Trial Outcomes & Findings for Dose-response Study of OPC-12759 Ophthalmic Suspension (NCT NCT00234078)

Last Updated: 2014-02-28

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

290 participants

Primary outcome timeframe

baseline, 12 weeks

Results posted on

2014-02-28

Participant Flow

Participant milestones

Participant milestones
Measure	0.5% OPC-12759 0.5% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	1% OPC-12759 1% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	2% OPC-12759 2% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	Placebo 0% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks
Overall Study STARTED	72	72	74	72
Overall Study COMPLETED	66	63	64	68
Overall Study NOT COMPLETED	6	9	10	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Dose-response Study of OPC-12759 Ophthalmic Suspension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	0.5% OPC-12759 n=72 Participants 0.5% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	1% OPC-12759 n=72 Participants 1% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	2% OPC-12759 n=74 Participants 2% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	Placebo n=72 Participants 0% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	Total n=290 Participants Total of all reporting groups
Age, Continuous	60.3 years STANDARD_DEVIATION 13.6 • n=5 Participants	62.5 years STANDARD_DEVIATION 13.5 • n=7 Participants	60.3 years STANDARD_DEVIATION 11.5 • n=5 Participants	56.0 years STANDARD_DEVIATION 16.2 • n=4 Participants	59.8 years STANDARD_DEVIATION 13.9 • n=21 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	39 Participants n=5 Participants	38 Participants n=7 Participants	47 Participants n=5 Participants	45 Participants n=4 Participants	169 Participants n=21 Participants
Age, Categorical >=65 years	33 Participants n=5 Participants	34 Participants n=7 Participants	27 Participants n=5 Participants	27 Participants n=4 Participants	121 Participants n=21 Participants
Sex: Female, Male Female	66 Participants n=5 Participants	65 Participants n=7 Participants	70 Participants n=5 Participants	65 Participants n=4 Participants	266 Participants n=21 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=4 Participants	24 Participants n=21 Participants
Region of Enrollment Japan	72 participants n=5 Participants	72 participants n=7 Participants	74 participants n=5 Participants	72 participants n=4 Participants	290 participants n=21 Participants

PRIMARY outcome

Timeframe: baseline, 12 weeks

Outcome measures

Outcome measures
Measure	0.5% OPC-12759 n=72 Participants 0.5% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	1% OPC-12759 n=72 Participants 1% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	2% OPC-12759 n=74 Participants 2% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	Placebo n=72 Participants 0% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks
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	-3.1 scores on a scale Standard Deviation 2.6	-2.1 scores on a scale Standard Deviation 2.8	-2.6 scores on a scale Standard Deviation 2.7

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	0.5% OPC-12759 n=72 Participants 0.5% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	1% OPC-12759 n=72 Participants 1% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	2% OPC-12759 n=74 Participants 2% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	Placebo n=74 Participants 0% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks
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	-1.4 scores on a scale Standard Deviation 1.0	-1.3 scores on a scale Standard Deviation 1.1	-1.3 scores on a scale Standard Deviation 0.9

POST_HOC outcome

Timeframe: 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

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

Outcome measures

Outcome measures
Measure	0.5% OPC-12759 n=56 Participants 0.5% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	1% OPC-12759 n=50 Participants 1% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	2% OPC-12759 n=46 Participants 2% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	Placebo n=51 Participants 0% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks
Change in Fluorescein Corneal Staining (FCS) Score From Baseline to Week 12	-3.2 scores on a scale Standard Deviation 2.1	-3.5 scores on a scale Standard Deviation 2.4	-2.9 scores on a scale Standard Deviation 2.5	-2.2 scores on a scale Standard Deviation 2.6

POST_HOC outcome

Timeframe: Baseline, 12weeks

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.

Outcome measures

Outcome measures
Measure	0.5% OPC-12759 n=56 Participants 0.5% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	1% OPC-12759 n=50 Participants 1% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	2% OPC-12759 n=46 Participants 2% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	Placebo n=51 Participants 0% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks
Change in Lissamine Green Conjunctival Staining (LGCS) Score From Baseline to Week 12	-3.8 scores on a scale Standard Deviation 3.1	-4.5 scores on a scale Standard Deviation 3.3	-4.2 scores on a scale Standard Deviation 3.2	-2.5 scores on a scale Standard Deviation 3.2

Adverse Events

0.5% OPC-12759

Serious events: 1 serious events

Other events: 32 other events

Deaths: 0 deaths

1% OPC-12759

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

2% OPC-12759

Serious events: 2 serious events

Other events: 43 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	0.5% OPC-12759 n=72 participants at risk 0.5% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	1% OPC-12759 n=72 participants at risk 1% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	2% OPC-12759 n=74 participants at risk 2% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	Placebo n=72 participants at risk 0% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks
Cardiac disorders Cardiac failure	0.00% 0/72 • 12 weeks	0.00% 0/72 • 12 weeks	0.00% 0/74 • 12 weeks	1.4% 1/72 • Number of events 1 • 12 weeks
Injury, poisoning and procedural complications Dislocation of joint prosthesis	0.00% 0/72 • 12 weeks	0.00% 0/72 • 12 weeks	1.4% 1/74 • Number of events 1 • 12 weeks	0.00% 0/72 • 12 weeks
Injury, poisoning and procedural complications Meniscus lesion	0.00% 0/72 • 12 weeks	0.00% 0/72 • 12 weeks	1.4% 1/74 • Number of events 1 • 12 weeks	0.00% 0/72 • 12 weeks
Musculoskeletal and connective tissue disorders Back pain	1.4% 1/72 • Number of events 1 • 12 weeks	0.00% 0/72 • 12 weeks	0.00% 0/74 • 12 weeks	0.00% 0/72 • 12 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm	0.00% 0/72 • 12 weeks	0.00% 0/72 • 12 weeks	0.00% 0/74 • 12 weeks	1.4% 1/72 • Number of events 1 • 12 weeks

Other adverse events

Other adverse events
Measure	0.5% OPC-12759 n=72 participants at risk 0.5% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	1% OPC-12759 n=72 participants at risk 1% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	2% OPC-12759 n=74 participants at risk 2% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks	Placebo n=72 participants at risk 0% rebamipide ophthalmic suspension received one drop of to both eyes four times a day for 12 weeks
Eye disorders Blepharitis	0.00% 0/72 • 12 weeks	0.00% 0/72 • 12 weeks	4.1% 3/74 • Number of events 3 • 12 weeks	1.4% 1/72 • Number of events 1 • 12 weeks
Eye disorders Eye discharge	2.8% 2/72 • Number of events 2 • 12 weeks	0.00% 0/72 • 12 weeks	4.1% 3/74 • Number of events 3 • 12 weeks	2.8% 2/72 • Number of events 2 • 12 weeks
Eye disorders Eye irritation	5.6% 4/72 • Number of events 4 • 12 weeks	2.8% 2/72 • Number of events 2 • 12 weeks	4.1% 3/74 • Number of events 3 • 12 weeks	4.2% 3/72 • Number of events 3 • 12 weeks
Eye disorders Eye pain	1.4% 1/72 • Number of events 1 • 12 weeks	2.8% 2/72 • Number of events 2 • 12 weeks	4.1% 3/74 • Number of events 3 • 12 weeks	1.4% 1/72 • Number of events 1 • 12 weeks
Eye disorders Eyelid oedema	0.00% 0/72 • 12 weeks	1.4% 1/72 • Number of events 1 • 12 weeks	4.1% 3/74 • Number of events 3 • 12 weeks	0.00% 0/72 • 12 weeks
Eye disorders Ocular hyperaemia	1.4% 1/72 • Number of events 1 • 12 weeks	1.4% 1/72 • Number of events 1 • 12 weeks	5.4% 4/74 • Number of events 4 • 12 weeks	2.8% 2/72 • Number of events 2 • 12 weeks
Eye disorders Eye pruritus	8.3% 6/72 • Number of events 6 • 12 weeks	5.6% 4/72 • Number of events 4 • 12 weeks	5.4% 4/74 • Number of events 4 • 12 weeks	1.4% 1/72 • Number of events 1 • 12 weeks
Infections and infestations Nasopharyngitis	20.8% 15/72 • Number of events 15 • 12 weeks	19.4% 14/72 • Number of events 14 • 12 weeks	17.6% 13/74 • Number of events 13 • 12 weeks	23.6% 17/72 • Number of events 17 • 12 weeks
Investigations Blood cholesterol increased	4.2% 3/72 • Number of events 3 • 12 weeks	1.4% 1/72 • Number of events 1 • 12 weeks	0.00% 0/74 • 12 weeks	0.00% 0/72 • 12 weeks
Nervous system disorders Dizziness	2.8% 2/72 • Number of events 2 • 12 weeks	4.2% 3/72 • Number of events 3 • 12 weeks	0.00% 0/74 • 12 weeks	0.00% 0/72 • 12 weeks
Nervous system disorders Dysgeusia (bitter taste)	15.3% 11/72 • Number of events 11 • 12 weeks	20.8% 15/72 • Number of events 15 • 12 weeks	25.7% 19/74 • Number of events 19 • 12 weeks	1.4% 1/72 • Number of events 1 • 12 weeks
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	4.2% 3/72 • Number of events 3 • 12 weeks	2.8% 2/72 • Number of events 2 • 12 weeks	1.4% 1/74 • Number of events 1 • 12 weeks	1.4% 1/72 • Number of events 1 • 12 weeks

Additional Information

Director of Clinical Research and Development

Otsuka Pharmaceutical Co., Ltd.

Phone: +81-3-6361-7366

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place