Efficacy and Safety of SJP-0132 in Patients With Dry Eye Disease: A Phase 2b Randomized, Double-Masked, Dose-Finding Study

OBJECTIVE: Evaluate the efficacy, safety, and optimal dose of the TRPV1 antagonist SJP-0132 ophthalmic suspension in patients with dry eye disease. DESIGN: Randomized, double-masked, multicenter, placebo-controlled, Phase 2b dose-response study in Japan. PARTICIPANTS: Outpatients aged ≥20 years with dry eye-related subjective symptoms (eye dryness visual analog scale score ≥40; 5-item Dry Eye Questionnaire score ≥6), and objective signs (mean tear-breakup time ≤5 seconds in both eyes; corneal fluorescein staining [CFS] score using Baylor criteria: 2 to 4 for central zone of at least one eye, total score 4 to 20 for all zones, and ≥1 for at least one of the four peripheral corneal regions). METHODS: After a 2-week placebo run-in period, patients were randomized 1:1:1:1 to receive SJP-0132 ophthalmic suspension 0.1%, 0.3%, or 1.0%, or placebo, administered as 1 drop in each eye four times daily for 4 weeks. MAIN OUTCOME MEASURES: The primary endpoint was the change from baseline to week 4 in CFS score for all zones with SJP-0132 0.3% vs placebo (primary analysis) and SJP-0132 0.1% or 1.0% vs placebo (secondary analysis). RESULTS: Total 344 patients were randomized and received at least one dose of SJP-0132 0.1% (n = 87), SJP-0132 0.3% (n = 87), SJP-0132 1.0% (n = 85), or placebo (n = 85). For the primary endpoint, there were no statistically significant differences between the SJP-0132 0.3% and placebo groups (between-group difference -0.8; 95% CI -1.7, 0.2; P = .1181), or between the SJP-0132 0.1% (-0.7; 95% CI -1.8, 0.4; P = .1990) or SJP-0132 1.0% (-0.1; 95% CI -1.3, 1.0; P = .8276) and placebo groups. Secondary endpoints showed generally dose-dependent efficacy and safety of SJP-0132. Improvements in subjective symptoms of dry eye, quality of life, and objective signs were observed after 1 week of SJP-0132 administration and maintained through to week 4, with statistically significant differences to placebo observed at some endpoints. Subgroup analyses suggested greater treatment benefits with SJP-0132 0.3% in subgroups based on baseline ocular characteristics. SJP-0132 was generally well tolerated across the dose groups. CONCLUSIONS: SJP-0132 showed generally dose-dependent efficacy and safety. Based on safety and treatment benefits with SJP-0132 0.3% in the overall population and in subgroups, this dose was considered optimal for further development.