Study design and patients
ocular disease, inflammation, Diabetic Retinopathy, ocular infection, ocular trauma, keratitis, psychiatric, coma, occludable, glaucoma, Glaucoma, blepharitis, ocular hypotensive, angle-closure glaucoma, hypersensitivity, pseudoexfoliation
SYSTEMIC DISEASE, DIABETIC RETINOPATHY, DRY EYE, KERATITIS, BLEPHARITIS, COMA, CONJUNCTIVITIS, GLAUCOMA, ANGLE-CLOSURE GLAUCOMA, HYPERSENSITIVITY, GLAUCOMA, HERPES SIMPLEX
MERCURY-3 (NCT03284853) was a 6-month prospective, double-masked, randomized, multicenter, active-controlled, parallel-group, non-inferiority study. Participants were evaluated at one of 58 clinical sites in 11 European countries (Supplementary Table The study was conducted in accordance with the Declaration of Helsinki, US FDA law, EU Clinical Trials Directive 2001/20/ED and in compliance with international guidelines (ICHGCP E6R2). Local and national regulatory requirements were followed as appropriate, and participants gave informed, written consent prior to entering the study.Eligible participants were aged ≥ 18 years and had a diagnosis of OAG or OHT in both eyes that was insufficiently controlled by their existing treatment (medicated IOP ≥ 17 mmHg in at least one eye and < 28 mmHg in both eyes at screening). To qualify for the study, patients had to have been taking the same IOP-lowering medication for 30 days prior to screening. Between screening and the first treatment visit, a washout period was required (4 weeks for PGAs and β-adrenoceptor antagonists; 2 weeks for adrenergic agonists [including α-agonists such as brimonidine and apraclonidine]; and 5 days for muscarinic agonists [e.g., pilocarpine] and carbonic anhydrase inhibitors). Lid scrubs (which may have been used prior to, but not after, screening) and lubricating drops for dry eye (unrestricted use) were permitted.The best-corrected visual acuity requirement was + 1.0 logarithm of the minimum angle resolvable (logMAR) or better by Early Treatment Diabetic Retinopathy Study (ETDRS) criteria in each eye (equivalent to 20/200 or better Snellen visual acuity in each eye). Before starting the masked study medication, the patients needed, as appropriate, a negative pregnancy test and/or willingness to use highly effective contraception during the study.Treatment-naïve patients were excluded, as were those who were participating in any investigational study within 30 days prior to screening and those considered vulnerable (such as minors or adults under legal protection) or unable to express their consent (e.g., hospitalized persons in coma), persons deprived of liberty (prisoners from jails), or persons subject to psychiatric care. Ophthalmic exclusion criteria were as follows: clinically significant ocular disease; pseudoexfoliation or pigment dispersion glaucoma; a history of angle-closure glaucoma or eyes with complete or partial angle closure, and occludable anterior chamber angle (Shaffer grade < 2); previous laser peripheral iridotomy and/or an IOP ≥ 36.0 mmHg (unmedicated) in either eye. Medication-based exclusion criteria were: current (immediately prior to screening visit) treatment with BIM/TIM; use of more than two ocular hypotensive medications within 30 days of screening; and known hypersensitivity or contraindication to any component of the study medications or fluorescein. Any use of any topical steroid medication on the face or in, or around, the eyes was not permitted during the study, and use of steroid at screening was an exclusion criterion. Patients with prior insufficient IOP response/treatment failure (i.e., IOP did not reach the target range) with BIM/TIM ophthalmic solution were excluded. Glaucoma intraocular surgery (including laser treatments) as well as refractive surgery or ocular trauma in the six months prior to screening, and any other ocular surgery within three months prior to screening were also exclusion criteria.Further exclusion criteria were a mean central corneal thickness > 620 µm at screening; any abnormality preventing reliable Goldmann applanation tonometry in either eye; recent or current evidence of ocular infection or inflammation, clinically significant blepharitis, conjunctivitis, herpes simplex, and/or keratitis. Patients were excluded if laboratory tests identified clinically significant abnormalities or previously unknown systemic disease deemed likely to interfere with the study. The use of any systemic medication, including corticosteroid use, with a possible effect on IOP was also an exclusion criterion.