Dry Eye Syndromes
Conditions
Brief summary
This study will evaluate a new ophthalmic formulation of cyclosporine (Restasis® X) in patients with moderate to severe dry eye disease in two stages. Up to 3 doses will be studied in Stage 2 based on results from Stage 1. No patients participating in Stage 1 will participate in Stage 2 of this study. This study was terminated and Stage 2 of the study was cancelled.
Interventions
DRUGCyclosporine New Ophthalmic Formulation
Cyclosporine New Ophthalmic Formulation administered as per protocol
DRUGVehicle
Vehicle of cyclosporine administered as per protocol
OTHERSham
Sham administered to non-study eye as per protocol on Day 1
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Moderate to severe dry eye disease in both eyes * Best-corrected visual acuity (BCVA) of 20/100 or better in each eye
Exclusion criteria
* Use of any cyclosporine preparations within 3 months * Use of topical medications, other than artificial tears, in the eyes within 1 month * Use of contact lenses in either eye within 1 month * Stage 2 only: Participation in Stage 1 of this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | First dose of study drug to up to 24 Weeks | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAEs are AEs with an onset that occurs after receiving study drug. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Corneal Staining Score Using a 6-Point Scale | Baseline (Day 1) to Week 12 | Total corneal staining with sodium fluorescein was measured in the study eye using the 6-point Oxford scale \[Grade 0: \<2 dots (best), Grade 1: ≥2 to ≤10 dots, Grade 2: \>10 to ≤32 dots, Grade 3: \>32 to ≤100 dots, Grade 4: \>100 to ≤316 dots and Grade 5: \>316 dots or ulcer/erosion (worst)\]. The study eye was defined as the eye that received the dosing level of the treatment received. A negative change from Baseline represents a decrease in staining (improvement). Corneal Staining Score was originally registered as a Primary endpoint but it is actually an exploratory endpoint. |
Countries
United States
Participant flow
Pre-assignment details
This study was terminated. Stage 2 of the study was not conducted.
Participants by arm
| Arm | Count |
|---|---|
| Stage 1 Cohort 5A Cyclosporine New Ophthalmic Formulation Dose D administered to the study eye and vehicle administered to the non-study eye on Day 1. | 8 |
| Stage 1 Cohort 4 Cyclosporine New Ophthalmic Formulation Dose C administered to study eye and Vehicle administered to non-study eye on Day 1. | 8 |
| Stage 1 Cohort 6C Cyclosporine New Ophthalmic Formulation Dose C administered to study eye and Vehicle administered to non-study eye on Day 1 and retreatment at Week 12 if applicable. | 4 |
| Stage 1 Cohort 3 Cyclosporine New Ophthalmic Formulation Dose B administered to study eye and Vehicle administered to non-study eye on Day 1. | 8 |
| Stage 1 Cohort 2 Cyclosporine New Ophthalmic Formulation Dose A administered to study eye and Vehicle administered to non-study eye on Day 1. | 4 |
| Stage 1 Cohort 6B Cyclosporine New Ophthalmic Formulation Dose F administered to study eye and Vehicle administered to non-study eye on Day 1. | 8 |
| Stage 1 Cohort 6D Cyclosporine New Ophthalmic Formulation Dose F administered to study eye and Vehicle administered to non-study eye on Day 1 and retreatment at Week 12 if applicable. | 4 |
| Stage 1 Cohort 6A Cyclosporine New Ophthalmic Formulation Dose E administered to study eye and Vehicle administered to non-study eye on Day 1. | 8 |
| Stage 1 Cohort 1 Vehicle administered to study eye and Sham administered to non-study eye on Day 1. | 3 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 0 |
| Period 1 | Other Miscellaneous Reasons | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Stage 1 Cohort 5A | Stage 1 Cohort 4 | Stage 1 Cohort 6C | Stage 1 Cohort 3 | Stage 1 Cohort 2 | Stage 1 Cohort 6B | Stage 1 Cohort 6D | Stage 1 Cohort 6A | Stage 1 Cohort 1 | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 52.8 years STANDARD_DEVIATION 14.47 | 55.3 years STANDARD_DEVIATION 6.58 | 58.5 years STANDARD_DEVIATION 6.95 | 50.1 years STANDARD_DEVIATION 15.06 | 52.3 years STANDARD_DEVIATION 11.64 | 57.4 years STANDARD_DEVIATION 10.69 | 52.8 years STANDARD_DEVIATION 13.45 | 53.1 years STANDARD_DEVIATION 12.19 | 56.0 years STANDARD_DEVIATION 7.55 | 54.0 years STANDARD_DEVIATION 11.19 |
| Age, Customized 45 to 65 years | 5 Participants | 7 Participants | 3 Participants | 5 Participants | 2 Participants | 5 Participants | 1 Participants | 5 Participants | 3 Participants | 36 Participants |
| Age, Customized <45 years | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 10 Participants |
| Age, Customized >65 years | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 9 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 8 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Hispanic | 7 Participants | 6 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 7 Participants | 2 Participants | 33 Participants |
| Race/Ethnicity, Customized White | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 10 Participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 3 Participants | 5 Participants | 3 Participants | 6 Participants | 1 Participants | 7 Participants | 2 Participants | 40 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants | 3 Participants | 1 Participants | 1 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 4 | 0 / 8 | 0 / 4 | 0 / 8 | 0 / 4 | 0 / 8 | 0 / 3 |
| other Total, other adverse events | 7 / 8 | 8 / 8 | 4 / 4 | 6 / 8 | 4 / 4 | 7 / 8 | 3 / 4 | 5 / 8 | 3 / 3 |
| serious Total, serious adverse events | 0 / 8 | 1 / 8 | 0 / 4 | 0 / 8 | 0 / 4 | 0 / 8 | 0 / 4 | 0 / 8 | 0 / 3 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAEs are AEs with an onset that occurs after receiving study drug.
Time frame: First dose of study drug to up to 24 Weeks
Population: Safety Population included all participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stage 1 Cohort 5A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 7 Participants |
| Stage 1 Cohort 4 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 8 Participants |
| Stage 1 Cohort 6C | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 4 Participants |
| Stage 1 Cohort 3 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 6 Participants |
| Stage 1 Cohort 2 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 4 Participants |
| Stage 1 Cohort 6B | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 7 Participants |
| Stage 1 Cohort 6D | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 3 Participants |
| Stage 1 Cohort 6A | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 5 Participants |
| Stage 1 Cohort 1 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 3 Participants |
Other Pre-specified
Change From Baseline in Corneal Staining Score Using a 6-Point Scale
Total corneal staining with sodium fluorescein was measured in the study eye using the 6-point Oxford scale \[Grade 0: \<2 dots (best), Grade 1: ≥2 to ≤10 dots, Grade 2: \>10 to ≤32 dots, Grade 3: \>32 to ≤100 dots, Grade 4: \>100 to ≤316 dots and Grade 5: \>316 dots or ulcer/erosion (worst)\]. The study eye was defined as the eye that received the dosing level of the treatment received. A negative change from Baseline represents a decrease in staining (improvement). Corneal Staining Score was originally registered as a Primary endpoint but it is actually an exploratory endpoint.
Time frame: Baseline (Day 1) to Week 12
Population: Modified Intent-to-treat (mITT) Population included all participant who received study treatment and had Baseline and at least 1 post-baseline assessment. Analyses includes participants who had data at both Baseline and Week 12.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1 Cohort 5A | Change From Baseline in Corneal Staining Score Using a 6-Point Scale | Baseline | 2.5 score on a scale | Standard Deviation 0.55 |
| Stage 1 Cohort 5A | Change From Baseline in Corneal Staining Score Using a 6-Point Scale | Change from Baseline to Week 12 | -0.8 score on a scale | Standard Deviation 1.33 |