Aerie 2017.

Study characteristics
Methods	Study design: randomized controlled trial Study grouping: parallel group Unit of randomization: participant Total number of participants (eyes) randomized: 42 participants Number of participants (eyes) randomized per group: placebo: 15, netarsudil 0.02%: 15, netarsudil 0.04%: 12 participants Total number of participants (eyes) lost to follow‐up: 1 participant lost to follow‐up, 2 participants excluded from analysis Number of participants (eyes) lost to follow‐up per group: placebo: 1, netarsudil 0.02%: 1, netarsudil 0.04%: 0 participants Power calculation and sample size consideration reported: yes Planned length of follow‐up: 28 days Actual length of follow‐up: 28 days How missing outcome data were handled: Monte Carlo Markov Chain multiple imputation techniques Was the trial single/double/triple‐masked: triple‐masked (NCT), double‐masked (protocol) Was the trial an equivalence/superiority/non‐inferiority study: superiority Extracted outcome results were based on ITT/mITT/CC/PP/PT analysis: mITT Duration of washout for each drug class before interventions began: 4 weeks (prostaglandins and BBs); 2 weeks (adrenergic agonists); 5 days (muscarinic agonists, carbon anhydrase inhibitors)
Participants	Baseline characteristics Placebo Female, n (%): 8 (66.7%) Age, mean: 65.6 (SD 14.98) years Age ≥ 65 years, n (%): 6 (50%) Number of participants randomized: 12 Number of participants analyzed: 12 Netarsudil 0.02%, once per day (p.m.) Female, n (%): 10 (71.4%) Age, mean: 61.1 (SD 20.32) years Age ≥ 65 years, n (%): 6 (42.9%) Number of participants randomized: 14 Number of participants analyzed: 14 Netarsudil 0.04%, once per day (p.m.) Female, n (%): 11 (78.6%) Age, mean: 60.9 (SD 12.12) years Age ≥ 65 years, n (%): 6 (42.9%) Number of participants randomized: 14 Number of participants analyzed: 14 Overall Female, n (%): 29 (72.5%) Age, mean: 62.4 (SD 15.95) years Age ≥ 65 years, n (%): 18 (45%) Number of participants randomized: 40 Number of participants analyzed: 40 Inclusion criteria: aged ≥ 18 years; of Japanese ethnicity within the second generation defined as (a) first generation born in Japan, immigrated to US and (b) second generation – parents are first generation and the patient was born in US as an American citizen; diagnosis of OAG or OHT in both eyes; medicated IOP ≥ 15 mmHg and < 30 mmHg in both eyes at screening OAG eyes, unmedicated IOP ≥ 15 mmHg and < 35 mmHg at 2 qualification visits at 8 a.m., 10 a.m. and 4 p.m.; OHT eyes, unmedicated IOP ≥ 22 mmHg and < 35 mmHg at 8 a.m., 10 a.m. and 4 p.m.; best corrected visual acuity + 1.0 logMAR or better by ETDRS in each eye; able to give signed informed consent and follow instructions Exclusion criteria: clinically significant ocular disease; pseudoexfoliation or pigment dispersion component glaucoma, history of angle closure glaucoma or narrow angles; IOP ≥ 35 mmHg in either eye; ocular hyperemia score of moderate (+2) at qualification visit #2; previous glaucoma intraocular surgery; refractive surgery in either eye; ocular injury within 6 months prior to screening or ocular surgery or non‐refractive laser treatment within 3 months prior to screening; recent or current ocular infection or inflammation in either eye; use of ocular medication in either eye of any type within 30 days of screening and throughout the study; mean central corneal thickness > 620 µm in either eye; any abnormality preventing reliable applanation tonometry of either eye; known hypersensitivity to benzalkonium chloride or excipients of netarsudil ophthalmic solution; clinically significant abnormalities in screening laboratory tests; clinically significant systemic disease that might interfere with the study; participated in any investigational study within 30 days prior to screening; systemic medication that could have a substantial effect on IOP within 30 days prior to screening or anticipated during the study; women of child‐bearing potential who are pregnant, breast‐feeding, planning a pregnancy or not using a medically acceptable form of birth control Pretreatment: no formal comparison results reported
Interventions	Placebo Netarsudil 0.02%, once per day (p.m.) Netarsudil 0.04%, once per day (p.m.)
Outcomes	Primary outcome reported (time points assessed and reported)  Mean diurnal IOP at week 4 Other outcomes reported (time points assessed and reported) Extent of exposure in days Mean diurnal IOP at days 8 and 15 Mean change from baseline in mean diurnal IOP at each post‐treatment visit Mean IOP at each post‐treatment time point Mean change from diurnally adjusted baseline IOP at each post‐treatment time point Mean percent change from diurnally adjusted baseline IOP at each post‐treatment time point Percentages of participants achieving prespecified mean, mean change and percent mean change in mean diurnal IOP levels Adverse events
Identification	Sponsorship source: Aerie Pharmaceuticals Country: USA Setting: 40 locations Online trial registration site: ClinicalTrials.gov Trial registration #: NCT03310580 Phase of trial: phase 2 Current publication reported findings from > 1 trial: no Year publication accepted: 2019 (results posted) Year study initiation (participants screening, enrollment and treatment): 2017
Notes	Other study ID: AR‐13324‐CS205