Elsevier

Ophthalmology

Volume 112, Issue 10, October 2005, Pages 1790-1794
Ophthalmology

Original Article
Phase III Safety Evaluation of Cyclosporine 0.1% Ophthalmic Emulsion Administered Twice Daily to Dry Eye Disease Patients for Up to 3 Years

Paper presented at: American Academy of Ophthalmology Annual Meeting, October, 2004; New Orleans, Louisiana.
https://doi.org/10.1016/j.ophtha.2005.05.013Get rights and content

Objective

To evaluate cyclosporine 0.1% ophthalmic emulsion over a 1- to 3-year period in moderate to severe dry eye disease patients.

Design

Nonrandomized, multicenter, open-label clinical trial extending 2 ophthalmic cyclosporine phase III clinical trials.

Participants

Four hundred twelve patients previously dosed for 6 to 12 months with cyclosporine 0.05% or 0.1% in prior phase III trials.

Intervention

Patients instilled ophthalmic cyclosporine 0.1% twice daily into both eyes for up to 3 consecutive 12-month extension periods.

Main Outcome Measures

Corneal staining, Schirmer tests, and symptom severity assessments were conducted during the first 12-month extension, with a patient survey during the second 12-month extension. Biomicroscopy and visual acuity (VA) examinations, intraocular pressure (IOP) measurements, and adverse effects queries occurred at 6-month intervals.

Results

Mean duration of treatment was 19.8 months. Improvements in objective and subjective measures of dry eye disease were modest, probably because of prior treatment with cyclosporine. Most survey respondents said their symptoms began to resolve in the first 3 months of cyclosporine treatment during the previous phase III clinical trials. At study exit, VA decreased in 12.6% (93/738) and increased in 5.4% (40/738) of eyes by ≥2 lines; severity of biomicroscopy findings increased in 3.4% (chemosis; 26/760), 7.2% (conjunctival hyperemia; 55/760), or 8.5% (tear film debris; 64/756) of eyes; and mean IOP increased 0.18 mmHg relative to baseline. The most common treatment-related adverse events were burning (10.9% of patients [45/412]), stinging (3.9% [16/412]), and conjunctival hyperemia (3.4% [14/412]). No serious treatment-related adverse events occurred. Most patients (95.2% [140/147]) said they would continue cyclosporine therapy; 97.9% (143/146) would recommend it to other dry eye patients.

Conclusions

Therapy of chronic dry eye disease with cyclosporine 0.1% ophthalmic emulsion for 1 to 3 years was safe, well tolerated, and not associated with systemic side effects. The results supplement the safety record of the commercially available cyclosporine 0.05% ophthalmic emulsion.

Section snippets

Materials and Methods

This study was a multicenter open-label extension of two 12-month phase III clinical trials of ophthalmic cyclosporine.11 Institutional review board/ethics committee approval was obtained before the extension study. The previous phase III clinical trials included patients with moderate to severe keratoconjunctivitis sicca who were treated with cyclosporine 0.05% emulsion or cyclosporine 0.1% emulsion for 6 to 12 months.11 (Patients who were treated with cyclosporine for 6 months in the phase

Results

Demographic data are presented in Table 1. The mean age of the 412 participants was 59.4 years, 80.3% were female, and 85.7% were Caucasian.

Of the 412 patients enrolled in the first 12-month extension period, 328 (79.6%) completed it (Table 2). Similarly, 71.9% (138/192) of the patients enrolled in the second extension period completed it, 60.8% (76/125) of the patients enrolled in the third extension period completed it, and 20.8% (26/125) of those enrolled in the third extension period were

Discussion

This trial consisted of 3 consecutive 12-month periods of treatment with cyclosporine 0.1% ophthalmic emulsion instilled twice daily. Treatment during the first 12-month period resulted in modest improvements in objective measures of dry eye disease and no change in subjective measures, which was expected because participants had been treated with cyclosporine emulsion (either 0.05% or 0.1%) for 6 to 12 months before the baseline assessment of this study.11

Adverse event frequencies during this

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Manuscript no. 2004-355.

Research funded by Allergan Inc., Irvine, California.

The authors have no financial interest in the treatment investigated in this study. However, all 4 authors serve on speakers’ bureaus and have received research funding from Allergan Inc., the manufacturer of cyclosporine 0.0 5% ophthalmic solution (Restasis), a product closely related to the treatment used in this study.

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