Wirta, David L., Torkildsen, Gail L., Moreira, Helen R., Lonsdale, John D., Ciolino, Joseph B., Jentsch, Garrit, Beckert, Michael, Ousler, George W., Steven, Philipp and Kroesser, Sonja (2019). A Clinical Phase II Study to Assess Efficacy, Safety, and Tolerability of Waterfree Cyclosporine Formulation for Treatment of Dry Eye Disease. Ophthalmology, 126 (6). S. 792 - 801. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1549-4713

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Abstract

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. (C) 2018 by the American Academy of Ophthalmology.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Wirta, David L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Torkildsen, Gail L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moreira, Helen R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lonsdale, John D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ciolino, Joseph B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jentsch, GarritUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beckert, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ousler, George W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steven, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kroesser, SonjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-147404
DOI: 10.1016/j.ophtha.2019.01.024
Journal or Publication Title: Ophthalmology
Volume: 126
Number: 6
Page Range: S. 792 - 801
Date: 2019
Publisher: ELSEVIER SCIENCE INC
Place of Publication: NEW YORK
ISSN: 1549-4713
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
A CATIONIC EMULSION; SYMPTOMS; SIGNS; ASSOCIATION; MULTICENTER; MODERATE; CARRIERMultiple languages
OphthalmologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14740

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