Statistical methods
Two efficacy analysis sets were defined for statistical purposes, the intention-to-treat (ITT) population, which was used for all endpoints, and a per protocol (PP) set, which included participants without major protocol violations that were likely to seriously influence the primary outcome of the study as judged by a masked evaluation prior to the unmasking of the study treatment. Clinical non-inferiority for the experimental drug could be applied if the upper limit of the 95% confidence intervals (CI) around the difference was ≤ 1.5 mmHg at all nine time points through Month 3 and ≤ 1.0 mmHg at the majority of time points (at least five of nine) through Month 3. Each time point within each visit was modelled separately. Assuming no difference between NET/LAT and BIM/TIM, a two-tailed alpha of 0.05 (two-sided 95% CI) at each of the nine time points, a common SD of 3.5 mmHg, and a correlation between time points of 0.6 or less, 200 (ITT) participants per arm were necessary to have 85% power to show clinical non-inferiority (as defined above) for the primary endpoint. A randomization code for allocating the treatments was prepared by an independent biostatistician (Statistics & Data Corporation, Tempe, AZ and Waltham, MA, USA) who was not involved in the day-to-day conduct of the study. Study medication was provided in identical packaging to preserve masking.To evaluate the primary outcome, a linear model was employed with IOP at the given visit and time point as the response, baseline IOP as a covariate, and treatment as a main effect factor at each time point at each visit. Markov Chain Monte Carlo (MCMC) multiple imputation techniques were used to impute missing data.All patients who received at least one dose of treatment were included in the safety analysis population, and assessments took place until study completion or discontinuation.