Lotus Clinical Research has worked with Concentric for several years and through multiple studies on their novel non-opioid analgesic vocacapsaicin. Recently, Lotus CRO has been instrumental in the study design, protocol writing and development, statistical analysis, management and oversight of Concentric’s total knee arthroplasty clinical trials at Lotus sites. Lotus also conducted Concentric’s earlier bunion and abdominoplasty clinical trials as a CRO and clinical site, and is now supporting Concentric’s hernia study.
Concentric Analgesics Announces Positive Topline Results from Phase 2 Clinical Trial of Vocacapsaicin (CA-008) in Total Knee Arthroplasty Surgery
Statistically Significant and Clinically Meaningful Reductions in Pain Lasting At Least One Week vs. Active Control
Need for Opioids Reduced by 31% During First Week Following Surgery
December 16, 2020 08:00 AM Eastern Standard Time
SAN FRANCISCO–(BUSINESS WIRE)–Concentric Analgesics, Inc., a clinical-stage biopharmaceutical company focused on developing and commercializing novel, non-opioid pain therapeutics, today announced positive topline results from its recently completed Phase 2 clinical trial of vocacapsaicin (CA-008), a first-in-class, non-opioid therapeutic with FDA Breakthrough Therapy Designation. The primary objectives of the study, conducted in 187 patients undergoing total knee arthroplasty (“TKA”), were to evaluate the effects on reported pain, opioid consumption, safety and pharmacokinetics of vocacapsaicin over 7 days.
“The therapeutic profile demonstrated by vocacapsaicin in this study is compelling and is ideally suited for the vast majority of orthopedic surgeries”
The study showed that vocacapsaicin, administered during surgery at a dose of 36 mg, achieved statistically significant and clinically meaningful reductions in both pain and opioid consumption. During the first 4 days (0-96 hours), vocacapsaicin reduced pain with activity, as measured by the pain intensity area under the curve (AUC), by 21% (p=0.0006) and pain at rest by 17% (p=0.0012) compared to the control group. During the same period, vocacapsaicin reduced opioid consumption by 30% (p<0.0001) compared to the control group, treated with placebo plus standard of care.
The statistically significant and clinically meaningful analgesic effect for the 36 mg dose of vocacapsaicin lasted at least through 7 days. For the period 0 – 168 hours, vocacapsaicin reduced pain with activity, as measured by the pain intensity AUC, by 17% (p=0.0072) and pain at rest by 15% (p=0.01) compared to the control group. During the first 7 days (0-168 hours), opioid consumption was reduced by 31% (p<0.0001) compared to the control group.
Vocacapsaicin generally appeared safe and well tolerated compared to the control group.
“The study was well designed and properly powered for proof-of-efficacy, and the results are impressive,” said Harold S. Minkowitz, MD, Director Acute Pain and Hospital Based Research at HD Research LLC in Houston, Texas, and a participating investigator in the study. “Over the past 20 years, I have participated in over 150 studies involving treatments for acute postsurgical pain, with many specifically evaluating pain following total knee arthroplasty. The effects of vocacapsaicin on pain relief and reduction of opioid consumption are unprecedented, and speaking as an anesthesiologist, the promise of vocacapsaicin is considerable.”
Rishi Balkissoon, MD, MPH, Assistant Professor University of Rochester and an orthopedic surgeon specializing in primary and revision total hip and knee replacement surgery, stated, “It’s a remarkable achievement to see clinically meaningful reductions in pain and opioid consumption that are not simply within the first 1-2 days. Vocacapsaicin has the potential to provide a clear therapeutic benefit for TKA patients during the critical and often challenging period immediately following discharge.”
“The therapeutic profile demonstrated by vocacapsaicin in this study is compelling and is ideally suited for the vast majority of orthopedic surgeries,” said Michael D. Maloney, MD, Dean’s Professor of Orthopaedics, Chief, Division of Sports Medicine, and Medical Director, Ambulatory Surgery Center at University of Rochester Medical Center. “A therapeutic that can minimize or eliminate the need for opioids in the postsurgical and rehabilitation periods would provide tremendous clinical and societal impact. If the clinical benefits seen in TKA can be extended to other orthopedic procedures, vocacapsaicin has the potential to become a new standard of care.”
The randomized, double-blind, placebo-controlled, dose-finding study enrolled 187 patients undergoing total knee arthroplasty and compared the safety and efficacy of vocacapsaicin to a standard of care, active control. During surgery, all patients received a standard of care that included spinal anesthesia, ketorolac, acetaminophen, and ropivacaine (joint infiltration, femoral nerve and IPACK blocks). The study was comprised of two arms receiving vocacapsaicin 36 mg (n=61) and 60 mg (n=62) and a standard-of-care, placebo control arm with active opioid rescue (n=64). Vocacapsaicin, a prodrug of capsaicin, was administered via infiltration to the surgical site. The primary efficacy endpoint of the Phase 2 study was reduction in pain at rest (AUC) from 12-96h, with key secondary endpoints including pain and opioid consumption over 0-96h and over 0-168h post-surgery.
Efficacy Results Summary
Patients were evaluated for pain intensity using the standard Numerical Rating Scale (NRS), as measured by the area under the curve (AUC) during specified intervals. Key secondary endpoints that were evaluated included opioid consumption, pain intensity over two weeks at rest and with ambulation, readiness for early discharge, along with standard safety measures and PK sample collections.
Vocacapsaicin 36 mg showed statistically significant and clinically meaningful results, including:
In this dose finding study, the overall response observed with vocacapsaicin 36 mg was consistently better than that observed with the 60 mg dose.
Safety Results Summary
The safety profile of vocacapsaicin was evaluated in the standard research manner by serial assessments of adverse events, vital signs, physical examination, surgical wound healing and laboratory testing. Vocacapsaicin generally appeared safe and well-tolerated. All parameters appeared consistent with a benign safety profile compared to the control group with no local or systemic safety concerns identified.
“Today’s results confirm vocacapcascin’s unique and compelling therapeutic profile in a second important surgical model,” said Frank Bellizzi, DMD, Chief Executive Officer of Concentric Analgesics. “Recognizing the dearth of true innovation in therapeutics for managing postsurgical pain, and the adverse societal impact caused by our national opioid crisis, we are redoubling our efforts to complete development and rapidly bring vocacapsaicin to market.”
The company expects to announce the full study results in January and plans to present complete data from the Phase 2 clinical trial at upcoming scientific meetings in 2021.
Based on the positive Phase 2 dose-ranging study results in two surgical models – TKA and the previously reported results in bunionectomy – the company has identified the effective dose level of vocacapsaicin. An End of Phase 2 Meeting with the FDA is scheduled in April 2021. Based on the available Phase 2 results and discussions with the FDA, the company will evaluate additional surgical models while finalizing plans for Phase 3.
About Opioid Addiction & Post-Surgical 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, approximately 50,000 Americans died from opioid overdoses in 2018 – 30% more than the total number of deaths from automobile accidents. New approaches for preventing this insidious disease are imperative, including in the postsurgical setting, which can be an unsuspecting 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 in 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 a week or more. Vocacapsaicin has received both Fast Track Designation (2017) and Breakthrough Therapy Designation (2018) from FDA.
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 injection. Vocacapsaicin, in Phase 2 development, is the company’s lead product candidate for postsurgical pain. Concentric has two additional active programs for multiple 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.