Florent Aptel1, Norbert Pfeiffer2, Stefanie Schmickler3, Jonathan Clarke4, Cosme Lavín-Dapena5, Javier Moreno-Montañés6, Tomasz Żarnowski7, Adrienne Csutak8, Tiia Jugaste9, Lāsma Volksone10, Yury S Astakhov11, Laurent Coupier12, Jean-Philippe Nordmann13, Ingeborg Stalmans14. 1. CHU de Grenoble/University Hospital of Grenoble, Université Grenoble Alpes, Grenoble. 2. Department of Ophthalmology, Mainz University Medical Center, Mainz. 3. Augen-Zentrum-Nordwest, Augenpraxis Ahaus, Ahaus, Germany. 4. NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK. 5. Hospital Universitario La Paz, Madrid. 6. Clínica Universidad de Navarra, Pamplona, Spain. 7. Department of Diagnostics and Microsurgery of Glaucoma, Medical University, Lublin, Poland. 8. Department of Ophthalmology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. 9. Clinic of Ophthalmology, Tallinn, Estonia. 10. Dr Volksone's Practice in Ophthalmology, Lavolks Ltd, Ri[Combining Macron]ga, Latvia. 11. Department of Ophthalmology, Academician I.P. Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia. 12. Centre Hospitalier du Pays d'Aix, Service Ophtalmologie, Aix-en-Provence. 13. Ophthalmology, CHNO des Quinze-Vingts, Paris, France. 14. Department of Ophthalmology, University Hospitals UZ Leuven, Leuven, Belgium.
Abstract
PRéCIS:: Noninferiority of efficacy was demonstrated for a preservative-free latanoprost-timolol fixed combination compared with a BAK-containing formulation at 84 days after treatment in patients with open-angle glaucoma or ocular hypertension. PURPOSE: The purpose of this study was to compare the effect on intraocular pressure and safety of preservative-free latanoprost-timolol fixed combination (T2347) to benzalkonium chloride-preserved latanoprost-timolol fixed combination in patients with open-angle glaucoma or ocular hypertension. METHODS: Phase III, randomized, parallel-group, investigator-masked study in 10 countries. A total of 242 patients aged 18 years or older with open-angle glaucoma or ocular hypertension in both eyes controlled with a preservedlatanoprost-timololfixed combination (15.7±2.4 mm Hg overall before inclusion) were randomized at day 0 with no washout period to receive the preservative-free alternative T2347 (N=127) or remain on the preserved comparator (N=115) for 84 days. Intraocular pressure changes from day 0 were measured at 9:00 am (±1 hour) on day 42 and day 84, and noninferiority of T2347 to the preserved comparator was analyzed statistically at day 84. Safety parameters were also reported. RESULTS: The mean change in intraocular pressure from baseline to day 84 was -0.49±1.80 mm Hg for preservative-free T2347 and -0.49±2.25 mm Hg for the preserved comparator. These results met the noninferiority limits. Similar results were observed at day 42. There was no difference between groups in the incidence of adverse events or ocular signs. The total ocular symptoms score was better for T2347 than BPLT upon instillation at day 84 (45.9%/44.3%/9.8% of patients with improvement/no change/worsening vs. 33.6%/47.3%/19.1%; P=0.021), reflecting improvements in individual symptoms such as irritation/burning/stinging (P<0.001), and itching (P<0.01) on day 84. CONCLUSIONS:Preservative-free latanoprost-timolol fixed combination T2347 showed noninferior efficacy compared with the preserved comparator and was well tolerated.
RCT Entities:
PRéCIS:: Noninferiority of efficacy was demonstrated for a preservative-free latanoprost-timolol fixed combination compared with a BAK-containing formulation at 84 days after treatment in patients with open-angle glaucoma or ocular hypertension. PURPOSE: The purpose of this study was to compare the effect on intraocular pressure and safety of preservative-free latanoprost-timolol fixed combination (T2347) to benzalkonium chloride-preserved latanoprost-timolol fixed combination in patients with open-angle glaucoma or ocular hypertension. METHODS: Phase III, randomized, parallel-group, investigator-masked study in 10 countries. A total of 242 patients aged 18 years or older with open-angle glaucoma or ocular hypertension in both eyes controlled with a preserved latanoprost-timolol fixed combination (15.7±2.4 mm Hg overall before inclusion) were randomized at day 0 with no washout period to receive the preservative-free alternative T2347 (N=127) or remain on the preserved comparator (N=115) for 84 days. Intraocular pressure changes from day 0 were measured at 9:00 am (±1 hour) on day 42 and day 84, and noninferiority of T2347 to the preserved comparator was analyzed statistically at day 84. Safety parameters were also reported. RESULTS: The mean change in intraocular pressure from baseline to day 84 was -0.49±1.80 mm Hg for preservative-free T2347 and -0.49±2.25 mm Hg for the preserved comparator. These results met the noninferiority limits. Similar results were observed at day 42. There was no difference between groups in the incidence of adverse events or ocular signs. The total ocular symptoms score was better for T2347 than BPLT upon instillation at day 84 (45.9%/44.3%/9.8% of patients with improvement/no change/worsening vs. 33.6%/47.3%/19.1%; P=0.021), reflecting improvements in individual symptoms such as irritation/burning/stinging (P<0.001), and itching (P<0.01) on day 84. CONCLUSIONS: Preservative-free latanoprost-timolol fixed combination T2347 showed noninferior efficacy compared with the preserved comparator and was well tolerated.