A randomized, vehicle-controlled, Phase 2b study of two concentrations of the TRPM8 receptor agonist AR-15512 in the treatment of dry eye disease (COMET-1)

Dry eye disease (DED) symptoms can negatively impact quality of life (QoL). AR-15512, a transient receptor potential melastatin 8 (TRPM8) agonist, was evaluated as a potential therapy for DED. In a Phase 2b study, patients with DED were randomized 1:1:1 to 0.0014% AR-15512, 0.003% AR-15512, or vehicle twice daily for 12 weeks. Eligibility criteria included DED signs and symptoms of prespecified severity levels. Outcomes assessed were DED signs (Schirmer score ± anesthetic, ocular surface staining, hyperemia), symptoms (Ocular Discomfort [ODS-VAS], Symptoms Assessment iN Dry Eye [SANDE], Eye Dryness-VAS, Ocular Pain-VAS), QoL-VAS, and adverse events. Co-primary endpoints were changes from baseline in ODS-VAS and anesthetized Schirmer score at Day 28. 0.003% AR-15512 (n = 122) was associated with early and sustained improvements in unanesthetized Schirmer score (Days 1 and 14, p