Sciatic Nerve Block With ALX006 in Subjects Undergoing Bunionectomy

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 is a Phase 2, randomized, double-blind, active-controlled, dose-escalation study evaluating the safety, pharmacokinetics, efficacy, and pharmacodynamics of ALX006, an extended-release bupivacaine formulation, administered as a single-dose sciatic nerve block in the popliteal fossa in adult subjects undergoing primary unilateral bunionectomy. Approximately 60 subjects will be enrolled across 3 sequential dose cohorts (100 mg, 150 mg, 200 mg ALX006), with each cohort comparing ALX006 against MARCAINE 0.25% (bupivacaine HCl 50 mg) as the active comparator at a 3:1 randomization ratio. Dose escalation between cohorts is governed by an Independent Data Monitoring Committee.

Study Overview

• Status: Recruiting
• Conditions: Hallux Valgus; Bunionectomy
• Intervention / Treatment: Drug: ALX006 (bupivacaine extended-release injection); Procedure: Sciatic Nerve Block; Drug: Bupivacaine Hcl 0.25% Inj

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Caleb Lade, MD; Phone Number: 918-808-8399; Email: caleb.lade@rebelmedicine.com

Study Locations

• United States
  • Utah
    • Millcreek, Utah, United States, 84107
      • Recruiting
      • CenExel Salt Lake City
      • Principal Investigator: Todd Bertoch, MD
      • Contact: Director of Clinical Operations; Phone Number: (801) 261-2000; Email: s.zunkowski@cenexel.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALX006 100 mg; Single-dose ALX006 100 mg (50 mg/mL bupivacaine free base) administered as ultrasound-guided sciatic nerve block in the popliteal fossa, 60 min (±15 min) prior to bunionectomy.	Drug: ALX006 (bupivacaine extended-release injection); ALX006 (50 mg/mL bupivacaine free base); Procedure: Sciatic Nerve Block; Sciatic nerve block in the popliteal fossa; Other Names: Sciatic Nerve Block in the Popliteal Fossa
Experimental: ALX006 150 mg; Single-dose ALX006 150 mg (50 mg/mL bupivacaine free base) administered as ultrasound-guided sciatic nerve block in the popliteal fossa, 60 min (±15 min) prior to bunionectomy.	Drug: ALX006 (bupivacaine extended-release injection); ALX006 (50 mg/mL bupivacaine free base); Procedure: Sciatic Nerve Block; Sciatic nerve block in the popliteal fossa; Other Names: Sciatic Nerve Block in the Popliteal Fossa
Experimental: ALX006 200 mg; Single-dose ALX006 200 mg (50 mg/mL; bupivacaine free base) administered as ultrasound-guided sciatic nerve block in the popliteal fossa, 60 min (±15 min) prior to bunionectomy.	Drug: ALX006 (bupivacaine extended-release injection); ALX006 (50 mg/mL bupivacaine free base); Procedure: Sciatic Nerve Block; Sciatic nerve block in the popliteal fossa; Other Names: Sciatic Nerve Block in the Popliteal Fossa
Active Comparator: MARCAINE 0.25%; Single-dose MARCAINE 0.25% (bupivacaine HCl 50 mg; 20 mL), administered as ultrasound-guided sciatic nerve block in the popliteal fossa, 60 min (±15 min) prior to bunionectomy.	Procedure: Sciatic Nerve Block; Sciatic nerve block in the popliteal fossa; Other Names: Sciatic Nerve Block in the Popliteal Fossa; Drug: Bupivacaine Hcl 0.25% Inj; Bupivacaine HCl 0.25% plain (2.5 mg/mL); Other Names: MARCAINE 0.25%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of treatment-emergent adverse events (TEAEs)	TEAEs graded by CTCAE v5.0, summarized by System Organ Class and Preferred Term	From start of nerve block procedure through 360 Hour Visit (Day 15)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC of NRS pain intensity scores 0-72 hours post-surgery	Area under the curve of 11-point Numeric Rating Scale (0 = no pain; 10 = worst possible pain) for current pain in operative foot	0 to 72 hours post-surgery
AUC of NRS pain intensity scores 0-96 hours post-surgery	Area under the curve of 11-point Numeric Rating Scale (0 = no pain; 10 = worst possible pain) for current pain in operative foot	0 to 96 hours post-surgery
AUC of NRS pain intensity scores 0-120 hours post-surgery	Area under the curve of 11-point Numeric Rating Scale (0 = no pain; 10 = worst possible pain) for current pain in operative foot	0 to 120 hours post-surgery
Total postsurgical opioid consumption in oral morphine equivalents (OMED) from 0 to 72 hours post-surgery	Cumulative opioid consumption from the end of surgery through 72 hours, calculated as oral morphine equivalent dose (OMED) using CDC opioid morphine equivalent conversion factors.	0 to 72 hours post-surgery
Total postsurgical opioid consumption in oral morphine equivalents (OMED) from 0 to 96 hours post-surgery	Cumulative opioid consumption from the end of surgery through 96 hours, calculated as oral morphine equivalent dose (OMED) using CDC opioid morphine equivalent conversion factors.	0 to 96 hours post-surgery
Total postsurgical opioid consumption in oral morphine equivalents (OMED) from 0 to 120 hours post-surgery	Cumulative opioid consumption from the end of surgery through 120 hours, calculated as oral morphine equivalent dose (OMED) using CDC opioid morphine equivalent conversion factors.	0 to 120 hours post-surgery
Percentage of opioid-free subjects through 72 hours post-surgery	Proportion of subjects who consumed no opioid medication from the end of surgery through 72 hours.	0 to 72 hours post-surgery
Percentage of opioid-free subjects through 96 hours post-surgery	Proportion of subjects who consumed no opioid medication from the end of surgery through 96 hours.	0 to 96 hours post-surgery
Percentage of opioid-free subjects through 120 hours post-surgery	Proportion of subjects who consumed no opioid medication from the end of surgery through 120 hours.	0 to 120 hours post-surgery
Median time to first postsurgical opioid consumption	Time from end of surgery to administration of the first postsurgical opioid dose.	End of surgery through 168 hours post-surgery
Plasma bupivacaine maximum observed concentration (Cmax)	Maximum observed plasma bupivacaine concentration following single-dose administration	Pre-dose through 168 hours post-block administration
Time to maximum plasma bupivacaine concentration (Tmax)	Time from end of block administration to the maximum observed plasma bupivacaine concentration.	Pre-dose through 168 hours post-block administration
Apparent terminal elimination half-life of bupivacaine (t½el)	Apparent terminal elimination half-life of plasma bupivacaine	Pre-dose through 168 hours post-block administration
Apparent clearance of bupivacaine (CL/F)	Apparent clearance of bupivacaine following perineural administration, derived by non-compartmental analysis.	Pre-dose through 168 hours post-block administration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median time to onset of sensory block	Median time from end of block administration to the earliest timepoint with loss of light touch sensation along the distribution of the target nerve distal to the block site	From end of block administration through 168 hours
Median duration of sensory block	Median time between onset and offset of sensory block, where offset is defined as the first timepoint of return of light touch sensation in both test areas in a single assessment.	From end of block administration through 168 hours
Median time to onset of motor block	Median time from end of block administration to the earliest timepoint with partial or no foot movement	From end of block administration through 168 hours
Median duration of motor block	Median time between onset and offset of motor block, where offset is defined as resolution of motor block with complete foot movement (dorsiflexion and plantar flexion)	From end of block administration through 168 hours

Collaborators and Investigators

• Sponsor: Rebel Medicine Inc
• Investigators: Study Director: Jayant Agarwal, MD, Rebel Medicine Inc

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2026
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: April 28, 2026
• First Submitted That Met QC Criteria: May 4, 2026
• First Posted (Actual): May 7, 2026

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Analgesia; Bupivacaine; Post-operative analgesia; ALX006; Popliteal fossa nerve block
• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Neurobehavioral Manifestations; Perceptual Disorders; Foot Deformities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Agnosia; Hallux Valgus; Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Bupivacaine
• Other Study ID Numbers: RBL-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No