PURPOSE: To evaluate the analgesic efficacy of topical ocular BL1312 (formerly SAF312/Libvatrep) for postoperative pain following photorefractive keratectomy (PRK) using the Sum of Pain Intensity Differences method over 0–24 hours (SPID24), aligned with FDA guidance on development of non-opioid analgesics for acute pain. The original coprimary endpoints, mean VAS difference at 6 hours (−11.1 mm; p=0.005) and average VAS difference over 0–12 hours (−8.6 mm; p=0.017), were statistically significant.

METHODS: In a Phase 2a randomized, double-masked, vehicle-controlled, bilateral crossover study (NCT02961062), 40 participants undergoing bilateral PRK were randomized 1:1 to two treatment sequences: BL1312 in period 1 after PRK in the nondominant eye followed by vehicle in period 2 after PRK in the fellow eye, or the reverse sequence of study treatment ordering. BL1312 2.5% and vehicle were administered as single drops four times daily (every 6 hours) for 72 hours postoperatively. Pain was assessed using a visual analog scale (VAS) at multiple time points. Data were reanalyzed using SPID24, calculated by the trapezoidal rule. Additional analyses using SPID over 0–12 hours was also performed. Statistical tests used a linear mixed model fit by REML using 0.95% 2-sided confidence level and Kenward-Roger degrees-of-freedom method.

RESULTS: BL1312 demonstrated statistically significantly greater pain reduction in terms of cumulative change in pain compared with vehicle over 0–24 hours (SPID24: −184; p=0.0131). Significant benefit was also observed over 0–12 hours (SPID12: −89.8; p=0.0266) These findings corroborate the original primary analyses and demonstrate consistent pain reduction with BL1312 across the 24-hour postoperative period.

CONCLUSIONS: Use of the cumulative SPID24 endpoint confirms the clinical efficacy of topical BL1312 in delivering significant postoperative pain relief over 24 hours following PRK. This reanalysis provides robust and clinically relevant support for BL1312 as a non-opioid option for management of acute post-PRK pain.