Late Phase 2 Study of OPC-12759 Ophthalmic Suspension

• Sponsor: Otsuka Pharmaceutical Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00475319
• Collaborator: (none)
• Enrollment: 308
• Locations: 6
• Arms: 3
• Duration (Months): 13
• Patients Per Site: 51.3
• Patients Per Site Per Month: 3.9

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the dose-response of OPC-12759 suspension in dry eye patients

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Syndromes	Drug: placebo; Drug: 1% OPC-12759 ophthalmic suspension; Drug: 2% OPC-12759 ophthalmic suspension	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 308 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Late Phase 2 Study of OPC-12759 Ophthalmic Suspension
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Jun 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo 0% OPC-12759 ophthalmic suspension received one drop to both eyes four times a day for 4 weeks.	Drug: placebo; comparison of different dosages of drug
Experimental: 1% OPC-12759 ophthalmic suspension 1% OPC-12759 ophthalmic suspension received one drop to both eyes four times a day for 4 weeks.	Drug: 1% OPC-12759 ophthalmic suspension; comparison of different dosages of drug
Experimental: 2% OPC-12759 ophthalmic suspension 2% OPC-12759 ophthalmic suspension received one drop to both eyes four times a day for 4 weeks.	Drug: 2% OPC-12759 ophthalmic suspension; comparison of different dosages of drug

Outcome Measures

Primary Outcome Measures

1. Change in Fluorescein Corneal Staining (FCS) Score From Baseline to Last Observation Carried Forward (LOCF) [Baseline, 4weeks]

   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.

Secondary Outcome Measures

1. Change in Lissamine Green Conjunctival Staining (LGCS) Score From Baseline to Last Observation Carried Forward (LOCF) [Baseline, 4weeks]

   LGCS indicates the damage to the conjunctival epithelium. Per the National Eye Institute/Industry Workshop report, the conjunctival sac and the conjunctina was divided into 6 ractions, 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 to each study time point was compared between the active-drug groups and the placebo group, and LOCF endpoint scores were used to compare the active-drug groups and the placebo group. In each treatment group, baseline scores and those obtained at each study time point were compared.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Outpatient

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 keratoconjunctivitis sicca

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		Chubu region		Japan
2		Kansai region		Japan
3		Kanto region		Japan
4		Kyushu region		Japan
5		Shikoku region		Japan
6		Tohoku region		Japan

Sponsors and Collaborators

• Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Director: Satoshi Oshima, Division of dermatologicals and ophthalmologicals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT00475319
• Other Study ID Numbers: 037E-06-001
• First Posted: May 21, 2007
• Last Update Posted: Jun 13, 2013
• Last Verified: May 1, 2013

• Keywords provided by Otsuka Pharmaceutical Co., Ltd.: Dry Eye Syndromes; OPC-12759
• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Rebamipide

Study Results

Participant Flow

Recruitment Details	Subjects were recruited in Japan between 2007 and 2008
Pre-assignment Detail	Participant flow results are based on the safety set.

Arm/Group Title	1% OPC-12759 Groups	2% OPC-12759 Groups	Placebo
Arm/Group Description	1% OPC-12759 ophthalmic suspension received one drop of to both eyes four times a day for 4 weeks	2% OPC-12759 ophthalmic suspension received one drop of to both eyes four times a day for 4 weeks	0% OPC-12759 ophthalmic suspension received one drop of to both eyes four times a day for 4 weeks
Period Title: Overall Study
STARTED	103	102	103
COMPLETED	101	101	99
NOT COMPLETED	2	1	4

Baseline Characteristics

Arm/Group Title	1% OPC-12759 Groups	2% OPC-12759 Groups	Placebo	Total
Arm/Group Description	1% OPC-12759 ophthalmic suspension received one drop of to both eyes four times a day for 4 weeks	2% OPC-12759 ophthalmic suspension received one drop of to both eyes four times a day for 4 weeks	0% OPC-12759 ophthalmic suspension received one drop of to both eyes four times a day for 4 weeks	Total of all reporting groups
Overall Participants	103	102	103	308
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	70 68%	61 59.8%	62 60.2%	193 62.7%
>=65 years	33 32%	41 40.2%	41 39.8%	115 37.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.7 (16.6)	56.3 (16.9)	55.6 (17.2)	55.2 (16.9)
Sex: Female, Male (Count of Participants)
Female	93 90.3%	86 84.3%	90 87.4%	269 87.3%
Male	10 9.7%	16 15.7%	13 12.6%	39 12.7%
Region of Enrollment (participants) [Number]
Japan	103 100%	102 100%	103 100%	308 100%

Outcome Measures

1. Primary Outcome

Title	Change in Fluorescein Corneal Staining (FCS) Score From Baseline to Last Observation Carried Forward (LOCF)
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.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, 4weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1% OPC-12759 Ophthalmic Suspension	2% OPC-12759 Ophthalmic Suspension	Placebo
Arm/Group Description	1% OPC-12759 ophthalmic suspension received one drop to both eyes four times a day for 4 weeks.	2% OPC-12759 ophthalmic suspension received one drop to both eyes four times a day for 4 weeks.	0% OPC-12759 ophthalmic suspension received one drop to both eyes four times a day for 4 weeks.
Measure Participants	103	102	103
Mean (Standard Deviation) [FCS score]	-3.5 (2.2)	-3.7 (2.4)	-1.8 (2.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1% OPC-12759 Ophthalmic Suspension, 2% OPC-12759 Ophthalmic Suspension, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	versus placebo
	Method	t-test, 2 sided
	Comments	a general linear model

2. Secondary Outcome

Title	Change in Lissamine Green Conjunctival Staining (LGCS) Score From Baseline to Last Observation Carried Forward (LOCF)
Description	LGCS indicates the damage to the conjunctival epithelium. Per the National Eye Institute/Industry Workshop report, the conjunctival sac and the conjunctina was divided into 6 ractions, 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 to each study time point was compared between the active-drug groups and the placebo group, and LOCF endpoint scores were used to compare the active-drug groups and the placebo group. In each treatment group, baseline scores and those obtained at each study time point were compared.
Time Frame	Baseline, 4weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1% OPC-12759 Groups	2% OPC-12759 Groups	Placebo
Arm/Group Description	1% OPC-12759 ophthalmic suspension received one drop of to both eyes four times a day for 4 weeks	2% OPC-12759 ophthalmic suspension received one drop of to both eyes four times a day for 4 weeks	0% OPC-12759 ophthalmic suspension received one drop of to both eyes four times a day for 4 weeks
Measure Participants	103	102	103
Mean (Standard Deviation) [LGCS score]	-4.0 (2.8)	-4.5 (2.9)	-1.9 (3.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1% OPC-12759 Ophthalmic Suspension, 2% OPC-12759 Ophthalmic Suspension, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	versus placebo
	Method	t-test, 2 sided
	Comments	a general linear model

Adverse Events

Arm/Group Title	1% OPC-12759 Groups		2% OPC-12759 Groups		Placebo
Arm/Group Description	1% OPC-12759 ophthalmic suspension received one drop of to both eyes four times a day for 4 weeks		2% OPC-12759 ophthalmic suspension received one drop of to both eyes four times a day for 4 weeks		0% OPC-12759 ophthalmic suspension received one drop of to both eyes four times a day for 4 weeks
All Cause Mortality
	1% OPC-12759 Groups		2% OPC-12759 Groups		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	1% OPC-12759 Groups		2% OPC-12759 Groups		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/103 (0%)		0/102 (0%)		1/103 (1%)
Respiratory, thoracic and mediastinal disorders
pneumonia	0/103 (0%)	0	0/102 (0%)	0	1/103 (1%)	1
Other (Not Including Serious) Adverse Events
	1% OPC-12759 Groups		2% OPC-12759 Groups		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/103 (29.1%)		31/102 (30.4%)		27/103 (26.2%)
Eye disorders
Abnormal sensation in eye	1/103 (1%)	1	0/102 (0%)	0	0/103 (0%)	0
Blepharitis	2/103 (1.9%)	2	1/102 (1%)	1	2/103 (1.9%)	2
Conjunctival haemorrhage	0/103 (0%)	0	1/102 (1%)	1	0/103 (0%)	0
Conjunctivitis	0/103 (0%)	0	0/102 (0%)	0	1/103 (1%)	1
Conjunctivitis allergic	1/103 (1%)	1	0/102 (0%)	0	0/103 (0%)	0
Corneal erosion	0/103 (0%)	0	1/102 (1%)	1	1/103 (1%)	1
Episcleritis	0/103 (0%)	0	0/102 (0%)	0	1/103 (1%)	1
Eye irritation	4/103 (3.9%)	4	2/102 (2%)	2	5/103 (4.9%)	5
Iritis	0/103 (0%)	0	0/102 (0%)	0	1/103 (1%)	1
Ocular hyperaemia	1/103 (1%)	1	0/102 (0%)	0	1/103 (1%)	1
Vision blurred	1/103 (1%)	1	1/102 (1%)	1	0/103 (0%)	0
Vitreous floaters	0/103 (0%)	0	0/102 (0%)	0	1/103 (1%)	1
Foreign body sensation in eyes	1/103 (1%)	1	0/102 (0%)	0	0/103 (0%)	0
Conjunctival hyperaemia	0/103 (0%)	0	2/102 (2%)	2	0/103 (0%)	0
Eyelids pruritus	1/103 (1%)	1	0/102 (0%)	0	0/103 (0%)	0
Eye pruritus	1/103 (1%)	1	1/102 (1%)	1	0/103 (0%)	0
Dacryostenosis acquired	0/103 (0%)	0	1/102 (1%)	1	0/103 (0%)	0
Ulcerative keratitis	0/103 (0%)	0	1/102 (1%)	1	0/103 (0%)	0
Gastrointestinal disorders
Dental caries	1/103 (1%)	1	0/102 (0%)	0	0/103 (0%)	0
Diarrhoea	0/103 (0%)	0	1/102 (1%)	1	0/103 (0%)	0
Nausea	1/103 (1%)	1	0/102 (0%)	0	0/103 (0%)	0
Vomiting	1/103 (1%)	1	0/102 (0%)	0	0/103 (0%)	0
General disorders
Oedema peripheral	1/103 (1%)	1	0/102 (0%)	0	0/103 (0%)	0
Pain	0/103 (0%)	0	0/102 (0%)	0	1/103 (1%)	1
Hepatobiliary disorders
Hepatic steatosis	0/103 (0%)	0	1/102 (1%)	1	0/103 (0%)	0
Infections and infestations
Bronchitis	0/103 (0%)	0	1/102 (1%)	1	0/103 (0%)	0
Cystitis	0/103 (0%)	0	0/102 (0%)	0	1/103 (1%)	1
Epiglottitis	0/103 (0%)	0	1/102 (1%)	1	0/103 (0%)	0
Nasopharyngitis	4/103 (3.9%)	4	3/102 (2.9%)	3	2/103 (1.9%)	2
Pharyngitis	0/103 (0%)	0	1/102 (1%)	1	0/103 (0%)	0
Tinea pedis	0/103 (0%)	0	1/102 (1%)	1	0/103 (0%)	0
Conjunctivitis bacterial	1/103 (1%)	1	0/102 (0%)	0	2/103 (1.9%)	2
Injury, poisoning and procedural complications
Joint sprain	1/103 (1%)	1	0/102 (0%)	0	0/103 (0%)	0
Investigations
Blood cholesterol increased	0/103 (0%)	0	0/102 (0%)	0	2/103 (1.9%)	2
Blood creatinine increased	0/103 (0%)	0	0/102 (0%)	0	1/103 (1%)	1
Blood potassium decreased	0/103 (0%)	0	0/102 (0%)	0	2/103 (1.9%)	2
Blood potassium increased	2/103 (1.9%)	2	0/102 (0%)	0	0/103 (0%)	0
Blood urea increased	1/103 (1%)	1	1/102 (1%)	1	0/103 (0%)	0
Gamma-glutamyltransferase increased	0/103 (0%)	0	0/102 (0%)	0	1/103 (1%)	1
Glucose urine present	0/103 (0%)	0	1/102 (1%)	1	0/103 (0%)	0
Platelet count decreased	0/103 (0%)	0	1/102 (1%)	1	0/103 (0%)	0
White blood cell count decreased	0/103 (0%)	0	2/102 (2%)	2	2/103 (1.9%)	2
Musculoskeletal and connective tissue disorders
Pain in extremity	0/103 (0%)	0	0/102 (0%)	0	1/103 (1%)	1
Nervous system disorders
Dizziness	1/103 (1%)	1	1/102 (1%)	1	0/103 (0%)	0
Dysgeusia	14/103 (13.6%)	14	16/102 (15.7%)	16	1/103 (1%)	1
Reproductive system and breast disorders
Breast pain	0/103 (0%)	0	0/102 (0%)	0	1/103 (1%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	0/103 (0%)	0	0/102 (0%)	0	1/103 (1%)	1
Tonsillar hypertrophy	0/103 (0%)	0	1/102 (1%)	1	0/103 (0%)	0
Rhinalgia	0/103 (0%)	0	1/102 (1%)	1	0/103 (0%)	0
Skin and subcutaneous tissue disorders
Urticaria	0/103 (0%)	0	0/102 (0%)	0	1/103 (1%)	1

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.