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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00784719
First received: November 3, 2008
Last updated: February 27, 2013
Last verified: February 2013
  Purpose

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


Condition Intervention Phase
Dry Eye Syndromes
Drug: CP-690,550
Drug: Cyclosporine
Drug: CP-690,550 Vehicle
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Percentage of Participants With Systemic Adverse Events (AEs) [ Time Frame: Baseline up to Week 8 ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants With Ocular Adverse Events (AEs) [ Time Frame: Baseline up to Week 8 ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants With Ocular Tolerability Assessment [ Time Frame: Baseline up to Week 8 ] [ Designated as safety issue: Yes ]
    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).

  • Percentage of Participants Who Achieved Greater Than or Equal to (>=) 10 Millimeter (mm) Schirmer Wetting Score Without Anesthesia at Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Time to Achieve >= 10mm Schirmer Test Score Without Anesthesia [ Time Frame: Baseline through Week 8 ] [ Designated as safety issue: No ]
    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.

  • Time to Achieve 100 Percent (%) Clearance of Corneal Staining [ Time Frame: Baseline through Week 8 ] [ Designated as safety issue: No ]
    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.

  • Time to Achieve >= 5 Units Decrease in Ocular Comfort Index (OCI) Score [ Time Frame: Baseline through Week 8 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Schirmer Wetting Score Without Anesthesia at Week 1, 2, 4, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, 8 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Schirmer Wetting Score With Anesthesia at Week 8 [ Time Frame: Baseline, Week 8 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Achieved >=10 mm Schirmer Wetting Score Without Anesthesia at Week 1, 2, 4 and 6 [ Time Frame: Week 1, 2, 4, 6 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Achieved >=10 mm Schirmer Wetting Score With Anesthesia at Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Corneal Staining Scores at Week 1, 2, 4, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, 8 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Demonstrated 100% Clearance of Corneal Staining [ Time Frame: Week 1, 2, 4, 6, 8 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Interpalpebral Conjunctival Staining Score at Week 1, 2, 4, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, 8 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Tear Break-up Time (TBUT) at Week 1, 2, 4, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, 8 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Ocular Comfort Index (OCI) Score at Week 1, 2, 4, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, 8 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With >= 5 Units Decrease in Total OCI Score [ Time Frame: Week 1, 2, 4, 6, 8 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Daily Artificial Tear Use at Week 1, 2, 4, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, 8 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Ocular Surface Disease Index (OSDI) Total and Subscale Score at Week 1, 2, 4, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, 8 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With >= 10 Units Decrease in Total OSDI Score [ Time Frame: Week 1, 2, 4, 6, 8 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline Ocular Surface Disease Index (OSDI) Raw Score at Week 1, 2, 4, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, 8 ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in Modified Ocular Comfort Index (mOCI) Raw Scores at Week 1, 2, 4, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, 8 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in National Eye Institute Visual Functioning Questionnaire 25-item Score (NEI-VFQ-25) at Week 8 [ Time Frame: Baseline, Week 8 ] [ Designated as safety issue: No ]
    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.


Enrollment: 327
Study Start Date: November 2008
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment 1 Drug: CP-690,550
Ophthalmic topical solution, low dose, dosed at least once/day, 8 weeks
Experimental: Treatment 2 Drug: CP-690,550
Ophthalmic topical solution, medium dose, dosed at least once/day, 8 weeks
Experimental: Treatment 3 Drug: CP-690,550
Ophthalmic topical solution, intermediate dose, dosed at least once/day, 8 weeks
Experimental: Treatment 4 Drug: CP-690,550
Ophthalmic topical solution, high dose, dosed at least once/day, 8 weeks
Active Comparator: Active comparator Drug: Cyclosporine
Ophthalmic topical solution, 0.05%, dosed at least once/day, 8 weeks
Placebo Comparator: Placebo Drug: CP-690,550 Vehicle
Ophthalmic topical solution, dosed at least once/day, 8 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00784719

  Show 27 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00784719     History of Changes
Other Study ID Numbers: A3921034, A3921034
Study First Received: November 3, 2008
Results First Received: November 29, 2012
Last Updated: February 27, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Dry eye

Additional relevant MeSH terms:
Dry Eye Syndromes
Keratoconjunctivitis Sicca
Lacrimal Apparatus Diseases
Eye Diseases
Keratoconjunctivitis
Conjunctivitis
Conjunctival Diseases
Keratitis
Corneal Diseases
Cyclosporins
Cyclosporine
Tofacitinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014