Efficacy and Safety of BRIMOCHOL PF and CARBACHOL PF in Chinese Presbyopia Patients

Phase 2

Recruiting

• Conditions: Presbyopia
• Interventions: Drug: BRIMOCHOL PF eye drops; CARBACHOL PF eye drops; Brimonidine eye drops; Placebo

• Registration Number: NCT06948357
• Lead Sponsor: Zhaoke (Guangzhou) Ophthalmology Pharmaceutical Ltd.

Brief Summary

A multicenter, randomized, double-Blind, crossover, placebo-controlled Phase II clinical Study to evaluate the efficacy and safety of BRIMOCHOL PF and CARBACHOL PF in the treatment of Chinese patients with presbyopia.

Detailed Description

119 subjects were planned to be enrolled in this study and randomly assigned in equal proportions into 7 treatment sequences. Each subject will receive a total of 7 treatments, each treatment period will be 1 day, and two adjacent visits during the treatment period need to be eluted for at least 3 days。

The study period included the screening period (Day 14\~Day 1) with 1 visit and the treatment period (Day 0\~Day 30) with 7 visits. There were a total of 8 visits in this study, with a duration of 32 to 45 days.

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-03-06
• Study Start: 2025-03-24
• Study First Submitted QC: 2025-04-23
• Last Update Submitted: 2025-04-23
• Study First Posted: 2025-04-29
• Last Update Posted: 2025-04-29
• Primary Completion: 2025-09-30
• Study Completion: 2025-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 119

Inclusion Criteria

1. At Visit 1 (Screening Period), the age ranges from 45 to 75 years old, regardless of gender

2. At Visit 1 (Screening Period), the corrected distance visual acuity of either eye is ≥ 0.8 (National Standard Logarithmic Visual Acuity Scale,decimal visual acuity) in the clinical routine manifest refraction (distance vision).

3. At Visit 1 (Screening Period), the manifest refraction (distance vision under mesopic conditions) results are as follows: For any eye,-4.00D ≤ equivalent spherical lens power ≤ +2.00D, and the negative cylinder lens power is ≥-2.00D;

4. At least one eye meeting the following at both Visit 1 and Visit 2:

   1. Under mesopic conditions, monocular corrected near visual acuity (MCNVA) ≤65 ETDRS letters (equivalent to decimal visual acuity 0.4) ;
   2. Under mesopic conditions, monocular corrected near visual acuity with a multiple-pinhole occluder (MCNVA_P) improves by ≥15 ETDRS letters compared to monocular corrected near visual acuity without the occluder (MCNVA).

5. During Visit 1 (Screening Period) and Visit 2, both eyes must meet the following criteria:under mesopic conditions, binocular corrected near visual acuity (BCNVA) is ≤65 ETDRS letters (equivalent to decimal visual acuity 0.4);

6. Any eye is phakic or implanted with a monofocal intraocular lens (IOL);

7. Normal iris and pupillary morphology in any eye, with normal light reflex and an interocular pupillary diameter difference ≤1 mm during screening;

Exclusion Criteria

1. Use of corneal or scleral contact lenses within 28 days prior to screening or planned for the duration of the study;
2. Narrow anterior chamber angle (Van Herick grade ≤2 via slit lamp examination) or previous iridotomy or resection in either eye；
3. Ocular history in any eye: hyphema, ciliary body detachment, iridodonesis, or ocular trauma；
4. Any eye with a corneal abnormality that, in the judgment of the investigator, affects visual acuity or intraocular pressure measurements, including moderate to severe dry eye (e.g., significant signs of ocular surface damage (≥5 corneal fluorescein staining spots) on slit lamp microscopy);
5. Any phakic eye has a history of lens tremor, subluxation, or suspected zonular laxity; or any pseudophakic eye has undergone posterior capsulotomy or uses multifocal or extended depth of focus intraocular lenses.
6. Any eye with an axial length of ≥26mm;
7. Either eye has undergone intraocular or corneal surgery (only non-complicated cataract surgery with a monofocal lens placed in the capsular bag more than 6 months after the date of surgery is permitted; complicated cataract surgery is defined as surgery that has resulted in a rupture of the capsule or placement of an IOL outside the capsule (ciliary sulcus, scleral or iris fixation, anterior chamber, etc.));
8. Either eye has a history of congenital or traumatic cataract, congenital aphakia, or opacities in the refractive media that affect visual acuity in the visual axis area.
9. History of uveitis, low intraocular pressure (IOP < 9 mmHg), glaucoma or hypertension (IOP > 21 mmHg) or pseudoexfoliation syndrome in either eye;
10. Active ocular or periocular infection or inflammation in either eye, or a history of recurrent infection or chronic infection (e.g., herpes virus infection) in either eye;
11. Either eye has a history of retinal diseases (such as retinal detachment, age-related macular degeneration, diabetic retinopathy, peripheral retinal diseases that increase the risk of the subject as judged by the investigator) or optic nerve abnormalities.
12. During the screening period, any eye has any ocular disease other than presbyopia that requires treatment with ocular preparations, intravitreal injection or ocular surgery during the study period (except artificial tears, which can be used on the day of ocular examination during the screening period and on non-treatment visits).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment Sequences 1	BRIMOCHOL PF eye drops; CARBACHOL PF eye drops; Brimonidine eye drops; Placebo	BRIMOCHOL PF eye drops and placebo eye drops given once respectively in visit 2; CARBACHOL PF eye drops and placebo eye drops given once respectively in visit 3; Brimonidine eye drops and placebo eye drops given once respectively in visit 4; BRIMOCHOL PF eye drops given twice in visit 5; CARBACHOL PF eye drops given twice in visit 6; Brimonidine eye drops given twice in visit 7; Placebo eye drops given twice in visit 8.
Treatment Sequences 2	BRIMOCHOL PF eye drops; CARBACHOL PF eye drops; Brimonidine eye drops; Placebo	Placebo eye drops given twice in visit 2; BRIMOCHOL PF eye drops and placebo eye drops given once respectively in visit 3; CARBACHOL PF eye drops and placebo eye drops given once respectively in visit 4; Brimonidine eye drops and placebo eye drops given once respectively in visit 5; BRIMOCHOL PF eye drops given twice in visit 6; CARBACHOL PF eye drops given twice in visit 7; Brimonidine eye drops given twice in visit8.
Treatment Sequences 3	BRIMOCHOL PF eye drops; CARBACHOL PF eye drops; Brimonidine eye drops; Placebo	Brimonidine eye drops given twice in visit 2; Placebo eye drops given twice in visit 3; BRIMOCHOL PF eye drops and placebo eye drops given once respectively in visit 4; CARBACHOL PF eye drops and placebo eye drops given once respectively in visit 5; Brimonidine eye drops and placebo eye drops given once respectively in visit 6; BRIMOCHOL PF eye drops given twice in visit 7; CARBACHOL PF eye drops given twice in visit 8.
Treatment Sequences 6	BRIMOCHOL PF eye drops; CARBACHOL PF eye drops; Brimonidine eye drops; Placebo	Brimonidine eye drops and placebo eye drops given once respectively in visit 2; BRIMOCHOL PF eye drops given twice in visit 3; CARBACHOL PF eye drops given twice in visit 4; Brimonidine eye drops given twice in visit 5; Placebo eye drops given twice in visit 6; BRIMOCHOL PF eye drops and placebo eye drops given once respectively in visit 7; CARBACHOL PF eye drops and placebo eye drops given once respectively in visit 8.
Treatment Sequences 4	BRIMOCHOL PF eye drops; CARBACHOL PF eye drops; Brimonidine eye drops; Placebo	CARBACHOL PF eye drops given twice in visit 2; Brimonidine eye drops given twice in visit 3; Placebo eye drops given twice in visit 4; BRIMOCHOL PF eye drops and placebo eye drops given once respectively in visit 5; CARBACHOL PF eye drops and placebo eye drops given once respectively in visit 6; Brimonidine eye drops and placebo eye drops given once respectively in visit 7; BRIMOCHOL PF eye drops given twice in visit 8.
Treatment Sequences 5	BRIMOCHOL PF eye drops; CARBACHOL PF eye drops; Brimonidine eye drops; Placebo	BRIMOCHOL PF eye drops given twice in visit 2; CARBACHOL PF eye drops given twice in visit 3; Brimonidine eye drops given twice in visit 4; Placebo eye drops given twice in visit 5; BRIMOCHOL PF eye drops and placebo eye drops given once respectively in visit 6; CARBACHOL PF eye drops and placebo eye drops given once respectively in visit 7; Brimonidine eye drops and placebo eye drops given once respectively in visit 8.
Treatment Sequences 7	BRIMOCHOL PF eye drops; CARBACHOL PF eye drops; Brimonidine eye drops; Placebo	CARBACHOL PF eye drops and placebo eye drops given once respectively in visit 2; Brimonidine eye drops and placebo eye drops given once respectively in visit 3; BRIMOCHOL PF eye drops given twice in visit 4; CARBACHOL PF eye drops given twice in visit 5; Brimonidine eye drops given twice in visit 6; Placebo eye drops given twice in visit 7; BRIMOCHOL PF eye drops and placebo eye drops given once respectively in visit 8.

Primary Outcome Measures

Name	Time	Method
Changes in MCNVA(monocular corrected near visual acuity) ETDRS letters and MCDVA (monocular corrected distance visual acuity) ETDRS letters from baseline in the study eyes after administration	15minutes, 1hour, 2hour, 4hour15minutes, 6hour, and 8hour after administration	In the mesopic condition, the proportion of subjects whose MCNVA in the study eye increased by ≥15 ETDRS letters and whose MCDVA in the study eye did not decrease by ≥5 ETDRS letters from the pre-dose baseline at 15minutes, 1hour, 2hour, 4hour15minutes, 6hour, and 8hour after dosing.

Secondary Outcome Measures

Name	Time	Method
Changes in MCNVA(monocular corrected near visual acuity) ETDRS letters from baseline in the study eyes after administration	15 minutes to 8 hours after administration	The weighted mean of the area under the curve (AUC) for the increase in MCNVA ETDRS letter gain from baseline under mesopic conditions in the study eye across post-dose evaluation intervals (15 minutes through 8 hours).
Changes in BCNVA (Binocular Corrected Near Visual Acuity) ETDRS letters and BCDVA (Binocular Corrected Distance Visual Acuity) ETDRS letters from baseline after administration	15minutes, 1hour, 2hour, 4hour15minutes, 6hour, and 8hour after administration	1. In the mesopic condition, the proportion of subjects whose BCNVA increased by ≥15 ETDRS letters and whose BCDVA did not decrease by ≥5 ETDRS letters from the pre-dose baseline at 15minutes, 1hour, 2hour, 4hour15minutes, 6hour, and 8hour after dosing.; 2. In the mesopic condition, the proportion of subjects whose BCNVA increased by ≥10 ETDRS letters and whose BCDVA did not decrease by ≥5 ETDRS letters from the pre-dose baseline at 15minutes, 1hour, 2hour, 4hour15minutes, 6hour, and 8hour after dosing.; 3. In the mesopic conditions, the proportion of subjects whose BCNVA increased by ≥ 15 ETDRS letters across all post-dose evaluation intervals (15minutes through 8hour).; 4. In the mesopic conditions, the proportion of subjects whose BCNVA increased by ≥ 10 ETDRS letters across all post-dose evaluation intervals (15minutes through 8hour).
Changes in pupil diameter from baseline after administration	15minutes, 1hour, 2hour, 4hour15minutes, 6hour, and 8hour after administration	Quantitative changes in pupil diameter (measured in study eye and binocular average) from pre-dose baseline values under mesopic conditions at 15minutes, 1hour, 2hour, 4hour15minutes, 6hour, and 8hour after administration.

Trial Locations

Locations (1)

Optometry Hospital of Wenzhou Medical University; 🇨🇳 Wenzhou, Zhejiang, China