Evaluation of the Efficacy and Safety of Locally Administered HTX-011 for Postoperative Analgesia Following Bunionectomy

Study Overview
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Brief Summary
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A Phase 2, Randomized, Controlled, Multicenter, Evaluation of the Efficacy and Safety of Locally Administered HTX-011 for Postoperative Analgesia Following Bunionectomy

Detailed Description
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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.

Official Title
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A Phase 2, Randomized, Controlled, Multicenter, Evaluation of the Efficacy and Safety of Locally Administered HTX-011, HTX-002, or HTX-009 for Postoperative Analgesia Following Bunionectomy

Conditions
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Postoperative Pain, Bunions

Intervention / Treatment
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* Drug: HTX-011A
* Biological: Saline Placebo
* Drug: HTX-011B
* Drug: HTX-002
* Drug: Bupivacaine HCl
* Drug: HTX-009


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be male or female 18 years of age or older Female subjects are eligible only if all of the following apply: Not pregnant (female subject of child bearing potential must have a negative serum pregnancy test at screening and negative urine pregnancy test before surgery) Not lactating Not planning to become pregnant while participating in the study 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 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 Be scheduled to undergo a primary unilateral first metatarsal bunionectomy repair, without collateral procedures, under regional anesthesia Subject has not had a contralateral bunionectomy in the non-study foot in the past 3 months Have the ability and be willing to comply with the study procedures. 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: Unwilling to sign informed consent or not willing or able to complete all study procedures Have a contraindication or be allergic to any medication to be used during the trial period Have clinically significant cardiac abnormalities that, in the opinion of the investigator, would pose a health risk to the subject Have American Society of Anesthesiologists (ASA) Physical Status classification system category ≥4 Have clinically significant renal or hepatic abnormalities: for example, AST or ALT > 3x ULN, creatinine > 2x ULN Have another pre-existing painful condition that may confound pain assessments Have another surgery planned within 30 days of procedure Have a known or suspected history of alcohol or drug abuse, or a positive drug screen 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 Subjects with documented sleep apnea or are on home continuous positive airway pressure (CPAP) Subjects who are receiving oxygen therapy at the time of screening Have participated in a clinical trial within 30 days of planned surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HTX-011A: 200 mg<br>HTX-011A (bupivacaine/meloxicam), 200 mg/6 mg via injection. | Drug: HTX-011A<br>* HTX-011A (bupivacaine/meloxicam), via injection.<br>|
| Experimental: HTX-011B: 30 mg<br>HTX 011B (bupivacaine/meloxicam), 30 mg/0.9 mg via injection. | Drug: HTX-011B<br>* HTX-011B (bupivacaine/meloxicam), via injection or instillation.<br>|
| Experimental: HTX-011B : 60 mg<br>HTX-011B (bupivacaine/meloxicam) 60 mg/1.8 mg via injection or instillation. | Drug: HTX-011B<br>* HTX-011B (bupivacaine/meloxicam), via injection or instillation.<br>|
| Experimental: HTX-011B: 120 mg<br>HTX- 011B (bupivacaine/meloxicam), 120 mg/3.6 mg via injection or instillation. | Drug: HTX-011B<br>* HTX-011B (bupivacaine/meloxicam), via injection or instillation.<br>|
| Experimental: HTX-011B: 200 mg<br>HTX- 011B (bupivacaine/meloxicam), 200 mg/6 mg via injection. | Drug: HTX-011B<br>* HTX-011B (bupivacaine/meloxicam), via injection or instillation.<br>|
| Active Comparator: Bupivacaine HCI<br>Bupivacaine HCI, 50 mg via injection. | Drug: Bupivacaine HCl<br>* Bupivacaine HCI, via injection.<br>|
| Active Comparator: Saline Placebo<br>Saline placebo via injection. | Biological: Saline Placebo<br>* Saline placebo via injection.<br>|
| Experimental: HTX-002, 60 mg<br>HTX- 002, 60 mg via injection. | Drug: HTX-002<br>* HTX-002, via injection.<br>|
| Experimental: HTX-002, 120 mg<br>HTX-002, 120 mg via injection. | Drug: HTX-002<br>* HTX-002, via injection.<br>|
| Experimental: HTX-002, 200 mg<br>HTX-002, 200 mg via injection. | Drug: HTX-002<br>* HTX-002, via injection.<br>|
| Experimental: HTX-009<br>HTX-009, 3.6 mg via injection. | Drug: HTX-009<br>* HTX-009, via injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 0-24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Analgesia, Bunionectomy