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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
60
ALX006 (50 mg/mL bupivacaine free base)
Bupivacaine HCl 0.25% plain (2.5 mg/mL)
Sciatic nerve block in the popliteal fossa
CenExel Salt Lake City
Millcreek, Utah, United States
RECRUITINGIncidence and severity of treatment-emergent adverse events (TEAEs)
TEAEs graded by CTCAE v5.0, summarized by System Organ Class and Preferred Term
Time frame: From start of nerve block procedure through 360 Hour Visit (Day 15)
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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: End of surgery through 168 hours post-surgery
Plasma bupivacaine maximum observed concentration (Cmax)
Maximum observed plasma bupivacaine concentration following single-dose administration
Time frame: 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.
Time frame: Pre-dose through 168 hours post-block administration
Apparent terminal elimination half-life of bupivacaine (t½el)
Apparent terminal elimination half-life of plasma bupivacaine
Time frame: 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.
Time frame: Pre-dose through 168 hours post-block administration
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