PMID- 38216351 OWN - NLM STAT- MEDLINE DCOM- 20240227 LR - 20240416 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 46 IP - 2 DP - 2024 Feb TI - Efficacy and Safety of CSF-1 (0.4% Pilocarpine Hydrochloride) in Presbyopia: Pooled Results of the NEAR Phase 3 Randomized, Clinical Trials. PG - 104-113 LID - S0149-2918(23)00478-2 [pii] LID - 10.1016/j.clinthera.2023.12.005 [doi] AB - 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 0.14 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). CI - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Holland, Edward AU - Holland E AD - Cincinnati Eye Institute, Edgewood, KY. Electronic address: eholland@holprovision.com. FAU - Karpecki, Paul AU - Karpecki P AD - The Kentucky College of Optometry, University of Pikeville, KY. FAU - Fingeret, Murray AU - Fingeret M AD - Department of Veterans Administration New York Harbor Health Care System, New York, NY. FAU - Schaeffer, Jack AU - Schaeffer J AD - Independent Consultant. FAU - Gupta, Preeya AU - Gupta P AD - Triangle Eye Consultants, Raleigh, NC. FAU - Fram, Nicole AU - Fram N AD - Advanced Vision Care, Los Angeles, CA. FAU - Smits, Gerard AU - Smits G AD - Orasis Pharmaceuticals, Ponte Vedra, FL. FAU - Ignacio, Teresa AU - Ignacio T AD - Orasis Pharmaceuticals, Ponte Vedra, FL. FAU - Lindstrom, Richard AU - Lindstrom R AD - Minnesota Eye Consultants, Bloomington, MN. LA - eng SI - ClinicalTrials.gov/NCT04599933 SI - ClinicalTrials.gov/NCT04599972 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20240111 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 81627-83-0 (Macrophage Colony-Stimulating Factor) RN - 0 (Ophthalmic Solutions) RN - 01MI4Q9DI3 (Pilocarpine) SB - IM MH - Female MH - Humans MH - Middle Aged MH - Lens Implantation, Intraocular/adverse effects/methods MH - *Lenses, Intraocular MH - Macrophage Colony-Stimulating Factor MH - Ophthalmic Solutions/adverse effects MH - Pilocarpine/adverse effects MH - *Presbyopia/drug therapy/complications OTO - NOTNLM OT - CSF-1 OT - Low-dose pilocarpine OT - Near vision OT - Presbyopia COIS- 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. EDAT- 2024/01/13 00:42 MHDA- 2024/02/27 06:44 CRDT- 2024/01/12 21:58 PHST- 2023/10/10 00:00 [received] PHST- 2023/12/12 00:00 [revised] PHST- 2023/12/13 00:00 [accepted] PHST- 2024/02/27 06:44 [medline] PHST- 2024/01/13 00:42 [pubmed] PHST- 2024/01/12 21:58 [entrez] AID - S0149-2918(23)00478-2 [pii] AID - 10.1016/j.clinthera.2023.12.005 [doi] PST - ppublish SO - Clin Ther. 2024 Feb;46(2):104-113. doi: 10.1016/j.clinthera.2023.12.005. Epub 2024 Jan 11.