Trial Outcomes & Findings for Confirmatory Study of OPC-12759 Ophthalmic Solution (NCT NCT01660256)

Last Updated: 2021-05-05

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. 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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

209 participants

Primary outcome timeframe

Baseline, Week 4

Results posted on

2021-05-05

Participant Flow

Participant milestones

Participant milestones
Measure	OPC-12759 Solution One drop of 2% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	Placebo One drop of 0% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	OPC-12759 Suspension One drop of 2% OPC-12759 ophthalmic suspension was instilled into each eye 4 times a day for 4 weeks.
Overall Study STARTED	84	83	42
Overall Study COMPLETED	79	83	38
Overall Study NOT COMPLETED	5	0	4

Reasons for withdrawal

Reasons for withdrawal
Measure	OPC-12759 Solution One drop of 2% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	Placebo One drop of 0% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	OPC-12759 Suspension One drop of 2% OPC-12759 ophthalmic suspension was instilled into each eye 4 times a day for 4 weeks.
Overall Study Adverse Event	4	0	2
Overall Study Withdrawal by Subject	1	0	2

Baseline Characteristics

Confirmatory Study of OPC-12759 Ophthalmic Solution

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OPC-12759 Solution n=84 Participants One drop of 2% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	Placebo n=83 Participants One drop of 0% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	OPC-12759 Suspension n=42 Participants One drop of 2% OPC-12759 ophthalmic suspension was instilled into each eye 4 times a day for 4 weeks.	Total n=209 Participants Total of all reporting groups
Age, Continuous	57.7 years STANDARD_DEVIATION 18.6 • n=5 Participants	56.5 years STANDARD_DEVIATION 16.6 • n=7 Participants	54.2 years STANDARD_DEVIATION 16.8 • n=5 Participants	56.5 years STANDARD_DEVIATION 17.4 • n=4 Participants
Sex: Female, Male Female	74 Participants n=5 Participants	67 Participants n=7 Participants	35 Participants n=5 Participants	176 Participants n=4 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	16 Participants n=7 Participants	7 Participants n=5 Participants	33 Participants n=4 Participants
Region of Enrollment Japan	84 Participants n=5 Participants	83 Participants n=7 Participants	42 Participants n=5 Participants	209 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	OPC-12759 Solution n=84 Participants One drop of 2% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	Placebo n=83 Participants One drop of 0% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	OPC-12759 Suspension n=42 Participants One drop of 2% OPC-12759 ophthalmic suspension was instilled into each eye 4 times a day for 4 weeks.
Change in Fluorescein Corneal Staining (FCS) Score From Baseline	-3.3 score on a scale Standard Error 0.2	-2.0 score on a scale Standard Error 0.3	-2.9 score on a scale Standard Error 0.3

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	OPC-12759 Solution n=84 Participants One drop of 2% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	Placebo n=83 Participants One drop of 0% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	OPC-12759 Suspension n=42 Participants One drop of 2% OPC-12759 ophthalmic suspension was instilled into each eye 4 times a day for 4 weeks.
Change in Lissamine Green Conjunctival Staining (LGCS) Score From Baseline	-3.2 score on a scale Standard Error 0.3	-1.7 score on a scale Standard Error 0.3	-3.1 score on a scale Standard Error 0.4

Adverse Events

OPC-12759 Solution

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

OPC-12759 Suspension

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Director of Clinical Trials

Otsuka Pharmaceutical Co., LTD.

Phone: +81-3-6361-7366

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	OPC-12759 Solution n=84 participants at risk One drop of 2% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	Placebo n=83 participants at risk One drop of 0% OPC-12759 ophthalmic solution was instilled into each eye 4 times a day for 4 weeks.	OPC-12759 Suspension n=42 participants at risk One drop of 2% OPC-12759 ophthalmic suspension was instilled into each eye 4 times a day for 4 weeks.
Eye disorders Abnormal sensation in eye	1.2% 1/84 • Treatment period (4 weeks) 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.	0.00% 0/83 • Treatment period (4 weeks) 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.	2.4% 1/42 • Treatment period (4 weeks) 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.
Eye disorders Eye irritation	0.00% 0/84 • Treatment period (4 weeks) 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.	0.00% 0/83 • Treatment period (4 weeks) 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.	2.4% 1/42 • Treatment period (4 weeks) 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.
Eye disorders Ocular discomfort	1.2% 1/84 • Treatment period (4 weeks) 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.	0.00% 0/83 • Treatment period (4 weeks) 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.	0.00% 0/42 • Treatment period (4 weeks) 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.
Eye disorders Ulcerative keratitis	1.2% 1/84 • Treatment period (4 weeks) 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.	0.00% 0/83 • Treatment period (4 weeks) 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.	0.00% 0/42 • Treatment period (4 weeks) 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.
Gastrointestinal disorders Abdominal pain	0.00% 0/84 • Treatment period (4 weeks) 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.	1.2% 1/83 • Treatment period (4 weeks) 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.	0.00% 0/42 • Treatment period (4 weeks) 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.
Gastrointestinal disorders Diarrhoea	1.2% 1/84 • Treatment period (4 weeks) 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.	0.00% 0/83 • Treatment period (4 weeks) 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.	0.00% 0/42 • Treatment period (4 weeks) 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.
Gastrointestinal disorders Mouth ulceration	0.00% 0/84 • Treatment period (4 weeks) 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.	1.2% 1/83 • Treatment period (4 weeks) 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.	0.00% 0/42 • Treatment period (4 weeks) 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.
Gastrointestinal disorders Periproctitis	0.00% 0/84 • Treatment period (4 weeks) 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.	1.2% 1/83 • Treatment period (4 weeks) 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.	0.00% 0/42 • Treatment period (4 weeks) 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.
Infections and infestations Adenoviral conjunctivitis	0.00% 0/84 • Treatment period (4 weeks) 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.	0.00% 0/83 • Treatment period (4 weeks) 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.	2.4% 1/42 • Treatment period (4 weeks) 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.
Infections and infestations Hordeolum	1.2% 1/84 • Treatment period (4 weeks) 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.	0.00% 0/83 • Treatment period (4 weeks) 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.	0.00% 0/42 • Treatment period (4 weeks) 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.
Infections and infestations Influenza	1.2% 1/84 • Treatment period (4 weeks) 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.	0.00% 0/83 • Treatment period (4 weeks) 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.	0.00% 0/42 • Treatment period (4 weeks) 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.
Infections and infestations Nasopharyngitis	1.2% 1/84 • Treatment period (4 weeks) 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.	6.0% 5/83 • Treatment period (4 weeks) 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.	2.4% 1/42 • Treatment period (4 weeks) 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.
Investigations Blood creatinine increased	0.00% 0/84 • Treatment period (4 weeks) 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.	0.00% 0/83 • Treatment period (4 weeks) 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.	2.4% 1/42 • Treatment period (4 weeks) 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.
Investigations Blood urea increased	0.00% 0/84 • Treatment period (4 weeks) 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.	0.00% 0/83 • Treatment period (4 weeks) 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.	2.4% 1/42 • Treatment period (4 weeks) 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.
Investigations Gamma-glutamyltransferase increased	1.2% 1/84 • Treatment period (4 weeks) 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.	0.00% 0/83 • Treatment period (4 weeks) 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.	0.00% 0/42 • Treatment period (4 weeks) 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.
Investigations Glucose urine present	1.2% 1/84 • Treatment period (4 weeks) 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.	0.00% 0/83 • Treatment period (4 weeks) 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.	0.00% 0/42 • Treatment period (4 weeks) 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.
Investigations White blood cell count increased	1.2% 1/84 • Treatment period (4 weeks) 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.	0.00% 0/83 • Treatment period (4 weeks) 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.	0.00% 0/42 • Treatment period (4 weeks) 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.
Investigations Protein urine present	1.2% 1/84 • Treatment period (4 weeks) 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.	0.00% 0/83 • Treatment period (4 weeks) 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.	0.00% 0/42 • Treatment period (4 weeks) 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenoma benign	0.00% 0/84 • Treatment period (4 weeks) 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.	1.2% 1/83 • Treatment period (4 weeks) 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.	0.00% 0/42 • Treatment period (4 weeks) 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.
Nervous system disorders Dysgeusia	15.5% 13/84 • Treatment period (4 weeks) 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.	1.2% 1/83 • Treatment period (4 weeks) 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.	11.9% 5/42 • Treatment period (4 weeks) 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.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	1.2% 1/84 • Treatment period (4 weeks) 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.	0.00% 0/83 • Treatment period (4 weeks) 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.	0.00% 0/42 • Treatment period (4 weeks) 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.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/84 • Treatment period (4 weeks) 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.	1.2% 1/83 • Treatment period (4 weeks) 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.	0.00% 0/42 • Treatment period (4 weeks) 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.