HTX-011 Administration Study in Planned Caesarean Section Procedure

Study Overview
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Brief Summary
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This is a Phase 2, open-label study to evaluate the PK and safety of HTX-011 in women undergoing a planned C-section.

Official Title
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A Phase 2 Open-Label Study of the Pharmacokinetics (PK) and Safety of HTX-011 Administered Postpartum to Women Undergoing a Planned Caesarean Section

Conditions
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Analgesia

Intervention / Treatment
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* Drug: HTX-011
* Drug: HTX-011
* Device: Luer Lock Applicator
* Drug: Ibuprofen
* Drug: Acetaminophen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is expected, at the time of Screening visit, to deliver a single neonate. Is scheduled to undergo a planned C-section surgery with a low transverse skin incision (eg, Pfannenstiel). Has American Society of Anesthesiologists (ASA) Physical Status of I, II, or III. Agrees to practice abstinence or use double-barrier contraception in the event of sexual activity and commits to the use of an acceptable form of birth control for 30 days after HTX-011 administration. Agrees to refrain from the use of breast milk from this pregnancy in any manner. Exclusion Criteria: Has planned to breastfeed her neonate at any time during the 28-day period after HTX-011 administration. Has had a prior full-term pregnancy with unsuccessful breast milk expression. Has a planned concurrent surgical procedure. Has a contraindication or a known or suspected history of hypersensitivity or clinically significant idiosyncratic reaction to required study medications. 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 been administered systemic steroids within 5 half-lives or 10 days prior to administration of study drug. Has initiated treatment with study medications within 1 month prior to study drug administration that can impact pain control. Has taken any NSAIDs within least 10 days prior to the scheduled surgery. Has current significant placental abnormality/complications including, but not limited to, placenta previa or placenta accreta. 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. Has uncontrolled anxiety, psychiatric, or neurological disorder. 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 a known or suspected history of drug abuse, a positive drug screen on the day of surgery, or a recent history of alcohol abuse. Previously participated in an HTX-011 study. Received an investigational product or device in a clinical trial within 30 days or within 5 elimination half-lives. Weight is <50 kg at the time of Screening visit. In the Investigator's judgment, subject is likely to have been morbidly obese prior to her pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group 1<br>A single dose of HTX-011 administered via instillation into the surgical site. | Drug: HTX-011<br>* 300 mg<br>* Other names: Cohort 1;Device: Luer Lock Applicator<br>* Applicator for instillation.<br>|
| Experimental: Treatment Group 2<br>A single dose of HTX-011 administered via instillation into the surgical site and a scheduled non-opioid multimodal analgesic (MMA) regimen. | Drug: HTX-011<br>* 400 mg<br>* Other names: Cohort 2;Device: Luer Lock Applicator<br>* Applicator for instillation.<br>Drug: Ibuprofen<br>* 400 mg<br>Drug: Acetaminophen<br>* 975 mg to 1 g<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) of bupivacaine, meloxicam, dimethyl sulfoxide (DMSO) and HTX-011 polymer |  | Day 1 to Day 16 for Cohort 1; Day 1 to Day 11 for Cohort 2 | 
| Time of maximum plasma concentration (Tmax) of bupivacaine, meloxicam, DMSO and HTX-011 polymer |  | Day 1 to Day 16 for Cohort 1; Day 1 to Day 11 for Cohort 2 | 
| Half life (t1/2) in plasma of bupivacaine, meloxicam, DMSO and HTX-011 polymer |  | Day 1 to Day 16 for Cohort 1; Day 1 to Day 11 for Cohort 2 | 
| Half life (t1/2) in milk of bupivacaine, meloxicam, DMSO and HTX-011 polymer |  | Day 1 to Day 16 for Cohort 1; Day 1 to Day 11 for Cohort 2 | 
| Amount of analyte excreted in breast milk over time (Ae) |  | Day 1 to Day 16 for Cohort 1; Day 1 to Day 11 for Cohort 2 | 
| Fraction of dose excreted in breast milk over time (Fe) |  | Day 1 to Day 16 for Cohort 1; Day 1 to Day 11 for Cohort 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean area under the curve of the NRS pain scores through 72 hours (AUC0-72). |  | 72 hours | 
| Incidence of treatment-emergent adverse events (TEAEs). |  | 28 Days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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postoperative pain, caesarean section, C-section