A Clinical Phase II Study to Assess Efficacy, Safety, and Tolerability of Waterfree Cyclosporine Formulation for Treatment of Dry Eye Disease
| Autor: | Helen R. Moreira, Sonja Krösser, Garrit Jentsch, Philipp Steven, David Wirta, Joseph B. Ciolino, John D. Lonsdale, Michael Beckert, George W Ousler, Gail Torkildsen |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
medicine.medical_specialty Visual Analog Scale Visual analogue scale Drug Compounding Phases of clinical research Administration Ophthalmic Article law.invention Cornea 03 medical and health sciences 0302 clinical medicine Randomized controlled trial Double-Blind Method law Ophthalmology Sickness Impact Profile medicine Humans Ocular Surface Disease Index 030304 developmental biology Aged Fluorescent Dyes 0303 health sciences business.industry Middle Aged Clinical trial medicine.anatomical_structure Treatment Outcome Tolerability Tears 030221 ophthalmology & optometry Cyclosporine Quality of Life Dry Eye Syndromes Female Fluorescein Onset of action Ophthalmic Solutions business Immunosuppressive Agents |
| Zdroj: | Ophthalmology |
| ISSN: | 1549-4713 0161-6420 |
| Popis: | Purpose: To compare the efficacy, safety, and tolerability of waterfree cyclosporine formulation (CyclASol) at 2 concentrations (0.1% and 0.05% of cyclosporine [CsA]) to vehicle when applied twice daily for 16 weeks in patients with dry eye disease (DED). An open-label Restasis (Allergan, Irvine, CA) arm was included to allow a direct comparison with an approved therapy. Design: An exploratory phase II, multicenter, randomized, vehicle-controlled clinical trial, double-masked between CyclASol and vehicle with an open-label comparator. Participants: Two hundred and seven eligible patients with a history of dry eye disease were randomized 1:1:1:1 to 1 of 4 treatment arms (CyclASol 0.05%, n = 51; CyclASol 0.1%, n = 51; vehicle, n = 52, and Restasis, n = 53). Methods: After a 2-week run-in period with twice-daily dosing of Systane Balance (Alcon, Fort Worth, TX), patients were randomized to the respective treatment arm and dosed twice daily for 16 weeks. Main Outcome Measures: The study was set up to explore efficacy on a number of sign and symptom end points including total and subregion corneal fluorescein staining, conjunctival staining, visual analog scale (VAS) for dry eye symptoms VAS severity, and Ocular Surface Disease Index (OSDI) questionnaire. Results: CyclASol showed a consistent reduction in corneal and conjunctival staining compared with both vehicle and Restasis over the 16-week treatment period, with an early onset of effect (at day 14). A mixed-effects model–based approach demonstrated that the CyclASol drug effect was statistically significant over vehicle (total corneal staining P < 0.1, central corneal staining P < 0.001, conjunctival staining P < 0.01). This model-based analysis suggests a significant CyclASol effect for OSDI as symptom parameter (P < 0.01). The numbers of ocular adverse events were low in all treatment groups. Conclusions: CyclASol showed efficacy, safety, and tolerability at 2 concentrations in moderate-to-severe DED. In a direct head-to-head against open-label Restasis, CyclASol was found to have an earlier onset of action, as early as after 2 weeks of treatment, in relieving the signs of DED, as measured by corneal and conjunctival staining. The central region of the cornea, an important area for visual function in dry eye sufferers, was shown to have the most benefit from treatment. Excellent safety, tolerability, and comfort profile supports this new CsA formulation as having a positive benefit-to-risk ratio. |
| Databáze: | OpenAIRE |
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