Dry Eye Syndromes
Conditions
Keywords
OPC-12759, Dry eye syndromes
Brief summary
The purpose of this study is to evaluate the dose-response of OPC-12759 ophthalmic suspension in dry eye patients.
Interventions
DRUG0.5% OPC-12759
DRUG1% OPC-12759
DRUG2% OPC-12759
DRUGplacebo
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Outpatient. 2. Subjective complaint of dry eye that has been present for minimum 20 months. 3. Primary ocular discomfort severity is moderate to severe. 4. Corneal - conjunctival damage is moderate to severe. 5. Unanesthetized Schirmer's test score of 7mm/5minutes or less. 6. Best corrected visual acuity of 0.2 or better in both eyes.
Exclusion criteria
1. Presence of anterior segment disease or disorder other than that associated with keratoconjunctivitis sicca. 2. Anticipated use of any topically-instilled ocular medications or patients with cannot discontinue the use during the study. 3. Anticipated use of contact lens during the study. 4. Any history of ocular surgery within 12 months. 5. Female patients who are pregnant, possibly pregnant or breast feeding; 6. Known hypersensitivity to any component of the study drug or procedural medications. 7. Receipt of any investigational product within 4 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fluorescein Corneal Staining (FCS) Score From Baseline to Last Observation Carried Forward (LOCF) | baseline, 12 weeks | FCS indicates the damage to the corneal epithelium. Per the National Eye Institute/Industry Workshop report, the cornea was divided into 5 fractions, each of which was given a staining score from 0 to 3, and the total score was calculated (0-15). 0 is better. The change from baseline (CFB) to LOCF at the end of instillation (LOCF endpoint) was used to analyze dose-response. A general linear model was used to examine if slope parameters were not equal to zero. |
| Change in Primary Ocular Discomfort (POD) Score From Baseline to Last Observation Carried Forward (LOCF) | Baseline, 12 weeks | POD indicates the ocular symptom most bothersome to the patient. POD selected by each patient from among the following ocular symptoms; Foreign body sensation, Dryness, Photophobia, Eye pain and Blurred vision. POD was scored from 0 through 4; a score of 0 indicated no symptoms and a score of 4 indicated very severe symptoms. 0 is better. The change from baseline (CFB) to LOCF at the end of instillation (LOCF endpoint) was used to analyze dose-response. A general linear model was used to examine if slope parameters were not equal to zero. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 0.5% OPC-12759 0.5% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks | 72 |
| 1% OPC-12759 1% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks | 72 |
| 2% OPC-12759 2% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks | 74 |
| Placebo 0% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks | 72 |
| Total | 290 |
Baseline characteristics
| Characteristic | 0.5% OPC-12759 | 1% OPC-12759 | 2% OPC-12759 | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 33 Participants | 34 Participants | 27 Participants | 27 Participants | 121 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants | 38 Participants | 47 Participants | 45 Participants | 169 Participants |
| Age, Continuous | 60.3 years STANDARD_DEVIATION 13.6 | 62.5 years STANDARD_DEVIATION 13.5 | 60.3 years STANDARD_DEVIATION 11.5 | 56.0 years STANDARD_DEVIATION 16.2 | 59.8 years STANDARD_DEVIATION 13.9 |
| Region of Enrollment Japan | 72 participants | 72 participants | 74 participants | 72 participants | 290 participants |
| Sex: Female, Male Female | 66 Participants | 65 Participants | 70 Participants | 65 Participants | 266 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 4 Participants | 7 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 32 / 72 | 29 / 72 | 43 / 74 | 23 / 72 |
| serious Total, serious adverse events | 1 / 72 | 0 / 72 | 2 / 74 | 2 / 72 |
Outcome results
Primary
Change in Fluorescein Corneal Staining (FCS) Score From Baseline to Last Observation Carried Forward (LOCF)
FCS indicates the damage to the corneal epithelium. Per the National Eye Institute/Industry Workshop report, the cornea was divided into 5 fractions, each of which was given a staining score from 0 to 3, and the total score was calculated (0-15). 0 is better. The change from baseline (CFB) to LOCF at the end of instillation (LOCF endpoint) was used to analyze dose-response. A general linear model was used to examine if slope parameters were not equal to zero.
Time frame: baseline, 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.5% OPC-12759 | Change in Fluorescein Corneal Staining (FCS) Score From Baseline to Last Observation Carried Forward (LOCF) | -2.8 scores on a scale | Standard Deviation 2.3 |
| 1% OPC-12759 | Change in Fluorescein Corneal Staining (FCS) Score From Baseline to Last Observation Carried Forward (LOCF) | -3.1 scores on a scale | Standard Deviation 2.6 |
| 2% OPC-12759 | Change in Fluorescein Corneal Staining (FCS) Score From Baseline to Last Observation Carried Forward (LOCF) | -2.1 scores on a scale | Standard Deviation 2.8 |
| Placebo | Change in Fluorescein Corneal Staining (FCS) Score From Baseline to Last Observation Carried Forward (LOCF) | -2.6 scores on a scale | Standard Deviation 2.7 |
p-value: 0.385t-test, 2 sided
Primary
Change in Primary Ocular Discomfort (POD) Score From Baseline to Last Observation Carried Forward (LOCF)
POD indicates the ocular symptom most bothersome to the patient. POD selected by each patient from among the following ocular symptoms; Foreign body sensation, Dryness, Photophobia, Eye pain and Blurred vision. POD was scored from 0 through 4; a score of 0 indicated no symptoms and a score of 4 indicated very severe symptoms. 0 is better. The change from baseline (CFB) to LOCF at the end of instillation (LOCF endpoint) was used to analyze dose-response. A general linear model was used to examine if slope parameters were not equal to zero.
Time frame: Baseline, 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.5% OPC-12759 | Change in Primary Ocular Discomfort (POD) Score From Baseline to Last Observation Carried Forward (LOCF) | -1.2 scores on a scale | Standard Deviation 1.1 |
| 1% OPC-12759 | Change in Primary Ocular Discomfort (POD) Score From Baseline to Last Observation Carried Forward (LOCF) | -1.4 scores on a scale | Standard Deviation 1 |
| 2% OPC-12759 | Change in Primary Ocular Discomfort (POD) Score From Baseline to Last Observation Carried Forward (LOCF) | -1.3 scores on a scale | Standard Deviation 1.1 |
| Placebo | Change in Primary Ocular Discomfort (POD) Score From Baseline to Last Observation Carried Forward (LOCF) | -1.3 scores on a scale | Standard Deviation 0.9 |
p-value: 0.601t-test, 2 sided
Post Hoc
Change in Fluorescein Corneal Staining (FCS) Score From Baseline to Week 12
FCS indicates the damage to the corneal epithelium. Per the National Eye Institute/Industry Workshop report, the cornea was divided into 5 fractions, each of which was given a staining score from 0 to 3, and the total score was calculated (0-15). 0 is better. The CFB in the FCS scores were compared between the 0.5, 1 and 2% rebamipide group and the placebo group using a Dunnett's t-test
Time frame: Baseline, 12week
Population: From the FAS of 290 patients, 218 patients who had no punctal plug insertion or punctal occlusion and who had a baseline schirmer test value of equal to or less than 5 mm for the eye evaluated for efficacy were selected and subjected to exploratory data analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.5% OPC-12759 | Change in Fluorescein Corneal Staining (FCS) Score From Baseline to Week 12 | -3.2 scores on a scale | Standard Deviation 2.1 |
| 1% OPC-12759 | Change in Fluorescein Corneal Staining (FCS) Score From Baseline to Week 12 | -3.5 scores on a scale | Standard Deviation 2.4 |
| 2% OPC-12759 | Change in Fluorescein Corneal Staining (FCS) Score From Baseline to Week 12 | -2.9 scores on a scale | Standard Deviation 2.5 |
| Placebo | Change in Fluorescein Corneal Staining (FCS) Score From Baseline to Week 12 | -2.2 scores on a scale | Standard Deviation 2.6 |
p-value: 0.084t-test, 2 sided
p-value: 0.02t-test, 2 sided
p-value: 0.421t-test, 2 sided
Post Hoc
Change in Lissamine Green Conjunctival Staining (LGCS) Score From Baseline to Week 12
LGCS indicates the damage to the conjunctival epithelium. Per the National Eye Institute/Industry Workshop report, the conjunctiva was divided into 6 fractions, each of which was given a staining score from 0 to 3, and the total score was calculated (0-18). 0 is better. The CFB in the LGCS scores were compared between the 0.5, 1 and 2% rebamipide group and the placebo group using a Dunnett's t-test.
Time frame: Baseline, 12weeks
Population: From the FAS of 290 patients, 218 patients who had no punctal plug insertion or punctal occlusion and who had a baseline schirmer test value of equal to or less than 5 mm for the eye evaluated for efficacy were selected and subjected to exploratory data analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.5% OPC-12759 | Change in Lissamine Green Conjunctival Staining (LGCS) Score From Baseline to Week 12 | -3.8 scores on a scale | Standard Deviation 3.1 |
| 1% OPC-12759 | Change in Lissamine Green Conjunctival Staining (LGCS) Score From Baseline to Week 12 | -4.5 scores on a scale | Standard Deviation 3.3 |
| 2% OPC-12759 | Change in Lissamine Green Conjunctival Staining (LGCS) Score From Baseline to Week 12 | -4.2 scores on a scale | Standard Deviation 3.2 |
| Placebo | Change in Lissamine Green Conjunctival Staining (LGCS) Score From Baseline to Week 12 | -2.5 scores on a scale | Standard Deviation 3.2 |
p-value: 0.087t-test, 2 sided
p-value: 0.004t-test, 2 sided
p-value: 0.029t-test, 2 sided