Double-Masked Controlled Trial of H-1337 as a Treatment for Glaucoma and Ocular Hypertension

PURPOSE: Extend Phase 2A study to evaluate additional concentrations of H-1337 and dosing frequencies, and to compare them with a positive control. DESIGN: Phase 2B, randomized, double-masked, active-controlled, dose-response study of 28 days of four treatments: H-1337 0.6% b.i.d., 1.0% b.i.d., or 1.0% q.d. (1.0% in the morning with H-1337 vehicle in the evening), and timolol maleate 0.5% b.i.d. PARTICIPANTS: Two hundred one subjects with open-angle glaucoma or ocular hypertension at eight private practice sites in the United States. METHODS: Diurnal intraocular pressure (IOP) over 28 days of dosing. MAIN OUTCOME MEASURES: Non-inferiority to timolol in change from baseline in IOP at Day 1 and Day 28. RESULTS: Mean reduction in IOP was 4-7 mmHg for the H-1337 groups and 5-8 mmHg for the timolol group. Non-inferiority to timolol for H-1337 1.0% b.i.d. [upper limit of 95% confidence interval (CI) strictly lower than 1.5 mmHg] was met at 6/9 time points (Day 1: h 8 and 12; Day 28: h 2, 4, 8, and 12). Similar comparative efficacy was seen for the other H-1337 treatment groups. The most common adverse event observed was hyperemia, reported in 54.0% (27/50) for H-1337 1.0% q.d., 33.3% (17/51) for H-1337 0.6% b.i.d., 41.2% (21/51) for H-1337 1.0% b.i.d., and 8.2% (4/49) for timolol. CONCLUSION: H-1337 in doses of 0.6% b.i.d., 1.0% q.d., and 1.0% b.i.d. had ocular hypotensive efficacy in the range of timolol, although not within the strict Phase 3 non-inferiority margins, which would have required a larger sample size.