A Phase II, Dose Ranging Study Of CP-690,550 Eye Drops In Patients With Dry Eye Disease

Study Overview
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Brief Summary
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The purpose of the study is to evaluate dose-response, efficacy and safety of CP-690,550 eye drops in patients with dry eye disease.

Official Title
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A Phase II, Prospective, Randomized, Double Masked/Investigator Masked, Vehicle And Comparator (Sodium Hyaluronate Eye Drops) Controlled, Dose Ranging Study Of CP-690,550 Eye Drops In Subjects With Dry Eye Disease

Conditions
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Dry Eye Syndromes

Intervention / Treatment
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* Drug: CP-690,550 Eye drops
* Drug: CP-690,550 Eye drops
* Drug: CP-690,550 Eye drops
* Drug: CP-690,550 Eye drops-vehicle
* Drug: Sodium Hyaluronate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjective symptoms of dry eye for at least 6 months Signs of moderate to severe dry eye (corneal staining score and schirmer test without anesthesia) Exclusion Criteria: Women who are nursing, pregnant or planning pregnancy during the study 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: 20 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 Eye drops<br>* Ophthalmic topical solution, low dose, dosed once/day, 8 weeks<br>|
| Experimental: Treatment 2<br> | Drug: CP-690,550 Eye drops<br>* Ophthalmic topical solution, medium dose, dosed once/day, 8 weeks<br>|
| Experimental: Treatment 3<br> | Drug: CP-690,550 Eye drops<br>* Ophthalmic topical solution, high dose, dosed once/day, 8 weeks<br>|
| Placebo Comparator: Treatment 4<br> | Drug: CP-690,550 Eye drops-vehicle<br>* Ophthalmic topical solution, vehicle, dosed once/day, 8 weeks<br>|
| Active Comparator: Treatment 5<br> | Drug: Sodium Hyaluronate<br>* Ophthalmic topical solution, dosed 6 times/day, 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Corneal Staining Scores for Study Eye From Baseline at Week 8 | Based on the National Eye Institute (NEI) dry eye clinical trials workshop, the cornea was divided into 5 different zones. Each corneal zone was graded independently using a 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. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. Change: score at observation minus score at baseline. Negative change from baseline indicated improvement. | Baseline, Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Corneal Staining Scores for Study Eye From Baseline | Based on the National Eye Institute (NEI) dry eye clinical trials workshop, the cornea was divided into 5 different zones. Each corneal zone was graded independently using a 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. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. Change: score at observation minus score at baseline. Negative change from baseline indicated improvement. | Baseline, Week 1, 2 and 4 | 
| Percentage of Participants Demonstrating 100 Percent Clearing of Corneal Staining for Study Eye | Percentage of participants demonstrating corneal staining score = 0 which indicates no damage in corneal surface. Results from study eye are reported. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. | Week 1, 2, 4 and 8 | 
| Changes in Conjunctival Staining Scores (Interpalpebral) for Study Eye From Baseline | Based on the Oxford grading system, the bulbar conjunctiva of each eye was divided into 2 different zones (nasal and temporal). The nasal and temporal bulbar conjunctival zones were each graded independently using a 6-point scale (0 [Absent] to 5 [Severe]). Total score ranged from 0 (Absent) to 10 (severe), higher score=higher damage to eyes due to dryness. Results from study eye are reported. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. Change = scores at observation minus score at baseline. Negative change from baseline indicated improvement. | Baseline, Week 1, 2, 4 and 8 | 
| Changes in Tear Break Up Time (TBUT) for Study Eye From Baseline | TBUT is the interval between the last complete blink and the first appearance of a dry spot, or disruption in the tear film. Using a stopwatch, the time between last complete blink and first appearance of dry spot was recorded. Results from study eye are reported. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. Change: value at observation minus value at baseline. Positive change from baseline indicated improvement. | Baseline, Week 1, 2, 4 and 8 | 
| Changes in Schirmer Test Values Without Anesthesia for Study Eye From Baseline | The Schirmer test without anesthesia was used to estimate tear flow stimulated reflexly by insertion of a filter paper strip into the conjunctival sac. The length of wetting (distance from the notch) was recorded in millimeters (to the nearest 0.5 mm). If the wetting line was oblique, the halfway point was used. Results from study eye are reported. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. Change: value at observation minus value at baseline. Positive change from baseline indicated improvement. | Baseline, Week 1, 2, 4 and 8 | 
| Percentage of Participants Who Achieve ≥10 mm Schirmer Test Value Without Anesthesia for Study Eye | The Schirmer test without anesthesia was used to estimate tear flow stimulated reflexly by insertion of a filter paper strip into the conjunctival sac. The length of wetting (distance from the notch) was recorded in millimeters (to the nearest 0.5 mm). If the wetting line was oblique, the halfway point was used. Results from study eye are reported. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. | Week 1, 2, 4 and 8 | 
| Number of Participants Who Increase of ≥10 mm From Baseline in Schirmer Test Value Without Anesthesia for Study Eye | The Schirmer test without anesthesia was used to estimate tear flow stimulated reflexly by insertion of a filter paper strip into the conjunctival sac. The length of wetting (distance from the notch) was recorded in millimeters (to the nearest 0.5 mm). If the wetting line was oblique, the halfway point was used. Results from study eye are reported. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. | Week 1, 2, 4 and 8 | 
| Changes in the Ocular Comfort Index (OCI) Total Score From Baseline | The OCI is a validated instrument developed 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 rating scale (0 [Never] to 6 [Always], or 0 [Never had it] to 6 [Severe]). Total score ranged from 0 (none) to 72 (severe symptoms). A higher score indicates more severe dry eye symptoms. Results from study eye are reported. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. Change: score at observation minus score at baseline. Negative change from baseline indicated improvement. | Baseline, Week 1, 2, 4 and 8 | 
| Number of Participants Demonstrating at Least ≥3 Unit Decrease in Ocular Comfort Index (OCI) Total Score From Baseline | The OCI is a validated instrument developed 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 rating scale (0 [Never] to 6 [Always], or 0 [Never had it] to 6 [Severe]). Total score ranged from 0 (none) to 72 (severe symptoms). A higher score indicates more severe dry eye symptoms. Results from study eye are reported. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. Change = scores at observation minus score at baseline. Negative change from baseline indicated improvement. | Week 1, 2, 4 and 8 | 
| Changes in the Ocular Surface Disease Index (OSDI) Total Score From Baseline | The OSDI is a validated instrument for ocular surface diseases, measuring the ocular symptoms, vision-related function, and environmental triggers. The 12 items of the OSDI questionnaire were graded on a scale of 0 [none of the time] to 4 [all of the time]. The total OSDI score was then calculated on the basis of the following formula: OSDI=[(sum of scores for all questions answered) × 100]/[(total number of questions answered) × 4]. The OSDI is scored on a scale of 0 to 100, with higher scores representing greater disability. Results from study eye are reported. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. Change: score at observation minus score at baseline. Negative change from baseline indicated improvement. | Baseline, Week 1, 2, 4 and 8 | 
| Changes in the Ocular Surface Disease Index (OSDI) Subscale Score From Baseline: Ocular Symptoms | The OSDI is a validated instrument for ocular surface diseases, measuring the ocular symptoms, vision-related function, and environmental triggers. The 12 items of the OSDI questionnaire were graded on a scale of 0 [the none of time] to 4 [all of the time]. The subscale OSDI score was then calculated on the basis of the following formula: OSDI=[(sum of scores for questions 1 to 3 answered) × 100]/[(total number of questions 1 to 3 answered) × 4]. The OSDI is scored on a scale of 0 to 100, with higher scores representing greater disability. Results from study eye are reported. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. Change: score at observation minus score at baseline. Negative change from baseline indicated improvement. | Baseline, Week 1, 2, 4 and 8 | 
| Changes in the Ocular Surface Disease Index (OSDI) Subscale Score From Baseline: Vision-Related Function | The OSDI is a validated instrument for ocular surface diseases, measuring the ocular symptoms, vision-related function, and environmental triggers. The 12 items of the OSDI questionnaire were graded on a scale of 0 [none of the time] to 4 [all of the time]. The subscale OSDI score was then calculated on the basis of the following formula: OSDI=[(sum of scores for questions 4 to 9 answered) × 100]/[(total number of questions 4 to 9 answered) × 4]. Thus, the OSDI is scored on a scale of 0 to 100, with higher scores representing greater disability. Results from study eye are reported. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. Change: score at observation minus score at baseline. Negative change from baseline indicated improvement. | Baseline, Week 1, 2, 4 and 8 | 
| Changes in the Ocular Surface Disease Index (OSDI) Subscale Score From Baseline: Environmental Triggers | The OSDI is a validated instrument for ocular surface diseases, measuring the ocular symptoms, vision-related function, and environmental triggers. The 12 items of the OSDI questionnaire were graded on a scale of 0 [none of the time] to 4 [all of the time]. The subscale OSDI score was then calculated on the basis of the following formula: OSDI=[(sum of scores for questions 10 to 12 answered) × 100]/[(total number of questions 10 to 12 answered) × 4]. The OSDI is scored on a scale of 0 to 100, with higher scores representing greater disability. Results from study eye are reported. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. Change: score at observation minus score at baseline. Negative change from baseline indicated improvement. | Baseline, Week 1, 2, 4 and 8 | 
| Percentage of Participants Demonstrating ≥10 Unit Decrease in Ocular Surface Disease Index (OSDI) Total Score From Baseline | The OSDI is a validated instrument for ocular surface diseases, measuring the ocular symptoms, vision-related function, and environmental triggers. The 12 items of the OSDI questionnaire were graded on a scale of 0 [none of the time] to 4 [all of the time]. The total OSDI score was then calculated on the basis of the following formula: OSDI=[(sum of scores for all questions answered) × 100]/[(total number of questions answered) × 4]. The OSDI is scored on a scale of 0 to 100, with higher scores representing greater disability. Results from study eye are reported. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. | Week 1, 2, 4 and 8 | 
| Number of Participants Evaluable for Time to Achievement of 100% Clearing of Corneal Staining for Study Eye | Based on the National Eye Institute (NEI) dry eye clinical trials workshop, the cornea was divided into 5 different zones. Each corneal zone was graded independently using a 0 to 3 grading scale. The maximum possible staining score is 15, higher score indicated greater staining. 100% Clearing of Corneal Staining means corneal staining score = 0. Results from study eye are reported. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. | Week 8 | 
| Number of Participants Evaluable for Time to Achievement of ≥10 mm Schirmer Wetting Score Without Anesthesia for Study Eye | The Schirmer test without anesthesia was used to estimate tear flow stimulated reflexly by insertion of a filter paper strip into the conjunctival sac. Results from study eye are reported. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. | Week 8 | 
| Number of Participants Evaluable for Time to Achievement of ≥3 Unit Decrease in OCI Scores | The OCI is a validated instrument developed 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 rating scale (0 [Never] to 6 [Always], or 0 [Never had it] to 6 [Severe]). Negative change from baseline indicated improvement. Results from study eye are reported. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. | Week 8 | 
| Number of Participants With Ocular Adverse Events (AEs)by Severity | Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Ocular AEs are the events which are localized in the ocular region. Participants with multiple occurrences of an AE within a category were counted once within the category. | 8 weeks | 
| Number of Participants With Nonocular Adverse Events (AEs) by Severity | Counts of participants who had treatment-emergent nonocular AEs, defined as newly occurring or worsening after first dose. Participants with multiple occurrences of an AE within a category were counted once within the category. | 8 weeks | 
| Summary of Maximum Severity of Ocular Tolerability Assessments Post Baseline for Study Eye: Number of Participants in Each Severity Scale | Ocular tolerability was assessed for the 5 symptoms (burning sensation, blurred vision, ocular discomfort, pain, tearing), based on a 4-point severity scale (none, minor, moderate, and severe). Results from study eye are reported. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. | 8 weeks | 

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