A Non-Inferiority Study Comparing Brimonidine Tartrate and Timolol Fixed-Dose Combination Eye Drops to an Active Comparator in Patients with Open-Angle Glaucoma or Ocular Hypertension
- Trial ID
- 2025-523227-22-00
- Protocol
- BECRO/OV/BRIMOTIM
- Sponsor
- OmniVision GmbH
Trial statistics
Objectives
The primary objective is to establish the clinical non-inferiority of a generic phosphate-free, preservative-free fixed-dose combination of brimonidine tartrate 2 mg/ml and timolol 5 mg/ml eye drops compared to Combigan® 2 mg/ml + 5 mg/ml. Evaluation is based on the mean change in diurnal intraocular pressure from baseline to the end of the study in patients diagnosed with open-angle glaucoma or ocular hypertension.
- Comparison of overall efficacy and safety between the test product and the comparator.
Participants
The sponsor did not provide information regarding the total number of participants. The study population consists of male and female patients with open-angle glaucoma or ocular hypertension. Eligible participants are aged 18 years or older. Inclusion criteria require an average intraocular pressure between 22 mm Hg and 34 mm Hg at baseline and a best-corrected visual acuity of Snellen 20/100 or logMAR ≤ 0.7 in the study eye. Participants must not have used intraocular pressure-lowering drugs for at least 4 weeks prior to the study. Additional requirements include controlled arterial blood pressure and the absence of optic nerve damage or visual field loss progression. Females of reproductive age must utilize effective contraception.
Plans and Procedures
This non-inferiority, randomized, observer-blind, active-comparator, two-arm, parallel group clinical trial is designed to compare the efficacy and tolerability of a generic fixed-dose combination of brimonidine tartrate and timolol eye drops against Combigan in patients with open-angle glaucoma or ocular hypertension. The study methodology aims to evaluate the mean change in diurnal intraocular pressure from baseline to the end of the study. The trial involves a screening visit to assess eligibility based on specific criteria, including age, diagnosis, and baseline pressure measurements. Following screening, participants are assigned to either the test or comparator arm. The primary efficacy endpoint is measured at the week 12 visit, with secondary endpoints evaluating changes at week 2 and week 6, alongside the frequency of adverse events. The total duration of participant involvement extends through the final study visit at week 12.
Treatment
The experimental medication consists of a generic fixed-dose combination of brimonidine tartrate 2 mg/ml and timolol 5 mg/ml. This therapeutic agent is administered as an ocular solution in the form of eye drops. The prescribed dosage is 4 gtt (drops) to be administered via the ocular route.
The comparator treatment is Combigan, which contains timolol maleate 2 mg/ml and brimonidine tartrate 5 mg/ml. This product is provided as an ocular solution in the form of eye drops. The administration dose is 4 gtt per application.
This study is designed to evaluate the efficacy and tolerability of the test product in patients with open-angle glaucoma or ocular hypertension by measuring changes in intraocular pressure. The clinical trial follows a non-inferiority design to compare the generic combination against the active comparator.
Efficacy
The primary efficacy endpoint is defined as the difference between the test product and the comparator in the mean change of diurnal intraocular pressure from baseline to the week 12 visit, after adjusting for baseline measurements at week 0. This assessment aims to evaluate the clinical non-inferiority of the generic fixed dose combination in patients with open-angle glaucoma or ocular hypertension.
Secondary efficacy parameters include the difference between the test and comparator products in the mean diurnal intraocular pressure change from baseline to the week 2 and week 6 visits, following adjustment for baseline measurements at week 0.
Inclusion and Exclusion Criteria
Inclusion Criteria
- male or female, of any race and ≥18 years of age
- diagnosed of unilateral or bilateral open angle glaucoma (including open-angle glaucoma with pseudoexfoliation or pigment dispersion) or ocular hypertension
- average IOP ≥ 22 mm Hg and ≤ 34 mm Hg measured at 08:00 am, 12:00 am and 04:00 pm pre-treatment at baseline in at least one eye
- without treatment for open-angle glaucoma with IOP-lowering drugs, for at least 4 weeks
- best-corrected visual acuity ≥20 of 100 (Snellen) corresponding to logMAR ≤ 0.7 in the study eye
- females who participate in the study are either unable to gestate [i.e. post-menopausal (absence of menses for 12 months prior to drug administration), hysterectomy, bilateral oophorectomy, tubal ligation at least 6 months prior to drug administration] or at reproductive age; Females of reproductive age if sexually active, must be practicing an effective method of birth control throughout the study; reliable contraception methods are considered the following: • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal or transdermal • progestogen-only hormonal contraception associated with inhibition of ovulation oral, implantable or injectable • intrauterine device (IUD) • intrauterine hormone-releasing system (IUS) • bilateral tubal occlusion • vasectomised partner • sexual abstinence
- expected by the investigator that IOP will remain controlled under treatment without optic nerve damage or progression of visual field loss
- patients with controlled arterial blood pressure according to the investigator’s opinion
- able to understand the requirements of the clinical trial and to agree to return for the required follow-up visits
- willing to provide voluntarily written informed consent and data protection declaration before any clinical trial related procedure is performed
Exclusion Criteria
- history of chronic or recurrent inflammatory eye disease (i.e. scleritis, uveitis, herpes keratitis), ocular trauma within the past 6 months or ocular inflammation within the past 3 months or infections
- severe central visual field loss (i.e., sensitivity ≤10 decibel [dB] in at least 2 of the 4 visual field test points closest to the point of fixation) in either eye
- treatment with local or systemic corticosteroids in non-stable doses in the last 30 days
- treatment with oral carbonic anhydrase inhibitors (e.g., acetazolamide, methazolamide, topiramate, sultiame, zonisamide)
- ocular treatment with any prostamide, prostaglandin, carbonic anhydrase inhibitor and pilocarpine
- current use of topical, ocular, nonsteroidal anti-inflammatory drugs
- any change in any systemic medication that could affect IOP within the last 30 days before the beginning of and during the study (e.g., clonidine, β-blockers etc.)
- known hypersensitivity to beta-blockers
- a history of allergic hypersensitivity or poor tolerance to any component of the eye drops used in this clinical trial
- a history of, or current other severe ocular pathology (including severe dry eye) in either eye, that would preclude the administration of a beta-blocker
- a history of depression, cerebral or coronary insufficiency, Raynaud's phenomenon, orthostatic hypotension or thromboangiitis obliterans
- any uncontrolled systemic disease
- current reactive airway disease including bronchial asthma or a history of bronchial asthma, or severe chronic obstructive pulmonary disease
- severe acute allergic rhinitis
- sinus bradycardia, sick sinus syndrome, sino-atrial block, second- or third-degree atrioventricular block not controlled with pace-maker
- overt cardiac failure, cardiogenic shock
- use at any time prior to baseline of intraocular corticosteroid implant
- use within two weeks prior to baseline of: 1) topical ophthalmic corticosteroid, or 2) topical corticosteroid
- use within one month prior to baseline of: 1) systemic corticosteroid, 2) monoamine oxidase (MAO) inhibitor therapy, 3) any antidepressant which affects noradrenergic transmission (e.g., tricylic antidepressants, mianserin) or 4) adrenergic-augmenting psychotropic drug (e.g., desipramine, amitriptyline)
- use within six months prior to baseline of intravitreal or subtenon injection of ophthalmic corticosteroid
- underwent within twelve months prior to baseline: refractive surgery, filtering surgery or laser surgery for IOP reduction
- pregnancy or breast-feeding or childbearing potential not protected by a highly effective contraceptive method of birth control
- narrow-angle/angle-closure glaucoma
- current participation or not yet completed period of at least 30 days since ending of another investigational device or drug trial(s)
- unwillingness or inability to comply with the clinical trial procedures
- severe illness or other condition that would make the patient, in the opinion of the Investigator, unsuitable for the study
- unwillingness to consent to storage, saving and transmission of pseudonymous medical data for clinical trial reasons
- who are legally incapacitated
- who are legally detained in an official institute
- compromised cornea or corneal abnormalities that will preclude accurate IOP-reading with an applanation tonometer
- clinically significant or progressive retinal disease (e.g. retinal degeneration, diabetic retinopathy, retinal detachment) in either eye
- intraocular surgery within the past 3 months
- ocular laser surgery within the past 1 month
- planned ocular surgery of any kind during study participation
- extremely narrow or partially closed angle, cup/disk ratio >0.8
- a history of, or current severe hepatic or renal impairment
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Greece | Not Yet Recruiting | 01 May 2026 | 180 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Brimonidine-Timolol | Test | EYE DROPS, SOLUTION | OCULAR | 4 | 89 | PRD12928113 |
Combigan, 2 mg/ml + 5 mg/ml, krople do oczu, roztwór | Comparator | KROPLE DO OCZU, ROZTWÓR | OCULAR | 4 | 89 | PRD10031367 |