Non-Inferiority Trial of Brinzolamide-Timolol Versus Azarga in Reducing Intraocular Pressure in Open-Angle Glaucoma and Ocular Hypertension

The primary objective of this clinical trial is to confirm the **clinical non-inferiority** of a new generic fixed combination of Brinzolamide 10mg/ml + Timolol 5mg/ml eye drops compared to the reference product Azarga® 10mg/ml + 5mg/ml eye drops. This is evaluated in patients with elevated intraocular pressure, specifically those diagnosed with open angle glaucoma or ocular hypertension. The clinical relevance of this objective lies in its potential to provide an alternative treatment option that is equally effective in managing intraocular pressure, which is crucial in preventing optic nerve damage and preserving vision in affected patients.

Secondary objectives include:

• Comparing the overall efficacy and safety of the two combined brinzolamide/timolol products (test and reference) in subjects with ocular hypertension or open angle glaucoma.

The clinical trial involves participants diagnosed with **ocular hypertension** or **glaucoma**, specifically open-angle glaucoma, including cases with pseudoexfoliation or pigment dispersion. The study population comprises both male and female subjects, aged 18 years and older, of any race. Participants are required to have a best-corrected visual acuity of at least 20/100, corresponding to logMAR ≤ 0.7 in both eyes. The trial does not include a vulnerable population. Participants must be able to safely discontinue all ocular hypotensive medications and undergo an appropriate washout period. Females of reproductive age must practice effective birth control methods if sexually active. The sponsor has not provided information regarding the total number of participants. The selection criteria ensure that participants can understand the trial requirements, agree to follow-up visits, and provide informed consent. The trial aims to assess the clinical non-inferiority of a new generic fixed combination of Brinzolamide and Timolol eye drops compared to the reference product Azarga® in managing elevated intraocular pressure.

The clinical trial is designed as a **randomized**, observer-blind, active-reference, two-arm, parallel group, multi-center study. The primary objective is to confirm the clinical non-inferiority of a new generic fixed combination of **brinzolamide** 10mg/ml and **timolol** 5mg/ml eye drops compared to the reference product Azarga® 10mg/ml + 5mg/ml eye drops in patients with elevated intraocular pressure due to open angle **glaucoma** or **ocular hypertension**. The trial will assess the average change in diurnal intraocular pressure (IOP) from baseline to the end of the study, comparing the two study arms. The trial is expected to commence recruitment on March 1, 2024, and conclude by June 30, 2025.

Participants will be involved in the study for a maximum treatment period of 87 days. The study includes several key visits: an initial screening visit to confirm eligibility, followed by visits at weeks 2, 6, and 12 to monitor IOP changes and assess the primary and secondary endpoints. The primary endpoint is the difference in mean diurnal IOP change from baseline to the week 12 visit. Secondary endpoints include IOP changes at weeks 2 and 6, and the frequency of adverse events related to the study drugs. The end-of-study visit will occur at week 12, marking the completion of the participant's involvement.

Participants are expected to adhere to the study protocol, including the discontinuation of any ocular hypotensive medications prior to the trial and compliance with the washout period. The inclusion criteria require participants to be adults aged 18 years or older, diagnosed with unilateral or bilateral open angle glaucoma or ocular hypertension, and able to provide informed consent. Conditions for early termination from the study include non-compliance with the study protocol, withdrawal of consent, or any adverse event that, in the investigator's opinion, warrants discontinuation for the safety of the participant.

The clinical trial involves the administration of two **eye drop** formulations, both containing the active substances **brinzolamide** and **timolol**. The experimental medication, referred to as the test product, is a generic fixed combination of Brinzolamide 10 mg/mL and Timolol 5 mg/mL, marketed under the name "Brinzolamide-Timolol" by OMNIVISION GMBH. This formulation is presented as an eye drops suspension and is administered via the **eye/ear/nose drops** route. The dosage regimen for this product is up to 4 drops per day, with a maximum total dose of 348 drops over a treatment period of 87 days. The pharmaceutical form is specifically designed for ocular use, and the active substances are of chemical origin.

The comparator treatment in this study is the reference product "AZARGA 10 mg/mL + 5 mg/mL eye drops, suspension," manufactured by NOVARTIS EUROPHARM LIMITED. This product also contains the active substances brinzolamide and timolol, formulated as an eye drops suspension. The administration route is identical to the test product, utilizing the eye/ear/nose drops method. The dosage and treatment period for AZARGA are consistent with the test product, allowing for a direct comparison of efficacy and tolerability. Both products are not pediatric formulations and are intended for use in patients with elevated intraocular pressure due to open-angle glaucoma or ocular hypertension.

Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The trial aims to establish the non-inferiority of the generic formulation compared to the reference product by evaluating changes in diurnal intraocular pressure from baseline to the end of the study. The study design is a randomized, observer-blind, active-reference, two-arm, parallel group, multi-center clinical trial.

Efficacy in this clinical trial will be assessed by evaluating the change in **intraocular pressure (IOP)** in patients with open angle glaucoma or ocular hypertension. The primary efficacy endpoint is the difference in mean diurnal IOP change from baseline to the week 12 visit, after adjusting for baseline measurements. Secondary endpoints include the difference in mean diurnal IOP change from baseline to week 2 and week 6 visits, also adjusted for baseline measurements, as well as the frequency of study drug-related adverse events.

Measurements of IOP will be conducted at specified timepoints: baseline (week 0), week 2, week 6, and week 12. The trial is designed to compare the efficacy of a generic fixed combination of Brinzolamide 10 mg/mL and Timolol 5 mg/mL eye drops against the reference product, Azarga® 10 mg/mL + 5 mg/mL eye drops. The study employs a randomized, observer-blind, active-reference, two-arm, parallel group, multi-center design to ensure robust and unbiased results.