Topical Ocular TRPV1 Antagonist SAF312 (Libvatrep) for Postoperative Pain After Photorefractive Keratectomy.

Abstract

Evaluation of safety and efficacy of topical ocular SAF312 (Libvatrep) in post-photorefractive keratectomy (PRK) pain. In this placebo (vehicle)-controlled, participant- and investigator-masked study, 40 participants were randomized (1:1) to two treatment sequences in a bilateral PRK crossover design (SAF312 2.5% followed by vehicle [or vice versa], one eye drop, four times daily for 72hours after PRK). Primary endpoints were visual analog scale (VAS) pain scores at 6hours after first drop of study drug and average VAS scores over 0 to 12hours postoperatively. Secondary endpoints included postoperative oral rescue medication (ORM) use and adverse events (AEs). All 40 participants completed the study. Both primary endpoints were met; mean difference in VAS pain scores between SAF312- and vehicle-treated eyes was -11.13 (P = 0.005, -25%) at 6hours postoperatively and -8.56 (P = 0.017, -22%) over 0 to 12hours. Mean VAS pain scores with SAF312 were consistently lower than with vehicle from 1hour postoperatively up to 30hours (P ≤ 0.10 observed in 8/11 time points). Less ORM was taken with SAF312 up to 0 to 72hours postoperatively, with a trend of fewer participants taking ORM at 0 to 24hours postoperatively with SAF312 versus vehicle. No serious AEs were reported. All ocular AEs were mild and transient, and none were drug related. SAF312-treated eyes showed no delay in wound healing and had a lower grade 4 conjunctival hyperemia 24hours postoperatively versus vehicle-treated eyes. SAF312 was well tolerated and effective in reducing ocular pain post-PRK. Topical SAF312 presents a new therapeutic option for patients undergoing PRK.