Dry Eye
Conditions
Brief summary
The purpose of this study is to verify whether OPC-12759 ophthalmic solution is effective compared with placebo in dry eye patients. OPC-12759 ophthalmic suspension will be used as a reference drug.
Interventions
DRUGOPC-12759
Instillation, 4 times/day for 4 weeks
DRUGPlacebo
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Out patient 2. Subjective complaint of dry eye that has been present for minimum 20 months 3. Ocular discomfort severity is moderate to severe 4. Corneal - conjunctival damage is moderate to severe 5. Unanesthetized Schirmer's test score of 5mm/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 dry eye 2. Ocular hypertension patient or glaucoma patient with ophthalmic solution 3. Anticipated use of any topically-instilled ocular medications or patients who cannot discontinue the use during the study 4. Anticipated use of contact lens during the study 5. Patient with punctal plug 6. Any history of ocular surgery within 12 months 7. Female patients who are pregnant,possibly pregnant or breast feeding 8. Known hypersensitivity to any component of the study drug or procedural medications 9. Receipt of any investigational product within 4 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fluorescein Corneal Staining (FCS) Score From Baseline | Baseline, Week 4 | 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. Changes of the FCS score from baseline to the last dose (last observation carried forward \[LOCF\]) were compared between 2% OPC-12759 ophthalmic solution and placebo by the t-test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Lissamine Green Conjunctival Staining (LGCS) Score From Baseline | Baseline, Week 4 | 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 scores and change from baseline at each examination (including LOCF) were compared between 2% OPC-12759 ophthalmic solution and placebo ophthalmic solution. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OPC-12759 Solution One drop of 2% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks. | 84 |
| Placebo One drop of 0% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks. | 83 |
| OPC-12759 Suspension One drop of 2% OPC-12759 ophthalmic suspension was instilled into each eye 4 times a day for 4 weeks. | 42 |
| Total | 209 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | OPC-12759 Solution | Placebo | OPC-12759 Suspension | Total |
|---|---|---|---|---|
| Age, Continuous | 57.7 years STANDARD_DEVIATION 18.6 | 56.5 years STANDARD_DEVIATION 16.6 | 54.2 years STANDARD_DEVIATION 16.8 | 56.5 years STANDARD_DEVIATION 17.4 |
| Region of Enrollment Japan | 84 Participants | 83 Participants | 42 Participants | 209 Participants |
| Sex: Female, Male Female | 74 Participants | 67 Participants | 35 Participants | 176 Participants |
| Sex: Female, Male Male | 10 Participants | 16 Participants | 7 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 84 | 0 / 83 | 0 / 42 |
| other Total, other adverse events | 23 / 84 | 11 / 83 | 11 / 42 |
| serious Total, serious adverse events | 0 / 84 | 0 / 83 | 0 / 42 |
Outcome results
Primary
Change in Fluorescein Corneal Staining (FCS) Score From Baseline
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. Changes of the FCS score from baseline to the last dose (last observation carried forward \[LOCF\]) were compared between 2% OPC-12759 ophthalmic solution and placebo by the t-test.
Time frame: Baseline, Week 4
Population: Full analysis set consisted of all subjects who had received the investigational product at least once after randomized assignment to a treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-12759 Solution | Change in Fluorescein Corneal Staining (FCS) Score From Baseline | -3.3 score on a scale | Standard Error 0.2 |
| Placebo | Change in Fluorescein Corneal Staining (FCS) Score From Baseline | -2.0 score on a scale | Standard Error 0.3 |
| OPC-12759 Suspension | Change in Fluorescein Corneal Staining (FCS) Score From Baseline | -2.9 score on a scale | Standard Error 0.3 |
p-value: <0.001t-test, 2 sided
Secondary
Change in Lissamine Green Conjunctival Staining (LGCS) Score From Baseline
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 scores and change from baseline at each examination (including LOCF) were compared between 2% OPC-12759 ophthalmic solution and placebo ophthalmic solution.
Time frame: Baseline, Week 4
Population: Full analysis set consisted of all subjects who had received the investigational product at least once after randomized assignment to a treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OPC-12759 Solution | Change in Lissamine Green Conjunctival Staining (LGCS) Score From Baseline | -3.2 score on a scale | Standard Error 0.3 |
| Placebo | Change in Lissamine Green Conjunctival Staining (LGCS) Score From Baseline | -1.7 score on a scale | Standard Error 0.3 |
| OPC-12759 Suspension | Change in Lissamine Green Conjunctival Staining (LGCS) Score From Baseline | -3.1 score on a scale | Standard Error 0.4 |
p-value: <0.001t-test, 2 sided