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Clinical Trial
. 2023 Sep 1:17:2575-2588.
doi: 10.2147/OPTH.S414015. eCollection 2023.

Preservative-Free versus Benzalkonium Chloride-Preserved Latanoprost Ophthalmic Solution in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: A Phase 3 US Clinical Trial

Jason Bacharach  1 , Iqbal Ike K Ahmed  2 , Elizabeth D Sharpe  3 , Michael S Korenfeld  4 , Steven Zhang  5 , Christophe Baudouin  6
Affiliations
Clinical Trial

Preservative-Free versus Benzalkonium Chloride-Preserved Latanoprost Ophthalmic Solution in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: A Phase 3 US Clinical Trial

Jason Bacharach et al. Clin Ophthalmol. .

Erratum in

Abstract

Purpose: To evaluate the safety and efficacy of a preservative-free latanoprost 0.005% formulation (T2345) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT) compared to benzalkonium chloride-preserved latanoprost 0.005% (BPL) formulation in the United States (US).

Patients and methods: A prospective, randomized, multicenter, observer-masked, parallel-group study enrolled 335 patients diagnosed with POAG or OHT from 31 US sites who had adequately controlled intraocular pressure (IOP; ≤18 mm Hg) with latanoprost monotherapy. After a ≥72-hour washout period, patients were randomized to T2345 (n=165) or BPL (n=170) groups. Study drugs were dosed once-daily from Day 0 to Day 84 in one or both eyes. The study eye was the eye with lower IOP at baseline. The primary efficacy measure was the between-group comparison of the mean IOP values in the study eye at each time point (8 AM, 10 AM, and 4 PM on Days 15, 42, and 84). Safety measurements included ocular and systemic treatment-emergent adverse events (TEAEs).

Results: Both T2345 and BPL adequately controlled IOP with 95% CIs within 1.5 mm Hg in the study eye at all assessed time points. The percentages of patients with diurnal IOP <18 mm Hg at Day 84 were 73.1% vs 78.7% for the T2345 and BPL groups, respectively. Adverse events were generally mild-to-moderate and primarily ocular. Fewer patients in the T2345 group experienced ocular TEAEs (13.9% vs 22.5%, respectively) and TEAEs with a suspected relationship to the study medication compared with the BPL group (5.5% vs 11.8%, respectively). The most common ocular TEAEs were instillation site pain and conjunctival hyperemia.

Conclusion: In patients with POAG or OHT, both T2345 and BPL maintained IOP at or below clinically meaningful values for the duration of the study. T2345 showed a favorable safety profile, with numerically lower incidences of ocular TEAEs than BPL.

Keywords: benzalkonium chloride; glaucoma; intraocular pressure; latanoprost; ocular hypertension; preservative.

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Conflict of interest statement

Dr. Michael S. Korenfeld is a consultant for Novartis, Orasis, EyePoint Pharmaceuticals, Allysta Pharmaceuticals, Jotteq, Santen, and ZEISS. Prof. Christophe Baudouin is a consultant for AbbVie, Alcon, Horus Pharma, Oculis, Santen, and Théa. Dr. Steven Zhang is employed by Thea Pharma. Inc. Dr. Bacharach is a consultant for Thea Pharma Inc. and receives funding for research from Thea Pharma Inc. Dr. Ike K. Ahmed reports C-Consultant/Consulting Fees S-Speakers Honoraria/ R- Research Grant/Support from: 1. Aequus: C 2. Ace Vision: C 3. Aerie Pharmaceuticals: C, R 4. Akorn: C 5. Alcon: C,S,R 6. Allergan: C,S,R 7. Aquea Health, Inc: C 8. ArcScan: C 9. Avellino Lab USA, Inc: C 10. Avisi: C 11. Bausch Health: C 12. Beaver Visitec: C 13. Beyeonics: C 14. Bionode: C, R 15. Carl Zeiss Meditec: C,S 16. Centricity Vision, Inc: C 17. CorNeat Vision: C 18. Custom Surgical: C 19. Elios Vision: C 20. ElutiMed: C 21. Equinox: C 22. eyeFlow, Inc: C 23. EyeMed: C 24. EyeQ Technologies: C 25. Exhaura Limited: C 26. Genentech: C 27. Glaukos: C, R 28. Gore: C 29. Heine: C, S 30. Heru: C 31. Iantrek: C 32. InjectSense: C 33. Iridex: C 34. iCare: R 35. iStar: C 36. Ivantis: C, R 37. Johnson & Johnson Vision: C, S, R 38. Labtician Thea: C 39. LayerBio: C 40. Leica Microsystems: C 41. Life Long Vision: C 42. Long Bridge Medical, Inc: C 43. MicroOptx: C 44. MST Surgical: C, S 45. Myra Vision: C 46. New World Medical: C, R 47. NovaEye: C 48. Ocular Instruments: C 49. Ocular Therapeutix: C 50. Oculo: C 51. Oculus Surgical: C 52. Omega Ophthalmics: C 53. PolyActiva: C 54. PulseMedica: C 55. Radiance Therapeutics, Inc: C 56. Radius XR: C 57. Rheon Medical SA: C 58. Ripple Therapeutics: C 59. Sanoculis: C 60. Santen: C, R 61. Singapore Biodesign Programme Office 62. Shifamed, LLC: C 63. Sight Sciences: C 64. Smartlens, Inc: C 65. Stroma: C 66. Thea Pharma: C 67. TFS Health Science: C 68. ViaLase: C 69. Visus Therapeutics: C 70. Vizzario: C 71. VSY Biotechnology: C 72. Zilia, Inc: C. Dr. Elizabeth Sharpe works solely for the Veterans Administration. She is not a paid consultant for or an employee of any other company. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Patient disposition (a), and study design (b), specifying the timings of screening, washout periods, and assessment schedule timings. *One patient was initially assigned a specific randomization number, but the study medication for this number (BPL) was unusable because it had frozen on the delivery dock. In accordance with the protocol, the patient was assigned the next randomization number, which specified T2345 administration. This patient was analyzed with the T2345 group for the safety population (actual treatment) and with the BPL group for the ITT population. The patient was excluded from the PP population. **Patient had ≥1 discontinuing reason. AE, adverse event; BAK, benzalkonium chloride; BPL, BAK-preserved latanoprost 0.005%; ITT, intent-to-treat; LTFU, lost to follow-up; PP, per protocol; T2345, preservative-free single-dose latanoprost 0.005%.
Figure 2
Figure 2
Mean IOP values in the study eye in the T2345 and BPL-treated groups (a) and difference in IOP (mm Hg) change from baseline levels between each group at each time point (intent-to-treat population; (b), and in the contralateral eye (c and d).
Figure 3
Figure 3
Proportion of patients with IOP <18 mm Hg in the study eye (per-protocol population).
Figure 4
Figure 4
Investigator assessment of comfort of the study medication scores (safety population) split by treatment group and assessment date.
See this image and copyright information in PMC

References

    1. Tham Y-C, Li X, Wong TY, Quigley HA, Aung T, Cheng C-Y. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014;121(11):2081–2090. doi:10.1016/j.ophtha.2014.05.013 - DOI - PubMed
    1. Allison K, Patel D, Alabi O. Epidemiology of glaucoma: the past, present, and predictions for the future. Cureus. 2020;12(11):e11686. doi:10.7759/cureus.11686 - DOI - PMC - PubMed
    1. Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA. 2014;311(18):1901–1911. doi:10.1001/jama.2014.3192 - DOI - PMC - PubMed
    1. Musch DC, Gillespie BW, Lichter PR, Niziol LM, Janz NK, CIGTS Study Investigators. Visual field progression in the Collaborative Initial Glaucoma Treatment Study: The impact of treatment and other baseline factors. Ophthalmology. 2009;116(2):200–207. doi:10.1016/j.ophtha.2008.08.051 - DOI - PMC - PubMed
    1. Nouri-Mahdavi K, Hoffman D, Coleman AL, et al. Predictive factors for glaucomatous visual field progression in the Advanced Glaucoma Intervention Study. Ophthalmology. 2004;111(9):1627–1635. doi:10.1016/j.ophtha.2004.02.017 - DOI - PubMed