Sciatic nerve block with extended-release bupivacaine (ALX006) for bunion surgery

A Phase 2, Randomized, Double-blind, Active-controlled, Dose-escalation Study to Evaluate the Safety, Pharmacokinetics, Efficacy and Pharmacodynamics of ALX006 for Postsurgical Pain Management When Administered as a Sciatic (in the Popliteal Fossa) Nerve Block in Subjects Undergoing a Bunionectomy

This will test whether a single-dose extended-release bupivacaine (ALX006) given as a sciatic nerve block reduces pain after bunion surgery in adults.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Rebel Medicine Inc (Industry-sponsored)
• Locations: 1 site (Millcreek, Utah)
• Trial ID: NCT07574385 on ClinicalTrials.gov

What this trial studies

This is a phase 2, randomized, double-blind, active-controlled, dose-escalation study enrolling about 60 adults having primary unilateral bunionectomy. Participants receive a single sciatic (popliteal fossa) nerve block with one of three ALX006 doses (100 mg, 150 mg, 200 mg) or an active comparator (bupivacaine HCl 0.25%/50 mg) at a 3:1 randomization within each cohort. Safety, pharmacokinetics, analgesic efficacy, and pharmacodynamics are monitored, and an Independent Data Monitoring Committee governs dose escalation between cohorts. Outcomes include measures of postoperative pain control and opioid use following surgery.

Who should consider this trial

Good fit: Adults (≥18 years) scheduled for elective primary unilateral bunionectomy (Austin distal osteotomy), with ASA physical status 1–3 and BMI 18–40 kg/m2 who can consent and comply with study visits are the intended candidates.

Not a fit: Patients with allergy or contraindication to amide local anesthetics (including bupivacaine), those with other painful conditions likely to require additional opioid/NSAID treatment postoperatively, emergency or bilateral procedures, or those outside the ASA/BMI eligibility are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, ALX006 could provide longer-lasting regional pain relief after bunionectomy and reduce the need for opioid pain medicines.

How similar studies have performed: Similar approaches using extended-release bupivacaine formulations (for example, liposomal bupivacaine) have shown mixed but sometimes positive results for postoperative analgesia, so the approach has precedent but variable outcomes.

Eligibility criteria

Inclusion Criteria:

* Male or female, ages 18 or older at screening
* American Society of Anesthesiologists (ASA) physical status 1, 2, or 3 (see Appendix 5)
* Able to provide informed consent, adhere to the study schedule, and complete all study assessments
* Primary surgical indication is related to a bunion deformity (i.e., hallux valgus) and subject is scheduled to undergo a primary unilateral distal metaphyseal osteotomy procedure (i.e., Austin procedure)
* Indicated to undergo elective (i.e., not emergency) bunionectomy
* Body Mass Index (BMI) ≥18 and \<40 kg/m2

Exclusion Criteria:

* Allergy, hypersensitivity, intolerance, or contraindication to any of the study medications for which an alternative is not named in the protocol (e.g., amide-type local anesthetics, opioids, bupivacaine HCl, NSAIDs)
* Concurrent painful physical condition (e.g. arthritis, fibromyalgia, cancer) that may require analgesic treatment with NSAIDs or opioids in the post dosing period for pain that is not strictly related to the surgery and which, in the Investigator's opinion, may confound the post dosing assessments
* Inadequate sensory function of the foot/ankle as assessed by the Investigator
* History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past two (2) years
* Administration of an investigational drug within thirty (30) days or five (5) elimination half-lives of such investigational drug, whichever is longer, prior to study drug administration, or planned administration of another investigational product or procedure during the subject's participation in this study
* Administration of any local anesthetic within 72 hours prior to administration of study drug, other than for pretreatment prior to a needle placement
* Require additional local anesthetic other than study drug or lidocaine used for the Mayo field block or for pretreatment prior to a needle placement during the study period
* Uncontrolled anxiety, psychiatric, or neurological disorder that, in the opinion of the Investigator, could interfere with study assessments or compliance
* Currently pregnant, nursing, or planning to become pregnant during the study
* Clinically significant medical disease that, in the opinion of the Investigator would make participation in a clinical study inappropriate. This includes diabetic neuropathy, coagulation or bleeding disorders, severe peripheral vascular disease, renal insufficiency, hepatic dysfunction, glucose-6-phosphate dehydrogenase deficiency or other conditions that would constitute a contraindication to participation in the study
* Confirmed clinically significant vital sign or ECG abnormality, including QTcF \> 450 msec at Screening
* Has any of the following laboratory abnormalities during Screening (1 retest permitted):

  1. History of liver cirrhosis, having an aspartate aminotransferase \>3x the upper limit of normal (ULN), or having an alanine aminotransferase \> 3x ULN.
  2. Severe kidney function impairment as defined by estimated glomerular filtration rate (eGFR) by CKD-EPI 2021 equation \<30 mL/min/1.73 m²or on dialysis.
  3. Platelet count \< 100,000/uL, hemoglobin \< 12 g/dL, or hematocrit \< 35%.
* Currently on a gabapentinoid (e.g., gabapentin, pregabalin \[Lyrica\]) or a serotonin-norepinephrine reuptake inhibitor (SNRI) with recognized analgesic properties (e.g., duloxetine \[Cymbalta\]) that cannot be discontinued within 30 days before surgery. Other agents with documented efficacy in modulating acute or chronic pain may be excluded at the discretion of the Investigator in consultation with the Sponsor Medical Monitor. Selective serotonin reuptake inhibitors (SSRIs) are not excluded under this criterion.
* Current use of systemic glucocorticoids within thirty (30) days of randomization in this study
* Use of dexmedetomidine HCl or clonidine within three (3) days of study drug administration
* Any use of marijuana (including tetrahydrocannabinol (THC) and cannabidiol (CBD)) within thirty (30) days prior to randomization, or planned use during the study.
* Chronic opioid use within thirty (30) days prior to randomization (average ≥30 oral morphine mg equivalents/day)

Where this trial is running

Millcreek, Utah

• CenExel Salt Lake City — Millcreek, Utah, United States (Recruiting)

Study contacts

• Study coordinator: Caleb Lade, MD

Conditions Hallux Valgus; Bunionectomy; ALX006; Bupivacaine; Popliteal fossa nerve block; Analgesia; Post-operative analgesia