Abstract
Purpose :
Dry eye disease (DED) is a symptomatic ocular surface condition that imposes a substantial health burden and can affect a patient’s daily activities and quality of life (QoL). AR-15512 is a TRPM8 cold thermoreceptor agonist that stimulates both tear production and a cooling sensation across the ocular surface. A phase 2b study was conducted to evaluate DED symptoms and QoL following administration of AR-15512.
Methods :
Prospective, double-masked study evaluating two formulations of AR-15512 (0.0014% and 0.003%) versus vehicle dosed twice daily for 84 days in 369 DED subjects. Following vehicle run-in, eligible subjects were randomized 1:1:1 and evaluated where applicable at Days 1, 14, 28 and 84. Outcomes included tear production (unanesthetized Schirmer test, performed at D1 and D14 only), symptoms (Symptom Assessment iN Dry Eye [SANDE] and visual analog scales [VAS] for ocular discomfort [ODS] and eye dryness [EDS]) and QoL (7 VAS questions evaluating activities of daily living: driving, workplace productivity, reading books, reading fine print, using electronic devices, watching TV, and feeling depressed).
Results :
Overall, 369 subjects enrolled (mean age 63.7; 72% female) and of these, 345 (93.5%) completed the study. Statistically significant improvements were achieved in the ITT population with 0.003% AR-15512 vs vehicle for both signs and multiple symptoms. Increased tear production was observed after initial dose and repeat dosing (D1: 20.2 vs 8.1mm and D14: 19.5 vs 5.9mm, p<0.0001). Symptom improvements were observed as follows: SANDE on D14 (-7.4 vs -2.9, p=0.0254), D28 (-12.9 vs -5.0, p=0.0005) and D84 (-17.2 vs -8.3, p=0.0015), ODS (-20.6 vs -13.6, p=0.0281) and EDS (-17.1 vs -10.8, p=0.0302) at D84. Lastly, statistically significant improvements (p<0.05) from baseline were also seen with 0.003% AR-15512 relative to vehicle on all 7 QoL measures as early as D14, with the magnitude of difference relative to vehicle continuing to widen throughout the 84-day study on most of the measures. AR-15512 was well tolerated, with few discontinuations (n=7; 1.9%) due to adverse events.
Conclusions :
In addition to improving signs and symptoms, 0.003% AR-15512 demonstrated improvements in functional vision which were observed within 2 weeks and continued to improve over time. AR-15512 represents a novel treatment for DED with the potential to improve patient quality of life.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.