CPL-01, an investigational long-acting ropivacaine, demonstrates safety and efficacy in open inguinal hernia repair

H T Xu; J Zimmerman; T Bertoch; L Chen; P J Chen; E Onel

doi:10.1007/s10029-024-03047-3

CPL-01, an investigational long-acting ropivacaine, demonstrates safety and efficacy in open inguinal hernia repair

Hernia. 2024 May 7. doi: 10.1007/s10029-024-03047-3. Online ahead of print.

Authors

H T Xu¹, J Zimmerman², T Bertoch³, L Chen⁴, P J Chen^{5

4}, E Onel⁴

Affiliations

¹ Cali (SZ) Biosciences Co., Ltd. Shanghai Branch, Building 7, 690 Bibo Road, Shanghai, R715S, China. h.xu@calibiosciences.com.
² Trovare Clinical Research, 3838 San Dimas St Ste A280, Bakersfield, CA, 93301, USA.
³ CeneExel JBR, 650 East 4500 South, Suite 100, Salt Lake City, UT, 84107, USA.
⁴ Cali Biosciences US, LLC, 9675 Businesspark Avenue, San Diego, CA, 92131, USA.
⁵ Cali (SZ) Biosciences Co., Ltd. Shanghai Branch, Building 7, 690 Bibo Road, Shanghai, R715S, China.

PMID: 38713429
DOI: 10.1007/s10029-024-03047-3

Abstract

Background: There is an unmet medical need for effective nonopioid analgesics that can decrease pain while reducing systemic opioid use. CPL-01, an extended-release injectable formulation of ropivacaine, is designed to safely provide analgesia and reduce or eliminate opioid use in the postoperative period.

Methods: Subjects undergoing open inguinal hernia with mesh were prospectively randomized to 1 of 3 doses of CPL-01 (10, 20, or 30 ml of 2% CPL-01, n = 14, 12, and 14, respectively), Naropin (150 mg, n = 40), or saline placebo (n = 13) infiltrated into the surgical site prior to closure. Pain and rescue medication usage was assessed, and Numeric Rating Scale (NRS) pain scores were adjusted for opioid usage using windowed worst observation carried forward (wWOCF) imputation. The primary efficacy endpoint was the mean area under the curve (AUC) of the NRS pain intensity scores with activity.

Results: Ninety-three subjects were treated, and 91 subjects completed 72 h of post-operative monitoring. Subjects who received the highest dose of CPL-01 in Cohort 3 showed a clinically meaningful reduction in postoperative pain intensity scores, which was the lowest value for any treatment in all cohorts, showing a trend towards statistical significance as compared to the pooled placebo group (p = 0.08), and numerically better than the 40 subjects who received Naropin. Opioid use through 72 h in subjects who received CPL-01 in Cohort 3 was approximately half of that shown in the placebo and Naropin groups; approximately 2/3 of the CPL-01 subjects (9/14) required no opioids at all through the first 72 h after the operation. More CPL-01 subjects avoided severe pain and were ready for discharge earlier than other groups. CPL-01 was safe and well-tolerated, with no clinically meaningful safety signals, and showed predictable and consistent extended-release pharmacokinetics.

Conclusion: Results suggest that CPL-01 may be the first long-acting ropivacaine to address postoperative pain while reducing the need for opioids.

Keywords: long-acting local anesthetic; non-opioid analgesia; Herniorraphy.