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

A Multicenter, Randomized, Double-Blind, Crossover, Placebo-Controlled Phase II Clinical Study to Evaluate the Efficacy and Safety of BRIMOCHOL PF, CARBACHOL PF in Chinese Patients With Presbyopia

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.

Study Overview

• Status: Recruiting
• Conditions: Presbyopia
• Intervention / Treatment: Drug: BRIMOCHOL PF eye drops; CARBACHOL PF eye drops; Brimonidine eye drops; Placebo

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 Type: Interventional
• Enrollment (Estimated): 119
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Peiqiu Gu; Phone Number: 0577-88075582; Email: EYE_ec@126.com
• Study Contact Backup: Name: Xiaochen Wang

Study Locations

• China
  • Zhejiang
    • Wenzhou, Zhejiang, China
      • Recruiting
      • Optometry Hospital of Wenzhou Medical University
      • Contact: Xiaochen Wang
      • Contact: Peiqiu Gu; Email: EYE_ec@126.com
      • Principal Investigator: Jia Qu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Sequences 1; 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.	Drug: BRIMOCHOL PF eye drops; CARBACHOL PF eye drops; Brimonidine eye drops; Placebo; BRIMOCHOL PF eye drops, CARBACHOL PF eye drops, Brimonidine eye drops and Placebo were administered in 7 treatment sequences in various combinations and doses
Experimental: Treatment Sequences 2; 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.	Drug: BRIMOCHOL PF eye drops; CARBACHOL PF eye drops; Brimonidine eye drops; Placebo; BRIMOCHOL PF eye drops, CARBACHOL PF eye drops, Brimonidine eye drops and Placebo were administered in 7 treatment sequences in various combinations and doses
Experimental: Treatment Sequences 3; 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.	Drug: BRIMOCHOL PF eye drops; CARBACHOL PF eye drops; Brimonidine eye drops; Placebo; BRIMOCHOL PF eye drops, CARBACHOL PF eye drops, Brimonidine eye drops and Placebo were administered in 7 treatment sequences in various combinations and doses
Experimental: Treatment Sequences 4; 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.	Drug: BRIMOCHOL PF eye drops; CARBACHOL PF eye drops; Brimonidine eye drops; Placebo; BRIMOCHOL PF eye drops, CARBACHOL PF eye drops, Brimonidine eye drops and Placebo were administered in 7 treatment sequences in various combinations and doses
Experimental: Treatment Sequences 5; 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.	Drug: BRIMOCHOL PF eye drops; CARBACHOL PF eye drops; Brimonidine eye drops; Placebo; BRIMOCHOL PF eye drops, CARBACHOL PF eye drops, Brimonidine eye drops and Placebo were administered in 7 treatment sequences in various combinations and doses
Experimental: Treatment Sequences 6; 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.	Drug: BRIMOCHOL PF eye drops; CARBACHOL PF eye drops; Brimonidine eye drops; Placebo; BRIMOCHOL PF eye drops, CARBACHOL PF eye drops, Brimonidine eye drops and Placebo were administered in 7 treatment sequences in various combinations and doses
Experimental: Treatment Sequences 7; 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.	Drug: BRIMOCHOL PF eye drops; CARBACHOL PF eye drops; Brimonidine eye drops; Placebo; BRIMOCHOL PF eye drops, CARBACHOL PF eye drops, Brimonidine eye drops and Placebo were administered in 7 treatment sequences in various combinations and doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	15minutes, 1hour, 2hour, 4hour15minutes, 6hour, and 8hour after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in MCNVA(monocular corrected near visual acuity) ETDRS letters from baseline in the study eyes after administration	In the mesopic conditions, the proportion of subjects whose MCNVA in the study eye increased by ≥ 10 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.; In the mesopic conditions, the proportion of subjects whose MCNVA in the study eye increased by ≥ 15 ETDRS letters from the pre-dose baseline at 15minutes, 1hour, 2hour, 4hour15minutes, 6hour, and 8hour after dosing.; In the mesopic conditions, the proportion of subjects whose MCNVA in the study eye increased by ≥ 10 ETDRS letters from the pre-dose baseline at 15minutes, 1hour, 2hour, 4hour15minutes, 6hour, and 8hour after dosing.	15minutes, 1hour, 2hour, 4hour15minutes, 6hour, and 8hour after administration
Changes in MCNVA(monocular corrected near visual acuity) ETDRS letters from baseline in the study eyes after administration	Mean ETDRS letter gain in study eye MCNVA compared to the baseline measurements under mesopic conditions across all post-dose evaluation intervals (15 minutes through 8 hours).	15 minutes to 8 hours after administration
Changes in MCNVA(monocular corrected near visual acuity) ETDRS letters from baseline in the study eyes 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).	15 minutes to 8 hours after administration
Changes in BCNVA (Binocular Corrected Near Visual Acuity) ETDRS letters and BCDVA (Binocular Corrected Distance Visual Acuity) ETDRS letters from baseline after administration	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.; 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.; In the mesopic conditions, the proportion of subjects whose BCNVA increased by ≥ 15 ETDRS letters across all post-dose evaluation intervals (15minutes through 8hour).; In the mesopic conditions, the proportion of subjects whose BCNVA increased by ≥ 10 ETDRS letters across all post-dose evaluation intervals (15minutes through 8hour).	15minutes, 1hour, 2hour, 4hour15minutes, 6hour, and 8hour after administration
Changes in pupil diameter from baseline 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.	15minutes, 1hour, 2hour, 4hour15minutes, 6hour, and 8hour after administration

Collaborators and Investigators

• Sponsor: Zhaoke (Guangzhou) Ophthalmology Pharmaceutical Ltd.
• Investigators: Principal Investigator: Jia Qu, Optometry Hospital of Wenzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2025
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: March 6, 2025
• First Submitted That Met QC Criteria: April 23, 2025
• First Posted (Actual): April 29, 2025

Study Record Updates

• Last Update Posted (Actual): April 29, 2025
• Last Update Submitted That Met QC Criteria: April 23, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Chinese; presbyopia; Brimonidine; ophthalmic solution; eye drops; Brimochol; Carbachol
• Additional Relevant MeSH Terms: Eye Diseases; Refractive Errors; Presbyopia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Neurotransmitter Agents; Protective Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Cardiotonic Agents; Pharmaceutical Solutions; Antihypertensive Agents; Cholinergic Agents; Cholinergic Agonists; Miotics; Brimonidine Tartrate; Ophthalmic Solutions; Carbachol
• Other Study ID Numbers: ZKO-CSP-BRI-CAR-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No