Objective, Endpoints, and Assessments
ocular pain, pain, Ocular Pain, corneal and ocular surface pain, conjunctival redness
ADVERSE EVENTS, CONJUNCTIVA, OCULAR HYPEREMIA
The primary objective was to evaluate pain control in the immediate post-PRK period. The coprimary endpoints were (1) visual analog scale (VAS) pain assessment at 6 hours postoperatively and (2) average ocular pain VAS assessments from the first postoperative assessment up to the 12-hour predose assessment. Secondary endpoints included (1) incidence and amount of ORM needed from 6 hours to 3 days postoperatively after each PRK surgery; (2) adverse events (AEs) and serious AEs (SAEs); (3) size of epithelial defect by slit-lamp exam, visual acuity (VA), blink rate, and tear production; (4) all VAS measurements during the first 3 days after surgery; and (5) plasma concentration and pharmacokinetic (PK) parameters of SAF312.To account for the potential influence of the rescue medication on the primary endpoints, three different approaches of analyzing the VAS pain scores and calculating the average (0–12 hours) were planned in advance and evaluated after data collection. The three different approaches included any recorded VAS pain score at time points within 4 hours after the use of rescue medication, which was imputed by the record taken at the time of rescue medication use. This method was applied as the primary sensitivity analysis, as per the FDA guidance in 2014.The exploratory endpoint included is the Ocular Pain Assessment Survey (OPAS) outcome. OPAS was designed and validated to measure ocular pain and quality of life in patients with corneal and ocular surface pain at initial and follow-up visits in the clinic over a 6-month period.VAS pain assessments were captured digitally in real time with a handheld (electronic patient-reported outcome [ePRO]) device at the protocol-specified time points. VAS uses a numeric assessment of pain between 0 and 100, with 0 representing no pain and 100 representing the worst imaginable pain. Safety assessments consisted of AEs and SAEs, with their severity and relationship to the study drug. Ocular hyperemia was assessed using the McMonnies redness scale (0–5 photographic scale, with higher scores indicating a greater degree of conjunctival redness) in four regions of the bulbar conjunctiva (superior, inferior, temporal, nasal). Each eye and each region were graded by severity (0–5).The details of other assessments performed in the study are provided in 