CTRI/2020/01/022619.

Methods	Randomized, parallel group, active controlled trial  Method of generating randomization sequence: computer‐generated randomization Method of allocation concealment: sequentially numbered, sealed, opaque envelopes Masking: participant and investigator (double‐masked)
Participants	Inclusion criteria: men and women aged 18–65 years; newly diagnosed primary open‐angle glaucoma/ocular hypertension in 1 or both eyes confirmed by Goldmann applanation tonometry; IOP 22–27 mmHg at time of screening in any 1 eye. In case both the eyes of a single subject are affected then the eye fulfilling the criteria will be considered for the evaluations. If both eyes are fulfilling the criteria, then the right eye will be considered for the study; visual acuity ≥ 6/60; willingness to give written informed consent prior to participation in trial Exclusion criteria: any of the following. Ophthalmic: any severe or advanced cases of glaucoma; Shaffer angle grade ≤ 2 in either eye, as measured by gonioscopy; with pseudoexfoliation or pigment dispersion component glaucoma; blind or have 1 eye; severe central visual field loss in either eye measured by perimetry; cup–disk ratio > 0.80; current or history within 3 months prior to baseline of significant ocular disease, e.g. corneal edema, uveitis, ocular infection or ocular trauma in either eye; current corneal abnormalities that would prevent accurate IOP readings with the Goldmann applanation tonometer; history of any ocular surgery in either eye (e.g. peripheral iridotomy, glaucoma incisional or laser surgery, refractive surgery) or are planning to undergo any ocular surgery during the study period; central corneal thickness > 600 mm in either eye; history of clinically relevant or progressive retinal disease such as retinal degeneration, diabetic retinopathy or retinal detachment; contact lens user; contraindication or hypersensitivity to any component of study medication; history of chronic use of any ocular medication; local administration of corticosteroids injections in the eye.  Others: use within 1 month prior to baseline of systemic corticosteroid or high‐dose salicylate therapy or oral carbonic anhydrase inhibitor; pregnant, breast‐feeding or planning a pregnancy; of child‐bearing potential who do not agree to utilize an adequate form of birth control; history of CVS, hepatic, psychiatric, cancer or renal diseases that could be considered significant for enrollment in the study; history of bronchial asthma, bronchial hyper‐reactivity or severe COPD that would preclude the safe administration of a topical beta‐blocker; people receiving high‐dose (> 1 g per day) salicylate, topical as well as oral beta‐blockers, alpha agonists and blockers, angiotensin‐converting enzyme inhibitors and calcium channel blockers, systemic administration of corticosteroids or immunosuppressive agents; participation in any clinical study within 30 days prior to entry into the study; unwilling to comply with the study protocol and does not provide written informed consent to participation; with type 1 and uncontrolled type 2 diabetes mellitus (i.e. defined as glycosylated hemoglobin > 7%)
Interventions	Netarsudil ophthalmic solution 0.02% w/v: 1 drop in affected eye twice per day for 90 days Timolol maleate eye drops 0.5% w/v: 1 drop in affected eye twice per day for 90 days
Outcomes	Primary outcome Mean reduction in IOP at end of 12 weeks of treatment compared to baseline at 9 a.m., 11 a.m. and 5 p.m.; time point: day 0 and day 84 Secondary outcomes Mean reduction in IOP at end of 4 weeks of treatment compared to baseline; mean reduction in IOP at end of 8 weeks of treatment compared to baseline; assessment of safety (comparison of incidence of treatment‐emergent adverse event) and change in ophthalmological parameters; assessment of tolerability of investigational product based on incidence of adverse events and serious adverse events; changes in laboratory values; time point: days 0, 28 and 56
Notes	Phase 3