Safety and Efficacy of Vocacapsaicin for Management of Postsurgical Pain: A Randomized Clinical Trial

Our first peer reviewed clinical report is currently in press at ANESTHESIOLOGY. The journal pre-proof is available online.

Steven L. Shafer, MD; Sam L Teichman, MD; Ira J. Gottlieb, DPM, DABPS; Neil Singla, MD; Harold S Minkowitz, MD; David Leiman, MD; Benjamin Vaughn, MS, RAC; John F. Donovan, MD

April 25, 2024

Background: Nonopioid management of postsurgical pain remains a major unmet need. Few studies have evaluated TRPV1 agonists for analgesia after surgery. We studied intraoperative vocacapsaicin, a novel prodrug of the TRPV1 agonist capsaicin, in a validated model of postsurgical pain.

Methods: This was a triple-blinded, randomized, placebo-controlled, dose-ranging trial in patients undergoing bunionectomy. We randomized patients 1:1:1:1 to surgical site administration of 14 mL of placebo or one of three vocacapsaicin concentrations: 0.30, 0.15, or 0.05 mg/mL. The prespecified primary endpoint was the area-under-the-curve of the Numerical Rating Scale (NRS) pain score at rest through 96 hours for the 0.3 mg/mL group. Prespecified ordered, secondary endpoints for the 0.3 mg/mL group included percent of patients who did not require opioids from 0-96 hours, total opioid consumption through 96 hours, and the area-under-the-curve of the NRS pain score for the first week.

Results: We randomized 147 patients. During the first 96 hours, vocacapsaicin 0.30 mg/mL reduced pain at rest by 33% vs. placebo (primary endpoint, 95% CI [10%, 52%], effect size (Cohen’s D) = 0.61, p = 0.005). Twenty-six percent of patients receiving vocacapsaicin 0.30 mg/mL did not require postoperative opioids for analgesia (p=0.025) vs. 5% of patients receiving placebo. Vocacapsaicin 0.30 mg/mL reduced opioid consumption over the first 96 hours by 50% vs. placebo (95% CI [26%, 67%], effect size = 0.76, p = 0.002). Vocacapsaicin 0.30 mg/mL reduced pain over the first week by 37% vs. placebo (95% CI [12%, 57%], effect size = 0.62, p = 0.004). Treatment effect persisted for at least 2 weeks. All study endpoints showed an administered concentration vs. response relationship. Vocacapsaicin was well-tolerated with no differences between groups in any safety parameter.

Conclusions: A single, local administration of vocacapsaicin during surgery reduced pain and opioid consumption for at least 96 hours after surgery compared to control.

Trial Registration: ClinicalTrials.gov NCT03599089

Link: https://doi.org/10.1097/ALN.0000000000005027

About Opioid Addiction & Postsurgical Pain
Opioid addiction in the United States has reached epidemic proportions, destroying families, lives and communities throughout the country. According to the Centers for Disease Control and Prevention, over 90,000 Americans died from opioid overdoses in 2020 – more than the annual total number of deaths from automobile accidents and gun deaths combined. New approaches for preventing this insidious disease are imperative, including in the postsurgical setting, which can be a significant gateway to prescription pain medicine abuse and beyond. A 2016 US News & World Report revealed that one in 10 patients report becoming addicted or dependent on opioids following surgery. With more than 100 million surgeries performed in the U.S. in 2017, 30 million of which required postsurgical pain management with products that were not over-the-counter (OTC) drugs, the mandate to develop safe and effective non-opioid alternatives is clear.

About Vocacapsaicin (CA-008)
Concentric Analgesics’ lead product candidate for postsurgical pain is a first-in-class prodrug therapeutic that rapidly converts to capsaicin, a potent TRPV1 agonist. Unlike local anesthetics, capsaicin selectively desensitizes pain-conducting nerve fibers without producing sensory numbness or motor weakness. Vocacapsaicin, injected as an aqueous solution during surgery, has the potential to reduce, and in some patients, eliminate the need for opioids in the postsurgical recovery period and provide clinically meaningful pain relief for two weeks. Vocacapsaicin has received both Fast Track Designation (2017) and Breakthrough Therapy Designation (2018) from the U.S. Food and Drug Administration.

About Concentric Analgesics
Concentric Analgesics is a clinical-stage, biopharmaceutical company focused on developing and commercializing novel, non-opioid pain therapeutics. The company’s portfolio of proprietary products is designed to provide long-lasting, selective pain relief after a single local administration. The company is initiating Phase 3 studies for vocacapsaicin, its lead product candidate for postsurgical pain. Concentric has two additional active programs for indications with significant unmet medical need: osteoarthritis pain and chronic refractory pain. For more information, please visit the company’s website at: www.concentricanalgesics.com.

For More Information:
Frank Bellizzi
Chief Executive Officer
Concentric Analgesics, Inc.
frank@concentricanalgesics.com