Efficacy and Safety of CSF-1 (0.4% Pilocarpine Hydrochloride) in Presbyopia: Pooled Results of the NEAR Phase 3 Randomized, Clinical Trials.

Autor: Holland E; Cincinnati Eye Institute, Edgewood, KY. Electronic address: eholland@holprovision.com., Karpecki P; The Kentucky College of Optometry, University of Pikeville, KY., Fingeret M; Department of Veterans Administration New York Harbor Health Care System, New York, NY., Schaeffer J; Independent Consultant., Gupta P; Triangle Eye Consultants, Raleigh, NC., Fram N; Advanced Vision Care, Los Angeles, CA., Smits G; Orasis Pharmaceuticals, Ponte Vedra, FL., Ignacio T; Orasis Pharmaceuticals, Ponte Vedra, FL., Lindstrom R; Minnesota Eye Consultants, Bloomington, MN.
Jazyk: angličtina
Zdroj: Clinical therapeutics [Clin Ther] 2024 Feb; Vol. 46 (2), pp. 104-113. Date of Electronic Publication: 2024 Jan 11.
DOI: 10.1016/j.clinthera.2023.12.005
Abstrakt: Purpose: This study was undertaken to evaluate the safety and efficacy of CSF-1 (0.4% pilocarpine hydrochloride ophthalmic solution) for use in individuals with presbyopia.
Methods: Two Phase 3 multicenter, randomized, double-masked, vehicle-controlled, parallel-group clinical trials were conducted in 35 private ophthalmology clinics in the United States from October 2020 to February 2022. Key inclusion criteria were the following: (1) age 45-64 years, (2) distance-corrected near visual acuity (DCNVA) at 40 cm ≥0.40 and ≤0.90 logarithm of the minimum angle of resolution (logMAR, approximately 20/50-20/160 Snellen) in at least 1 eye, (3) manifest refraction (MR) between -4.50 and +2.00 diopter (D) sphere in each eye with ≤2.00D difference between eyes, (4) <2.00D of cylinder MR in each eye, (5) ≤0.04 logMAR (20/20-2 or better) corrected distance visual acuity (CDVA) at 4 m in each eye. Key exclusion criteria were the following: (1) >0.14 logMAR (7 letters) improvement in post-vehicle treatment in monocular DCNVA in either eye at visit 1, (2) introcular pressure (IOP) <9 or >22 mm Hg, (3) average dark-adapted pupillometry <3.5 mm in either eye, (4) prior refractive surgery or intraocular lens (IOL) implantation. Participants applied CSF-1 or vehicle twice per day for 2 weeks. Efficacy and safety assessments were performed at several times on days 1, 8, and 15. Response was defined as ≥3-line gain in DCNVA without loss of ≥1-line in CDVA in the study eye under mesopic room lighting conditions. The primary efficacy endpoint was measured 1 hour post-dose 1 on day 8. Key secondary endpoints were 2 hours post-dose 1, and 1 and 2 hours post-dose 2, also on day 8. Safety endpoints were ocular and non-ocular treatment-related adverse events (TRAE), conjunctival redness, drop comfort, slit-lamp biomicroscopy, intraocular pressure, indirect fundoscopy, and CDVA at 4 m.
Findings: Six hundred thirteen participants were randomized to CSF-1 (n = 309) or vehicle (n = 304). Participants were predominantly White (80.8%) and female (62.0%), with mean age (standard deviation) of 54.7 (4.8). CSF-1 met the primary and key secondary endpoints. At the primary endpoint, 40.1% of the CSF-1 group achieved response versus 19.1% of the vehicle group (P < 0.0001). The percentage of responders was significantly greater in CSF-1 compared with vehicle at all tested times. Changes from baseline in all safety endpoints were comparable between groups. Most adverse events (AEs) were mild and transient. Neither serious nor severe AEs were reported with CSF-1.
Implications: CSF-1, a low-dose pilocarpine ophthalmic solution, demonstrated superiority to vehicle in improving near vision in individuals with presbyopia without compromising distance vision. CSF-1 demonstrated a favorable safety profile.
Clinicaltrials: gov identifier: NCT04599933 (NEAR-1), NCT04599972 (NEAR-2).
Competing Interests: Declaration of competing interest Edward Holland is a consultant for Alcon, Aurion Biotech and Orasis. Paul Karpecki is a consultant for Alcon, Aldeyra, Allergan/Abbvie, Apellis, Atlas, Aurion, Avellino, Azura, B+L, BioTissue, Bruder, Bruno, Dompe, Eyedetec, Healthe, Horizon, Imprimis, Iveric, Konan, Mitotech, Neurolens, Novartis, Oasis Medical, Ocuphire, Oculus, OcuMedic, OcuSoft, Olympic Ophthalmics, Orasis, RegenerEyes, Rendia, Reichert, RVL, RxSight, Santen, Science Based Health, Scope, Sentiss, Sight Sciences, Silk Technologies, Sun Pharmaceuticals, Surface, Sydnexis, Tarsus, TearClear, Thea, Vial, Viatris, Visant Medical, Vital Tears, WebMD and is part of the Speaker's Bureau for Bausch + Lomb, Dompe, Mallinckrodt and Sun pharmaceuticals. Murray Fingeret is a consultant for Alcon, Allergan, Bausch + Lomb, Carl Zeiss Meditec, Glaukos, Orasis, Topcon, Tarsus Therapeutics, Visus Therapeutics. Jack Schaeffer has received honorarium, compensation, or serves as an advisor to Alcon, Allergan, AMO/Abbott, Arctic/DX, Bausch & Lomb, Brien Holden Institute, Bruder, Coopervision, Clearpath, Essilor, Hoya, Miboflow, Nicox, Optovue, Optos, Orasis, Sydnexis, Sight Science, Reed, Rodenstock, Tarsus, Tearscience, Topcon, Valeant, Vistakon, WebMD/Jobson, Zeiss Vision. Preeya Gupta is a consultant for Azura, Alcon, Aldeyra, Allergan, Expert Opinion, HanAll Biopharma, J&J Vision, Kala, New World Medical, Novartis, Ocular Science, Ocular Therapeutix, Orasis, Oyster Point, Santen, Sight Sciences, Spyglass, Surface Ophthalmics, Sun Pharmaceuticals, Tarsus, Tear Lab, Tear Clear, Tissue Tech, Inc, Visionology, Zeiss and has stock options for Azura, Expert Opinion, Orasis, Tarsus, Tear Clear, Surface, Spyglass, Visionology, Visant. Nicole Fram is on the Medical Advisory Board of Orasis. Gerard Smits is a consultant for Orasis. Teresa Ignacio is an employee of Orasis. Richard Lindstrom is a consultant for Allergan and J&J Vision, and is a shareholder and part of the medical advisory board of Orasis Pharmaceuticals.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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