Evaluation of Atropine Sulfate Monohydrate Eye Drops in Myopia Progression in Pediatric Patients: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this clinical trial is to evaluate the difference in **axial eye length (AXL)** over a 12-month application period with 0.02% atropine compared to placebo in children with myopia. This is clinically relevant as it aims to assess the potential of atropine eye drops in slowing the progression of myopia, a condition that can lead to significant visual impairment if left unchecked.

Secondary objectives include:

• Assessing the difference in AXL over a 12-month period with 0.04% atropine versus placebo, and 0.02% versus 0.04% atropine.
• Evaluating the difference in AXL over a 24-month period with 0.02% and 0.04% atropine versus placebo and between the two concentrations.
• Investigating the rebound phenomenon in both active arms (0.02% and 0.04%) during the 24 to 36-month period compared to placebo and between the two concentrations.
• Determining the cycloplegic spherical equivalent refraction (SER) difference for 12 and 24-month administration periods with 0.02% and 0.04% atropine versus placebo and between the two concentrations.
• Measuring the difference in AXL/CR index for 12 and 24-month administration periods with 0.02% and 0.04% atropine versus placebo and between the two concentrations.
• Evaluating visual functional characteristics, including best corrected distance visual acuity (BCDVA), best corrected near visual acuity (BCNVA), contrast sensitivity, and color perception.

The clinical trial focuses on **myopia in children**, specifically targeting a study population aged 6 to 12 years. Both male and female participants are included, with no specific vulnerable populations selected. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on specific ophthalmic criteria, including a diagnosis of myopia with a spherical component of refraction ranging from -0.5 Dsf to -4.75 Dsf and astigmatism between 0 to -2.5 Dcyl in at least one eye. Participants are required to have normal ocular findings and history, excluding the need for spectacle correction and minor eye conditions. Additionally, normal binocular functions and intraocular pressure are prerequisites. The study does not specify any particular lifestyle considerations such as diet or physical activity. Key inclusion criteria involve the willingness of the child and their parents or legal guardians to commit to a two-year period of daily eye drop application, along with regular clinical examinations and diary maintenance over three years.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy, safety, and side effects of highly diluted atropine collyrium in slowing the progression of **myopia** in children. The trial involves three groups: one receiving Atropini collyrium 0.02%, another receiving Atropini collyrium 0.04%, and a placebo group. The primary objective is to assess the difference in axial eye length (AXL) over a 12-month application period with 0.02% atropine versus placebo. Secondary endpoints include comparisons of AXL changes over 12 and 24 months, the rebound phenomenon, and various visual and functional characteristics.

The trial is expected to last until December 31, 2025, with participant recruitment having started on September 1, 2021. Participants will be involved for a period of up to 36 months, with the first 24 months dedicated to the administration of eye drops and the remaining 12 months for observation of any rebound effects. Study visits are structured to include an initial screening visit to confirm eligibility based on criteria such as age (6-12 years), specific refractive errors, and normal ocular health, followed by regular follow-up visits every six months. These visits will monitor the progression of myopia, assess safety, and ensure compliance with the treatment regimen. The end-of-study visit will conclude the participant's involvement, evaluating the long-term effects of the treatment.

Participants may be withdrawn from the study if they experience significant adverse effects, fail to comply with the study protocol, or if the investigator deems it necessary for their safety. The study's methodology ensures rigorous data collection and analysis, maintaining the integrity of the trial's findings. The use of a placebo control and blinding minimizes bias, providing reliable results on the efficacy of atropine collyrium in managing myopia progression in the pediatric population.

The clinical trial involves the administration of **Atropini collyrium 0.04%**, an experimental medication formulated as eye drops. The active substance in this formulation is **atropine sulfate monohydrate**, a chemical compound. The eye drops are intended for **ocular use** and are administered at a concentration of 0.04% (W/W) percent weight/weight. The maximum daily dose is 0.05% (W/W), with a total treatment period not exceeding 24 months. The medication is not specifically formulated for pediatric use, and its role in the trial is as a test product.

Another experimental treatment in the study is **Atropini collyrium 0.02%**, also formulated as eye drops containing **atropine sulfate monohydrate**. This product is similarly administered via the ocular route at a concentration of 0.02% (W/W) percent weight/weight. The maximum daily and total dose is consistent with the 0.04% formulation, set at 0.05% (W/W). The treatment period is also capped at 24 months. This product is intended for use in children, although it is not a pediatric-specific formulation, and serves as a test product in the trial.

The study includes a **Placebo collyrium**, which is also in the form of eye drops. The placebo is designed to mimic the experimental treatments in appearance and administration route, which is ocular. The placebo does not contain the active substance **atropine sulfate monohydrate**. The dosing schedule and treatment period for the placebo are aligned with those of the active treatments, with a maximum daily dose of 0.05% (W/W) and a treatment duration of up to 24 months. The placebo serves as a control to evaluate the efficacy and safety of the atropine formulations.

The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints related to the progression of **myopia** in children. The primary endpoint is the difference in axial eye length (AXL) over a 12-month application period with 0.02% atropine compared to placebo. Secondary endpoints include the difference in AXL over a 12-month period with 0.04% atropine versus placebo, and the difference in AXL over a 24-month period with both 0.02% and 0.04% atropine compared to placebo and each other. Additional secondary endpoints involve the assessment of the rebound phenomenon, cycloplegic spherical equivalent refraction (SER) differences, AXL/CR index differences, visual functional characteristics, and other growth and functional characteristics of the eye.

Measurements will be collected at specified intervals throughout the trial, with a focus on a 12-month and 24-month administration period. The trial will also evaluate the influence of genetic predisposition and lifestyle factors, as well as the intensity, severity, and frequency of side effects. Compliance and quality of life assessments will be conducted, including self-assessment by younger patients and evaluations by parents or legal guardians. The trial is designed to be double-blinded and placebo-controlled, ensuring rigorous assessment of the efficacy of atropine collyrium in slowing the progression of myopia in the pediatric population.