Results of a Randomized, Double-Masked, Placebo-Controlled Phase 1/2 Study of a TRPV1 Antagonist SJP-0132 in Participants With Dry Eye Disease

PURPOSE: To investigate the safety, tolerability, pharmacokinetic profile, and efficacy of SJP-0132 in participants with dry eye disease (DED). DESIGN: Phase 1/2, randomized, double-masked, single-center, placebo-controlled single and multiple ascending dose study. PARTICIPANTS: Generally healthy adults aged ≥18 years with a patient-reported history of DED for ≥6 months, eye dryness visual analog scale (VAS: 0-100) ≥40 mm, 5-item dry eye questionnaire (DEQ-5) ≥6, and central corneal fluorescein staining (CFS) of 2 to 4 (Baylor scale: 0-5 for each of five zones). METHODS: This study consisted of Part A and Part B, containing four single- and two multiple-ascending dose cohorts, respectively. Following a 14-day placebo run-in, participants were randomized 1:3 to receive a single dose of placebo or SJP-0132 in each cohort in Part A. In Part B, participants were randomized 1:2 to receive placebo or SJP-0132 four times daily for 4 weeks in each cohort. MAIN OUTCOME MEASURES: The primary outcomes were the number and severity of adverse events, plasma concentration, and mean change from baseline in eye dryness VAS at 4 hours on Day 29 and in CFS score at the central zone on Day 29. Secondary end points included total CFS of all 5 zones, conjunctival staining, tear film break-up time, additional dry eye symptom VAS, DEQ-5, and tear matrix metalloproteinase-9. RESULTS: Twenty-nine and 60 participants were randomized to Part A and B, respectively. Two of 21 and 6 of 40 participants who received SJP-0132 in each part reported at least one treatment-emergent adverse event (TEAE), compared with 0 of 8 and 7 of 20 for placebo. All TEAEs were mild. Plasma concentrations increased dose dependently. Eye dryness VAS decreased as early as 30 minutes after the first dose in the 0.1% and 0.3% groups in Part A and in the 0.3% group in Part B. The decrease persisted throughout the treatment period, although it was not statistically significant versus placebo. CFS scores decreased throughout the treatment period with a dose dependence similar to VAS. CONCLUSIONS: SJP-0132 was safe and well tolerated, plasma concentrations increased dose dependently, and efficacy data indicated that it improved both signs and symptoms of DED with a rapid onset of improvement.