Study of Two Formulations of Cyclosporine Ophthalmic Emulsion in Healthy Volunteers and in Patients With Dry Eye

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability and pharmacokinetics of two formulations of cyclosporine ophthalmic emulsion in healthy adults (parallel-group phase). The parallel-group phase will be followed by a paired-eye phase which will evaluate the safety and tolerability of two formulations of cyclosporine ophthalmic emulsion compared with cyclosporine ophthalmic emulsion (RESTASIS®) in patients with dry eye.

Conditions
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Dry Eye Syndromes

Intervention / Treatment
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* Drug: cyclosporine ophthalmic emulsion Formulation A
* Drug: cyclosporine ophthalmic emulsion Formulation B
* Drug: cyclosporine ophthalmic emulsion Formulation A; cyclosporine ophthalmic emulsion 0.05%
* Drug: cyclosporine ophthalmic emulsion Formulation B; cyclosporine ophthalmic emulsion 0.05%
* Drug: cyclosporine ophthalmic emulsion Formulation A; cyclosporine ophthalmic emulsion Formulation B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parallel-Group Phase: Weigh at least 110 lbs 18 to 45 years old Paired-Eye Phase: Dry eye disease in both eyes Exclusion Criteria: Parallel-Group Phase: Use of nicotine products, any medications, supplements or herbal products or consumption of grapefruit juice within 14 days or anticipated use during the study Has donated blood within 90 days Significant weight change (over 10 lbs) within 60 days Previous use of RESTASIS® Parallel-Group and Paired-Eye Phases: Anticipated wearing of contact lenses during the study or wearing of contact lenses within 14 days Consumption of alcohol products within 72 hours Paired-Eye Phase: Previous ocular surgery Use of RESTASIS® within 30 days

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cyclosporine ophthalmic emulsion Formulation A (Formulation A)<br>Parallel-Group Phase (PGP): cyclosporine ophthalmic emulsion Formulation A | Drug: cyclosporine ophthalmic emulsion Formulation A<br>* One drop of cyclosporine ophthalmic emulsion Formulation A administered to each eye twice daily for 2 days and once in the morning of Day 3.<br>|
| Experimental: cyclosporine ophthalmic emulsion Formulation B (Formulation B)<br>PGP: cyclosporine ophthalmic emulsion Formulation B | Drug: cyclosporine ophthalmic emulsion Formulation B<br>* One drop of cyclosporine ophthalmic emulsion Formulation B administered to each eye twice daily for 2 days and once in the morning of Day 3.<br>|
| Other: Formulation A and cyclosporine ophthalmic emulsion 0.05%<br>Paired-Eye Phase (PEP): cyclosporine ophthalmic emulsion Formulation A and cyclosporine ophthalmic emulsion 0.05% | Drug: cyclosporine ophthalmic emulsion Formulation A; cyclosporine ophthalmic emulsion 0.05%<br>* One drop of cyclosporine ophthalmic emulsion Formulation A administered to one eye and one drop of cyclosporine ophthalmic emulsion 0.05% administered to the opposite eye, twice daily for 1 day.<br>* Other names: RESTASIS®;|
| Other: Formulation B and cyclosporine ophthalmic emulsion 0.05%<br>PEP: cyclosporine ophthalmic emulsion Formulation B and cyclosporine ophthalmic emulsion 0.05% | Drug: cyclosporine ophthalmic emulsion Formulation B; cyclosporine ophthalmic emulsion 0.05%<br>* One drop of cyclosporine ophthalmic emulsion Formulation B administered to one eye and one drop of cyclosporine ophthalmic emulsion 0.05% administered to the opposite eye, twice daily for 1 day.<br>* Other names: RESTASIS®;|
| Experimental: Formulation A and Formulation B<br>PEP: cyclosporine ophthalmic emulsion Formulation A and cyclosporine ophthalmic emulsion Formulation B | Drug: cyclosporine ophthalmic emulsion Formulation A; cyclosporine ophthalmic emulsion Formulation B<br>* One drop of cyclosporine ophthalmic emulsion Formulation A administered to one eye and one drop of cyclosporine ophthalmic emulsion Formulation B administered to the opposite eye, twice daily for 1 day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of Cyclosporine Measured in Blood at Day 1 in the Parallel-Group Phase (PGP) | Concentration of cyclosporine measured in blood at Day 1 of the parallel-group phase (PGP). Blood samples were collected up to 3 hours post-dose and concentrations of cyclosporine were measured. | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Who Reported Ocular Symptoms During the Parallel-Group Phase (PGP) | Number of subjects who reported ocular symptoms of any severity during the parallel-group phase (PGP) of the study. Subjects evaluated the presence and severity of ocular symptoms in each eye. The severity of each symptom (blurring, foreign body sensation, pain, burning/stinging, tearing, and itching) were recorded on a 5-point scale (0=none, +0.5=very mild,+1=mild, +2=moderate, and +3=severe). | 3 Days | 
| Number of Eyes With Ocular Symptoms Post-Dose During the Paired-Eye Phase (PEP) at Day 1 | Number of eyes with ocular symptoms of any severity, post-dose in the paired-eye phase (PEP) at Day 1. Subjects evaluated the presence and severity of ocular symptoms in each eye. The severity of each symptom (blurring, foreign body sensation, pain, burning/stinging, tearing, and itching) were recorded on a 5-point scale (0=none, +0.5=very mild, +1=mild, +2=moderate, and +3=severe). | Day 1 |