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.

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.
Competing Interests: 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.
(© 2023 Bacharach et al.)