculated by summing the Pain intensity (PI) score at the relevant time points weighted by the scheduled time duration since the prior PI assessment as follows: SPI0-24= PI1+PI2+2\*PI4+2\*PI6+2\*PI8+2\*PI10+2\*PI12+2\*PI14+4\*PI18+6\*PI24. Min = 0 (if PI=0 at every time) and Max = 240 (if PI=10 at every time). |
Countries
United States
Participant flow
Pre-assignment details
Study HTX-011-208 included multiple study parts, various study drugs, formulations, and administration techniques. It was pre-specified in the SAP to pool different doses of the same study drug within study parts for Participant Flow, Baseline Characteristics, and AEs. We pooled different doses of the same study drug within study parts for Participant Flow, Baseline Characteristics, and AEs. However for Outcome Measures, different doses of study drugs were presented separately.
Participants by arm
| Arm | Count |
|---|---|
| HTX-011A HTX-011A (bupivacaine/meloxicam), 200 mg/6 mg via injection. | 33 |
| HTX-011B HTX-011B (bupivacaine/meloxicam), 30-200 mg/0.9-6 mg via injection or instillation. | 174 |
| Bupivacaine HCI Bupivacaine HCI, 50 mg via injection. | 25 |
| Saline Placebo Saline placebo via injection. | 104 |
| HTX-002 HTX-002, 60-200 mg via injection. | 64 |
| HTX-009 HTX-009, 3.6 mg via injection. | 30 |
| Total | 430 |
Baseline characteristics
| Characteristic | HTX-011A | HTX-011B | Bupivacaine HCI | Saline Placebo | HTX-002 | HTX-009 | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 25 Participants | 2 Participants | 18 Participants | 8 Participants | 4 Participants | 62 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 149 Participants | 23 Participants | 86 Participants | 56 Participants | 26 Participants | 368 Participants |
| Age, Continuous | 49.7 Years STANDARD_DEVIATION 13.86 | 50.4 Years STANDARD_DEVIATION 13.79 | 52.7 Years STANDARD_DEVIATION 11.81 | 50.0 Years STANDARD_DEVIATION 13.46 | 50.2 Years STANDARD_DEVIATION 12.51 | 49.9 Years STANDARD_DEVIATION 13.41 | 50.3 Years STANDARD_DEVIATION 13.34 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 50 Participants | 5 Participants | 28 Participants | 26 Participants | 10 Participants | 128 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 124 Participants | 20 Participants | 76 Participants | 38 Participants | 20 Participants | 302 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 33 participants | 174 participants | 25 participants | 104 participants | 64 participants | 30 participants | 430 participants |
| Sex: Female, Male Female | 27 Participants | 148 Participants | 22 Participants | 91 Participants | 57 Participants | 27 Participants | 372 Participants |
| Sex: Female, Male Male | 6 Participants | 26 Participants | 3 Participants | 13 Participants | 7 Participants | 3 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 174 | 0 / 25 | 0 / 104 | 0 / 64 | 0 / 30 |
| other Total, other adverse events | 20 / 33 | 113 / 174 | 19 / 25 | 70 / 104 | 43 / 64 | 20 / 30 |
| serious Total, serious adverse events | 1 / 33 | 1 / 174 | 0 / 25 | 0 / 104 | 0 / 64 | 2 / 30 |
Outcome results
Primary
Mean Summed Pain Intensity (SPI) Score Over 24 Hours
The SPI is derived by summing the pain intensity score weighted by the scheduled time duration. SPI0-24 will be calculated by summing the Pain intensity (PI) score at the relevant time points weighted by the scheduled time duration since the prior PI assessment as follows: SPI0-24= PI1+PI2+2\*PI4+2\*PI6+2\*PI8+2\*PI10+2\*PI12+2\*PI14+4\*PI18+6\*PI24. Min = 0 (if PI=0 at every time) and Max = 240 (if PI=10 at every time).
Time frame: 0-24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HTX-011A: 200 mg | Mean Summed Pain Intensity (SPI) Score Over 24 Hours | 69.16 Units on a scale | Standard Deviation 43.092 |
| HTX-011B: 30 mg | Mean Summed Pain Intensity (SPI) Score Over 24 Hours | 96.83 Units on a scale | Standard Deviation 50.151 |
| HTX-011B: 60 mg | Mean Summed Pain Intensity (SPI) Score Over 24 Hours | 83.38 Units on a scale | Standard Deviation 46.226 |
| HTX-011B: 120 mg | Mean Summed Pain Intensity (SPI) Score Over 24 Hours | 85.70 Units on a scale | Standard Deviation 40.716 |
| HTX-011B: 200 mg | Mean Summed Pain Intensity (SPI) Score Over 24 Hours | 49.23 Units on a scale | Standard Deviation 40.781 |
| Bupivacaine HCI: 50 mg | Mean Summed Pain Intensity (SPI) Score Over 24 Hours | 118.16 Units on a scale | Standard Deviation 50.634 |
| Saline Placebo | Mean Summed Pain Intensity (SPI) Score Over 24 Hours | 126.46 Units on a scale | Standard Deviation 47.785 |
| HTX-002, 60 mg | Mean Summed Pain Intensity (SPI) Score Over 24 Hours | 112.00 Units on a scale | Standard Deviation 37.239 |
| HTX-002, 120 mg | Mean Summed Pain Intensity (SPI) Score Over 24 Hours | 129.97 Units on a scale | Standard Deviation 45.897 |
| HTX-002, 200 mg | Mean Summed Pain Intensity (SPI) Score Over 24 Hours | 107.82 Units on a scale | Standard Deviation 60.547 |
| HTX-009 | Mean Summed Pain Intensity (SPI) Score Over 24 Hours | 127.83 Units on a scale | Standard Deviation 49.196 |