Walters 2019 (MERCURY‐2).

Study characteristics
Methods	Study design: randomized controlled trial Study grouping: parallel group Unit of randomization: participant Total number of participants (eyes) randomized: 750 participants Number of participants (eyes) randomized per group: netarsudil: 245, latanoprost: 255, netarsudil/latanoprost: 250 participants Total number of participants (eyes) lost to follow‐up: 3 participants Number of participants (eyes) lost to follow‐up per group: netarsudil: 1, latanoprost: 0, netarsudil/latanoprost: 2 participants Power calculation and sample size consideration reported: yes Planned length of follow‐up: 3 months Actual length of follow‐up: 3 months How missing outcome data were handled: missing data were imputed using Markov Chain Monte Carlo multiple imputation techniques Was the trial single/double/triple‐masked: double‐masked Was the trial an equivalence/superiority/non‐inferiority study: superiority Extracted outcome results were based on ITT/mITT/CC/PP/PT analysis: ITT Duration of washout for each drug class before interventions began: 4 weeks for PAs or BBs, 2 weeks for adrenergic agonists and 5 days for muscarinic agonists or carbonic anhydrase inhibitors
Participants	Baseline characteristics Netarsudil 0.02%, once per day (p.m.) Female, n (%): 153 (60%) Age, mean: 64.5 (SD 10.58) years Age ≥ 65 years, n (%): 146 (57.3%) POAG, n (%): 187 (73.3%) Time since diagnosis to study entry, mean: 339.7 (SD 360.49) weeks Receiving a glaucoma medication within 30 days of baseline screening, n (%): 161 (63.1%) Duration on current ocular hypotensive therapy, mean: 138.7 (SD 197.94) weeks Number of participants randomized: 255 Number of participants analyzed: 228 Latanoprost 0.005%, once per day (p.m.) Female, n (%): 144 (57.6%) Age, mean: 64.3 (SD 11.41) years Age ≥ 65 years, n (%): 138 (55.2%) POAG, n (%): 171 (68.4%) Time since diagnosis to study entry, mean: 360 (SD 380.51) weeks Receiving a glaucoma medication within 30 days of baseline screening, n (%): 167 (66.8%) Duration on current ocular hypotensive therapy, mean: 146 (SD 211.98) weeks Number of participants randomized: 250 Number of participants analyzed: 236  Netarsudil 0.02%/latanoprost 0.005% (FDC), once per day (p.m.) Female, n (%): 152 (62%) Age, mean: 64.2 (SD 11.81) years Age ≥ 65 years, n (%): 127 (51.8%) POAG, n (%): 172 (70.2%) Time since diagnosis to study entry, mean: 317.5 (SD 325.84) weeks Receiving a glaucoma medication within 30 days of baseline screening, n (%): 159 (64.9%) Duration on current ocular hypotensive therapy, mean: 158.8 (SD 227.23) weeks Number of participants randomized: 245 Number of participants analyzed: 228 Overall Female, n (%): 449 (59.9%) Age, mean: 64.3 (SD 11.26) years Age ≥ 65 years, n (%): 411 (54.8%) POAG, n (%): 530 (70.67%) Time since diagnosis to study entry, mean: 339.2 (SD 187.1) Receiving a glaucoma medication within 30 days of baseline screening, n (%): 487 (64.9%) Duration on current ocular hypotensive therapy, mean: 147.7 (SD 212.4) weeks Number of participants randomized: 750 Number of participants analyzed: 692 Inclusion criteria: ≥ 18 years (≥ 19 years in Canada); diagnosis of OAG or OHT in both eyes; unmedicated IOP > 20 mmHg and < 36 mmHg in both eyes at 2 qualification visits; BCVA equivalent to 20/200 Snellen or better; able to give informed consent and follow study instructions Excluded criteria: clinically significant ocular disease; pseudoexfoliation or pigment dispersion component glaucoma, history of angle closure or narrow angles; unmedicated IOP ≥ 36 mmHg in either eye or use of > 2 ocular hypotensive medications within 30 days of screening; known hypersensitivity to any component of the formulation or latanoprost; previous glaucoma surgery or refractive surgery; ocular trauma within 6 months prior to screening; any 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 of the study; mean central corneal thickness > 620 µm at screening in either eye; any abnormality preventing reliable applanation tonometry of either eye. Systemic: clinically significant abnormalities in laboratory tests at screening; clinically significant systemic diseases; participation in any investigational study within 60 days prior to screening; systemic medication that could have had a substantial effect on IOP within 30 days prior to screening, or anticipated to be used during the study; women of child‐bearing potential who were pregnant, breast‐feeding, planning a pregnancy or not using a medically acceptable form of birth control Pretreatment characteristics between groups: baseline demographics similar across the 3 treatment arms (Table 1 of Walters 2019 (MERCURY‐2)) Other description of the overall study population at baseline: 91.3% of participants completed 3 months of treatment (netarsudil: 90.2%, latanoprost: 89.4%, netarsudil/latanoprost: 94.4%)
Interventions	Netarsudil 0.02%, once per day (p.m.) Latanoprost 0.005%, once per day (p.m.) Netarsudil 0.02%/latanoprost 0.005% (FDC), once per day (p.m.)
Outcomes	Primary outcome reported (time points assessed and reported)  Mean IOP at 8 a.m., 10 a.m., and 4 p.m. at week 2, week 6 and month 3 Other outcomes reported (time points assessed and reported) Mean diurnal IOP, mean change and mean percent change from diurnally adjusted (time‐consistent) baseline IOP, and percentages of participants achieving prespecified thresholds for mean, mean change and mean percent change in mean diurnal IOP Ocular and systemic adverse events during the 3‐month treatment period
Identification	Sponsorship source: Aerie Pharmaceuticals Country: USA and Canada Setting: 60 active sites Online trial registration site: ClinicalTrials.gov Trial registration #: NCT02674854 Phase of the trial (phase 2/phase 3/unclear): phase 3 Current publication reported findings from > 1 trial: no Year of publication accepted: 2019 Year of study initiation (participants screening, enrollment and treatment): 2016
Notes	IOP data were extracted from ClinicalTrials.gov

BB: beta‐blocker; BCVA: best‐corrected visual acuity; CC: complete case; ETDRS: Early Treatment Diabetic Retinopathy Study; FDC: fixed‐dose compound; IOP: intraocular pressure; ITT: intention to treat; mITT: modified intention to treat; OAG: open‐angle glaucoma; OHT: ocular hypertension; PA: prostaglandin analog; POAG: primary open‐angle glaucoma; PP: per protocol; PT: per treatment; ROKi: Rho kinase inhibitor; SD: standard deviation.