A Prospective, Randomized, Placebo and Active Comparator Controlled Study of CP-690,550 in Subjects With Dry Eye.

Study Overview
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Brief Summary
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A prospective, randomized, placebo and active comparator controlled study of CP-690,550 in subjects with dry eye.

Official Title
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A Phase I/II Prospective, Randomized, Double Masked, Vehicle And Comparator Controlled, Dose Ranging Study Of CP-690,550 In Subjects With Dry Eye Disease.

Conditions
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Dry Eye Syndromes

Intervention / Treatment
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* Drug: CP-690,550
* Drug: CP-690,550
* Drug: CP-690,550
* Drug: CP-690,550
* Drug: Cyclosporine
* Drug: CP-690,550 Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptoms of dry eye for at least 6 months. Signs of moderate to severe dry eye Exclusion Criteria: Women who are nursing or pregnant Participation in other studies within 30 days of screening visit Ocular disorders that may confound interpretation of study results

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment 1<br> | Drug: CP-690,550<br>* Ophthalmic topical solution, low dose, dosed at least once/day, 8 weeks<br>|
| Experimental: Treatment 2<br> | Drug: CP-690,550<br>* Ophthalmic topical solution, medium dose, dosed at least once/day, 8 weeks<br>|
| Experimental: Treatment 3<br> | Drug: CP-690,550<br>* Ophthalmic topical solution, intermediate dose, dosed at least once/day, 8 weeks<br>|
| Experimental: Treatment 4<br> | Drug: CP-690,550<br>* Ophthalmic topical solution, high dose, dosed at least once/day, 8 weeks<br>|
| Active Comparator: Active comparator<br> | Drug: Cyclosporine<br>* Ophthalmic topical solution, 0.05%, dosed at least once/day, 8 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: CP-690,550 Vehicle<br>* Ophthalmic topical solution, dosed at least once/day, 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Systemic Adverse Events (AEs) | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Systemic AEs are the events which are not localized but occur throughout the systemic circulation. | Baseline up to Week 8 | 
| Percentage of Participants With Ocular Adverse Events (AEs) | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Ocular AEs are the events which are localized in the ocular region. | Baseline up to Week 8 | 
| Percentage of Participants With Ocular Tolerability Assessment | Ocular tolerability assessment included evaluation of severity and duration of the 5 symptoms: burning/stinging, blurred vision, ocular discomfort, pain, tearing. Severity was assessed on a 4-point scale, where 0=none, 1=mild, 2=moderate and 3=severe. Duration was assessed as immediate (if subsided within 5 minutes [<5 min] after application) or persistent (if continued beyond 5 minutes [>=5 min] after application). | Baseline up to Week 8 | 
| Percentage of Participants Who Achieved Greater Than or Equal to (>=) 10 Millimeter (mm) Schirmer Wetting Score Without Anesthesia at Week 8 | Schirmer test without anesthesia: well standardized test used to estimate tear flow stimulated reflexly by insertion of a filter paper strip into the conjunctival sac for 5 min. The length of wetting was recorded to the nearest 0.5 millimeter (mm). If the wetting line was oblique, halfway point was used. Results from study eye are reported. Study eye is the 'worse eye', defined as the eye with worse Schirmer test score without anesthesia score at baseline. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Achieve >= 10mm Schirmer Test Score Without Anesthesia | Schirmer test without anesthesia: well standardized test used to estimate tear flow stimulated reflexly by insertion of a filter paper strip into the conjunctival sac for 5 min. The length of wetting was recorded to the nearest 0.5 mm. If the wetting line was oblique, halfway point was used. Results from study eye are reported. Study eye is the 'worse eye', defined as the eye with worse Schirmer test score without anesthesia score at baseline. | Baseline through Week 8 | 
| Time to Achieve 100 Percent (%) Clearance of Corneal Staining | Corneal staining was assessed by instilling sodium fluorescein dye in the eye and after 1 to 2 minutes, observing for corneal staining with the aid of a yellow filter and slit lamp. The cornea was divided into five different zones and each corneal zone was graded independently using a 0 to 3 grading scale; where 0=none, 1=slight, 2=moderate, 3=severe. Results from study eye were to be reported. Study eye is the 'worse eye', defined as the eye with worse Schirmer test score without anesthesia score at baseline. | Baseline through Week 8 | 
| Time to Achieve >= 5 Units Decrease in Ocular Comfort Index (OCI) Score | OCI: validated questionnaire to measure the frequency and intensity of 6 common dry eye symptoms: dryness, grittiness, stinging, eye tiredness, pain, and itching. It contained 12 questions, each measured on a 7-point Likert scale ranging from 0 (never) to 6 (always/severe). Total score was transformed to range of 0 to 100, higher score indicated more ocular discomfort. Negative change from baseline indicated improvement. | Baseline through Week 8 | 
| Change From Baseline in Schirmer Wetting Score Without Anesthesia at Week 1, 2, 4, 6 and 8 | Schirmer test without anesthesia: well standardized test used to estimate tear flow stimulated reflexly by insertion of a filter paper strip into the conjunctival sac for 5 min. The length of wetting was recorded to the nearest 0.5 mm. If the wetting line was oblique, halfway point was used. Results from study eye are reported. Study eye is the 'worse eye', defined as the eye with worse Schirmer test score without anesthesia score at baseline. | Baseline, Week 1, 2, 4, 6, 8 | 
| Change From Baseline in Schirmer Wetting Score With Anesthesia at Week 8 | Schirmer test was performed 2 to 3 minutes after 1 drop of proparacaine 0.5% was placed in lower conjunctival fornix and superior bulbar conjunctiva of each eye. It was used to estimate tear flow stimulated reflexly by insertion of a filter paper strip into the conjunctival sac for 5 min. The length of wetting was recorded to the nearest 0.5 mm. If the wetting line was oblique, halfway point was used. Results from study eye are reported. Study eye is the 'worse eye', defined as the eye with worse Schirmer test score without anesthesia score at baseline. | Baseline, Week 8 | 
| Percentage of Participants Who Achieved >=10 mm Schirmer Wetting Score Without Anesthesia at Week 1, 2, 4 and 6 | Schirmer test without anesthesia: well standardized test used to estimate tear flow stimulated reflexly by insertion of a filter paper strip into the conjunctival sac for 5 min. The length of wetting was recorded to the nearest 0.5 mm. If the wetting line was oblique, halfway point was used. Results from study eye are reported. Study eye is the 'worse eye', defined as the eye with worse Schirmer test score without anesthesia score at baseline. | Week 1, 2, 4, 6 | 
| Percentage of Participants Who Achieved >=10 mm Schirmer Wetting Score With Anesthesia at Week 8 | Schirmer test was performed 2 to 3 minutes after 1 drop of proparacaine 0.5% was placed in lower conjunctival fornix and superior bulbar conjunctiva of each eye. It was used to estimate tear flow stimulated reflexly by insertion of a filter paper strip into the conjunctival sac for 5 min. The length of wetting was recorded to the nearest 0.5 mm. If the wetting line was oblique, halfway point was used. Results from study eye are reported. Study eye is the 'worse eye', defined as the eye with worse Schirmer test score without anesthesia score at baseline. | Week 8 | 
| Change From Baseline in Corneal Staining Scores at Week 1, 2, 4, 6 and 8 | Corneal staining was assessed using fluorescein dye, a yellow filter, and a slit lamp. The cornea was divided into 5 different zones. Each corneal zone was graded independently using a 0 to 3 grading scale; where 0=none, 1=slight, 2=moderate, 3=severe. Sum of scores of each zone led to total score. Total score range: 0 to 15, higher score indicated greater staining. Results from study eye are reported. Study eye is the 'worse eye', defined as the eye with worse Schirmer test score without anesthesia score at baseline. | Baseline, Week 1, 2, 4, 6, 8 | 
| Percentage of Participants Who Demonstrated 100% Clearance of Corneal Staining | Corneal staining was assessed using fluorescein dye, yellow filter, slit lamp. Cornea was divided into 5 different zones. Each corneal zone was graded independently using 0 to 3 grading scale:0=none, 1=slight, 2=moderate, 3=severe. Sum of scores of each zone led to total score. Total score range: 0 to 15, higher score indicated greater staining. Results from study eye are reported. Study eye is the 'worse eye', defined as the eye with worse Schirmer test score without anesthesia score at baseline. | Week 1, 2, 4, 6, 8 | 
| Change From Baseline in Interpalpebral Conjunctival Staining Score at Week 1, 2, 4, 6 and 8 | Interpalpebral conjunctival staining was performed 1 minute following ocular administration of lissamine green dye with aid of slit lamp. Based on Oxford grading system, bulbar conjunctiva was divided into 2 zones: nasal, temporal. Staining were graded using a 6-point scale (0=absent, 5=severe). Total score=sum of 2 zone scores. Total score range: 0 to 10, higher score=higher damage to eyes due to dryness. Negative change from baseline indicated improvement. Results from study eye are reported. Study eye is the eye with worse Schirmer test score without anesthesia score at baseline. | Baseline, Week 1, 2, 4, 6, 8 | 
| Change From Baseline in Tear Break-up Time (TBUT) at Week 1, 2, 4, 6 and 8 | TBUT was the time interval between the last complete blink and the first appearance of a dry spot, or disruption in the tear film. It was measured under a slit lamp following instillation of fluorescein dye in the eye using a stopwatch. Results from study eye are reported. Study eye is the 'worse eye', defined as the eye with worse Schirmer test score without anesthesia score at baseline. | Baseline, Week 1, 2, 4, 6, 8 | 
| Change From Baseline in Ocular Comfort Index (OCI) Score at Week 1, 2, 4, 6 and 8 | OCI: validated questionnaire to measure the frequency and intensity of 6 common dry eye symptoms: dryness, grittiness, stinging, eye tiredness, pain, and itching. It contains 12 questions, each measured on a 7-point Likert scale ranging from 0 (never) to 6 (always/severe). Total score was transformed to range of 0 to 100, higher score indicated more ocular discomfort. Negative change from baseline indicated improvement. | Baseline, Week 1, 2, 4, 6, 8 | 
| Percentage of Participants With >= 5 Units Decrease in Total OCI Score | OCI: validated questionnaire to measure the frequency and intensity of 6 common dry eye symptoms: dryness, grittiness, stinging, eye tiredness, pain, and itching. It contains 12 questions, each measured on a 7-point Likert scale ranging from 0 (never) to 6 (always/severe). Total score was transformed to range of 0 to 100, higher score indicated more ocular discomfort. | Week 1, 2, 4, 6, 8 | 
| Change From Baseline in Daily Artificial Tear Use at Week 1, 2, 4, 6 and 8 | Daily artificial tear use was assessed by collecting data on daily number of drops of artificial tear instilled in the eye using a participant diary. Decrease in daily artificial tear use indicated improvement. | Baseline, Week 1, 2, 4, 6, 8 | 
| Change From Baseline in Ocular Surface Disease Index (OSDI) Total and Subscale Score at Week 1, 2, 4, 6 and 8 | OSDI is a validated instrument for ocular surface disease. It has 12 items, each measured on 5-point Likert scale (0=none of the time, 4=all the time). Based on these item scores, a total OSDI score (question 1 [Q1]-Q12) and three subscale scores can be derived: Ocular Symptom (Q1-Q3), Vision-related function (Q4-Q9), and Environmental trigger (Q10-Q12). Each derived score ranges from 0 to 100, with a higher score indicates worse condition. | Baseline, Week 1, 2, 4, 6, 8 | 
| Percentage of Participants With >= 10 Units Decrease in Total OSDI Score | OSDI is a validated instrument for ocular surface disease. It has 12 items, each has a raw score measured on 5-point Likert scale (0=none of the time, 4=all the time). Based on these item scores, a total OSDI score can be derived which ranges from 0 to 100; a higher score indicates worse ocular disease. | Week 1, 2, 4, 6, 8 | 
| Change From Baseline Ocular Surface Disease Index (OSDI) Raw Score at Week 1, 2, 4, 6 and 8 | OSDI is a validated instrument for ocular surface disease. It has 12 items, each with a raw score measured on 5-point Likert scale (0=none of the time, 4=all the time). | Baseline, Week 1, 2, 4, 6, 8 | 
| Change From Baseline in Modified Ocular Comfort Index (mOCI) Raw Scores at Week 1, 2, 4, 6 and 8 | mOCI consisted of the original 12-item OCI plus additional questions on other dry eye symptoms and their impact to participant's life. Each item was measured on a 7-point Likert scale ranging from 0 (never) to 6 (always/severe). Negative change from baseline indicated improvement. | Baseline, Week 1, 2, 4, 6, 8 | 
| Change From Baseline in National Eye Institute Visual Functioning Questionnaire 25-item Score (NEI-VFQ-25) at Week 8 | NEI-VFQ-25 questionnaire included 25 items based on which overall composite VFQ score and 12 subscales were derived: general health (GH), general vision (GV), ocular pain (OP), near activities (NAct), distance activities (DA), social functioning (SF), mental health (MH), role difficulties (RD), dependency, driving, color vision (CV) and peripheral vision (PV). Response to each question converted to 0-100 score. Each subscale, total score=average of items contributing to score. For each subscale and total score, score range: 0 to 100, higher score=less symptoms/better visual functioning. | Baseline, Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dry eye