Confirmatory Study of OPC-12759 Ophthalmic Solution

• Sponsor: Otsuka Pharmaceutical Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01660256
• Collaborator: (none)
• Enrollment: 209
• Locations: 4
• Arms: 3
• Duration (Months): 9
• Patients Per Site: 52.3
• Patients Per Site Per Month: 5.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye	Drug: OPC-12759; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 209 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Confirmatory Study of OPC-12759 Ophthalmic Solution in Patients With Dry Eye
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OPC-12759 ophthalmic solution OPC-12759 ophthalmic solution	Drug: OPC-12759; Instillation, 4 times/day for 4 weeks; Other Names: rebamipide
Placebo Comparator: Placebo OPC-12759 ophthalmic solution 0%	Drug: Placebo
Active Comparator: OPC-12759 ophthalmic suspension OPC-12759 ophthalmic suspension	Drug: OPC-12759; Instillation, 4 times/day for 4 weeks; Other Names: rebamipide

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kansai Region	Kansai Region		Japan
2	Kanto region	Kanto Region		Japan
3	Kyushu region	Kyushu Region		Japan
4	Tokai region	Tokai Region		Japan

Sponsors and Collaborators

• Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Director: Eiji Murakami, Director of Division Dermatilogicals and Ophtalmolgicals, Otsuka Pharmaceutical Co., Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT01660256
• Other Study ID Numbers: 037E-11-003; JapicCTI-121920
• First Posted: Aug 8, 2012
• Last Update Posted: May 5, 2021
• Last Verified: Apr 1, 2021

• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Rebamipide

Study Results

Participant Flow

Arm/Group Title	OPC-12759 Solution	Placebo	OPC-12759 Suspension
Arm/Group Description	One drop of 2% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	One drop of 0% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	One drop of 2% OPC-12759 ophthalmic suspension was instilled into each eye 4 times a day for 4 weeks.
Period Title: Overall Study
STARTED	84	83	42
COMPLETED	79	83	38
NOT COMPLETED	5	0	4

Baseline Characteristics

Arm/Group Title	OPC-12759 Solution	Placebo	OPC-12759 Suspension	Total
Arm/Group Description	One drop of 2% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	One drop of 0% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	One drop of 2% OPC-12759 ophthalmic suspension was instilled into each eye 4 times a day for 4 weeks.	Total of all reporting groups
Overall Participants	84	83	42	209
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.7 (18.6)	56.5 (16.6)	54.2 (16.8)	56.5 (17.4)
Sex: Female, Male (Count of Participants)
Female	74 88.1%	67 80.7%	35 83.3%	176 84.2%
Male	10 11.9%	16 19.3%	7 16.7%	33 15.8%
Region of Enrollment (Count of Participants)
Japan	84 100%	83 100%	42 100%	209 100%

Outcome Measures

1. Primary Outcome

Title	Change in Fluorescein Corneal Staining (FCS) Score From Baseline
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set consisted of all subjects who had received the investigational product at least once after randomized assignment to a treatment group.

Arm/Group Title	OPC-12759 Solution	Placebo	OPC-12759 Suspension
Arm/Group Description	One drop of 2% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	One drop of 0% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	One drop of 2% OPC-12759 ophthalmic suspension was instilled into each eye 4 times a day for 4 weeks.
Measure Participants	84	83	42
Mean (Standard Error) [score on a scale]	-3.3 (0.2)	-2.0 (0.3)	-2.9 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OPC-12759 Solution, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in Lissamine Green Conjunctival Staining (LGCS) Score From Baseline
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set consisted of all subjects who had received the investigational product at least once after randomized assignment to a treatment group.

Arm/Group Title	OPC-12759 Solution	Placebo	OPC-12759 Suspension
Arm/Group Description	One drop of 2% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	One drop of 0% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	One drop of 2% OPC-12759 ophthalmic suspension was instilled into each eye 4 times a day for 4 weeks.
Measure Participants	84	83	42
Mean (Standard Error) [score on a scale]	-3.2 (0.3)	-1.7 (0.3)	-3.1 (0.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OPC-12759 Solution, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Treatment period (4 weeks)
Adverse Event Reporting Description	Only adverse events that occurred after the start of study treatment were evaluated. Safety analysis set consisted of all subjects who had received the investigational product at least once.
Arm/Group Title	OPC-12759 Solution		Placebo		OPC-12759 Suspension
Arm/Group Description	One drop of 2% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.		One drop of 0% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.		One drop of 2% OPC-12759 ophthalmic suspension was instilled into each eye 4 times a day for 4 weeks.
All Cause Mortality
	OPC-12759 Solution		Placebo		OPC-12759 Suspension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/84 (0%)		0/83 (0%)		0/42 (0%)
Serious Adverse Events
	OPC-12759 Solution		Placebo		OPC-12759 Suspension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/84 (0%)		0/83 (0%)		0/42 (0%)
Other (Not Including Serious) Adverse Events
	OPC-12759 Solution		Placebo		OPC-12759 Suspension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/84 (27.4%)		11/83 (13.3%)		11/42 (26.2%)
Eye disorders
Abnormal sensation in eye	1/84 (1.2%)		0/83 (0%)		1/42 (2.4%)
Eye irritation	0/84 (0%)		0/83 (0%)		1/42 (2.4%)
Ocular discomfort	1/84 (1.2%)		0/83 (0%)		0/42 (0%)
Ulcerative keratitis	1/84 (1.2%)		0/83 (0%)		0/42 (0%)
Gastrointestinal disorders
Abdominal pain	0/84 (0%)		1/83 (1.2%)		0/42 (0%)
Diarrhoea	1/84 (1.2%)		0/83 (0%)		0/42 (0%)
Mouth ulceration	0/84 (0%)		1/83 (1.2%)		0/42 (0%)
Periproctitis	0/84 (0%)		1/83 (1.2%)		0/42 (0%)
Infections and infestations
Adenoviral conjunctivitis	0/84 (0%)		0/83 (0%)		1/42 (2.4%)
Hordeolum	1/84 (1.2%)		0/83 (0%)		0/42 (0%)
Influenza	1/84 (1.2%)		0/83 (0%)		0/42 (0%)
Nasopharyngitis	1/84 (1.2%)		5/83 (6%)		1/42 (2.4%)
Investigations
Blood creatinine increased	0/84 (0%)		0/83 (0%)		1/42 (2.4%)
Blood urea increased	0/84 (0%)		0/83 (0%)		1/42 (2.4%)
Gamma-glutamyltransferase increased	1/84 (1.2%)		0/83 (0%)		0/42 (0%)
Glucose urine present	1/84 (1.2%)		0/83 (0%)		0/42 (0%)
White blood cell count increased	1/84 (1.2%)		0/83 (0%)		0/42 (0%)
Protein urine present	1/84 (1.2%)		0/83 (0%)		0/42 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenoma benign	0/84 (0%)		1/83 (1.2%)		0/42 (0%)
Nervous system disorders
Dysgeusia	13/84 (15.5%)		1/83 (1.2%)		5/42 (11.9%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation	1/84 (1.2%)		0/83 (0%)		0/42 (0%)
Skin and subcutaneous tissue disorders
Eczema	0/84 (0%)		1/83 (1.2%)		0/42 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.