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

Dry Eye Syndromes Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00784719
• Other study ID #: A3921034
• Secondary ID: A3921034
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 3, 2008
• Last updated: February 27, 2013
• Start date: November 2008
• Est. completion date: October 2009

Study information

• Verified date: February 2013
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 327
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dry Eye Syndromes
• Keratoconjunctivitis Sicca

Intervention

Drug:
• CP-690,550
Ophthalmic topical solution, low dose, dosed at least once/day, 8 weeks
• CP-690,550
Ophthalmic topical solution, medium dose, dosed at least once/day, 8 weeks
• CP-690,550
Ophthalmic topical solution, intermediate dose, dosed at least once/day, 8 weeks
• CP-690,550
Ophthalmic topical solution, high dose, dosed at least once/day, 8 weeks
• Cyclosporine
Ophthalmic topical solution, 0.05%, dosed at least once/day, 8 weeks
• CP-690,550 Vehicle
Ophthalmic topical solution, dosed at least once/day, 8 weeks

Locations

Country	Name	City	State
United States	Pfizer Investigational Site	Artesia	California
United States	Pfizer Investigational Site	Atlanta	Georgia
United States	Pfizer Investigational Site	Austin	Texas
United States	Pfizer Investigational Site	Austin	Texas
United States	Pfizer Investigational Site	Austin	Texas
United States	Pfizer Investigational Site	Baltimore	Maryland
United States	Pfizer Investigational Site	Boston	Massachusetts
United States	Pfizer Investigational Site	Centennial	Colorado
United States	Pfizer Investigational Site	Chandler	Arizona
United States	Pfizer Investigational Site	Charlotte	North Carolina
United States	Pfizer Investigational Site	Cleveland	Ohio
United States	Pfizer Investigational Site	Columbus	Ohio
United States	Pfizer Investigational Site	High Point	North Carolina
United States	Pfizer Investigational Site	Kansas City	Missouri
United States	Pfizer Investigational Site	Louisville	Kentucky
United States	Pfizer Investigational Site	Lynbrook	New York
United States	Pfizer Investigational Site	Memphis	Tennessee
United States	Pfizer Investigational Site	Morrow	Georgia
United States	Pfizer Investigational Site	Ormond Beach	Florida
United States	Pfizer Investigational Site	Peoria	Arizona
United States	Pfizer Investigational Site	Phoenix	Arizona
United States	Pfizer Investigational Site	Rochester	New York
United States	Pfizer Investigational Site	Roswell	Georgia
United States	Pfizer Investigational Site	San Antonio	Texas
United States	Pfizer Investigational Site	Stuart	Florida
United States	Pfizer Investigational Site	Tamarac	Florida
United States	Pfizer Investigational Site	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

External Links

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