Efficacy, safety, and pharmacokinetics of CPL-01, an investigational long-acting ropivacaine, in bunionectomy: Results of a phase 2b study.

Abstract

CPL-01 (ropivacaine extended-release injection) is formulated to safely provide postoperative analgesia and reduce opioid use. Participants undergoing unilateral distal first metatarsal bunionectomy with osteotomy were randomized to receive either CPL-01 (200 mg in Cohort 1, 300 mg in Cohort 2), ropivacaine HCl (50 mg in Cohort 1, 75 mg in Cohort 2), or volume-matched placebo into the surgical site prior to closure. Participants remained in an inpatient setting for 72 h to assess efficacy (Numeric Rating Scale [NRS] scores for pain with activity adjusted for opioid usage, and rescue medication usage), safety and pharmacokinetics. Seventy-three participants were randomized and treated, and 71 participants completed the study. Participants who received 300 mg CPL-01 had a mean (SD) area under the curve from 0 to 72 h (AUC_0-72) of the NRS score with activity of 356.9 (132.82), which was lower than placebo, indicating less pain. Participants who received CPL-01 300 mg also had numerically lower mean total opioid consumption. CPL-01 was safe and well-tolerated, with no evidence of increased AEs in one group versus another. Infiltration of CPL-01 had no impact on wound or bone healing. CPL-01 showed predictable and consistent extended-release pharmacokinetics, with no indication of "dose-dumping." Ropivacaine HCl delivered 94.3-99.7 % of its ropivacaine dose in the first 24 h; the 300 mg CPL-01 dose delivered 38.5 %. While this Phase 2b study was small, results demonstrated the safety, efficacy, and extended-release characteristics of this long-acting ropivacaine formulation in this surgical model, supporting further development of CPL-01 in Phase 3 clinical studies. LEVEL OF CLINICAL EVIDENCE: 1.