Phase 2 Extension Trial in Patients With Relapsing-Remitting Multiple Sclerosis (RRMS)

A Safety and Efficacy Extension Study of ONO-4641 (MSC2430913A) in Patients With Relapsing-Remitting Multiple Sclerosis

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01226745

Acronym

DreaMS

Enrollment

340

Registered

2010-10-22

Start date

2010-10-31

Completion date

2015-01-31

Last updated

2016-07-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Multiple Sclerosis

Keywords

Multiple sclerosis, ONO-4641, MSC2430913A, Efficacy

Brief summary

The objective of this active-drug Extension Study is to evaluate the continuing safety and efficacy of ONO-4641 (MSC2430913A) in subjects with relapsing-remitting multiple sclerosis (RRMS) who have completed an initial 26-week Core Study (ONO-4641POU006 \[NCT01081782\]).

Interventions

DRUGONO-4641

Subjects will be administered with ONO-4641 at a dose of 0.15 milligram (mg) in the core study will be administered with ONO-4641 0.15 mg in this extension study for a duration of 225 weeks.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Inclusion criteria

* Completed 26 weeks of double-blind phase of Study ONO-4641POU006

Exclusion criteria

* Presence of any dermatological abnormalities during Study ONO-4641POU006 that could increase the risk of the patient developing a skin cancer

Design outcomes

Primary

Measure	Time frame	Description
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	From the first dose of study drug administration up to 35 days after the last dose of study drug administration, assessed up to 5 years	An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A Serious Adverse Event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were defined as the AEs that occur between first dose of study drug administration and 35 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pretreatment state.
Number of Subjects With Clinically Significant Abnormal Electrocardiogram (ECG) Measures	Baseline up to Week 255	The 12-lead ECG was recorded after the subject was in supine position for 5 minutes. ECGs were acquired on digital cardiographs. Abnormal findings were analyzed as clinically significant or not clinically significant as per the discretion of the study investigator.
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	Baseline up to Week 255	Subjects underwent comprehensive ophthalmic examination (COE) including best corrected visual acuity (Snellen), manifest refractions, pupil examination, ocular motility, nystagmus, confrontation visual fields, Ishihara color plates, Amsler grid, and tonometry as well as a biomicroscopy slit lamp examination of the conjunctiva, cornea, anterior chamber, iris and lens; and a fundoscopic examination (with dilation) of the vitreous, optic nerve, retinal vessels, macula, and peripheral retina. Optical Coherence Tomography (OCT): Thicknesses of the macular retina and retinal nerve fiber layer at the optic nerve head in each eye was assessed by OCT using the fast macular thickness map scan and the fast retinal nerve fiber layer (RNFL) scan features, respectively. The abnormalities of the ophthalmologic examination was judged to be clinically significant or not as per the investigators discretion. The ophthalmologic examination was performed for both right eye (RE) and left eye (LE).
Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Baseline up to end of the treatment, assessed up to Week 255	A whole body examination, paying particular attention to identify precancerous or cancerous lesions was done by a dermatologist and based on the clinical judgment of the dermatologist the abnormalities were categorized as clinically significant or clinically not significant. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject early terminated from the study during the additional 2 year period with delay shall be defined.
Number of Subjects With Clinically Significant Abnormal Vital Signs	Baseline up to Week 255	Vital signs included oral temperature, pulse, respiration rate and blood pressure (BP) (taken after 5 minutes in the sitting position). The abnormalities in vital signs were decided as clinically significant or not based on the clinical judgment of the investigator.
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Baseline, Week 40, 52, 76, 100, 124, 148, early termination, Week 152, 200, early termination 2, Week 255	FEV1 was defined as the maximal volume of air exhaled in the 1st second of a forced expiration from a position of full inspiration. FEV1 was obtained from spirometry, performed before study treatment administration. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject early terminated from the study during the additional 2 year period with delay shall be defined.
Change From Baseline in Forced Vital Capacity (FVC)	Baseline, Week 40, 52, 76, 100, 124, 148, early termination, Week 152, 200, early termination 2, Week 255	FVC (% of predicted value) was the volume of air which was forcibly exhaled from the lungs after taking the deepest breath possible. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject early terminated from the study during the additional 2 year period with delay shall be defined.
Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Baseline, Week 40, 52, early termination, Week 152, 200, 255	DLCO was one of the most clinically valuable tests of lung function. The DLCO measure the ability of the lungs to transfer gas from inhaled air to the red blood cells in pulmonary capillaries. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject was early terminated from the study during the additional 2 year period with delay. The values for the DLCO % of predicted was defined as the mean value of 2 test results that were within a 10% variability of each other.

Secondary

Measure	Time frame	Description
Change From Baseline in Lesion Volume at the End of the Treatment (EoT)	Baseline, End of treatment (5 years)	Brain lesion volume was obtained by magnetic resonance imaging (MRI). Extension study baseline was defined as the measurement most immediately prior to or on the day of the first dose day of extension study. End of treatment (EOT) was defined as the last visit during the treatment period. Change from extension baseline to EOT = last treatment period value in extension study - extension baseline value.
Percent Brain Volume Change (PBVC) From Baseline at the End of Treatment	Baseline and at end of treatment (Week 255)	Brain volume was obtained by magnetic resonance imaging (MRI). Extension study baseline is defined as the measurement most immediately prior to or on the day of the first dose day of extension study. Brain volume changes very little over time. Hence, the PBVC at the end of treatment was calculated by adding up all the PBVC values from the scans performed during the extension treatment period.
Number of Gadolinium (Gd)-Enhanced Lesions	Baseline, Week 40, 52, 100, 148, early termination, Week 152, 200, early termination 2, Week 255 and end of treatment (5 years)	Gd-enhanced lesions were obtained by magnetic resonance imaging (MRI) at each scheduled assessment visit over the study period. Extension study baseline is defined as the measurement most immediately prior to or on the day of the first dose day of extension study. End of treatment (EoT) lesion count is the average number of lesion counts per scan, calculated by dividing the sum of all lesion counts by number of scans during the extension treatment period. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject early terminated from the study during the additional 2 year period with delay. Extension study baseline is defined as the measurement most immediately prior to or on the day of the first dose day of extension study.Full Analysis Set (FAS) included all subjects who provided any post baseline efficacy data.

Countries

Belgium, Canada, Czechia, Germany, Greece, Japan, Poland, Russia, Spain, Ukraine, United States

Participant flow

Pre-assignment details

One Subject received 0.15 mg of ONO-4641 instead of placebo in error in the core trial and was subsequently re-randomized during the extension trial and received 0.10 mg of ONO-4641.This subject was not reported in the participant flow for the study.

Participants by arm

Arm	Count
ONO-4641 0.15 mg - 0.15 mg Subjects who were administered with ONO-4641 at a dose of 0.15 mg in the core study were administered with ONO-4641 at a dose of 0.15 mg once daily in the extension study for a duration of 225 weeks.	80
ONO-4641 0.10 mg - 0.10 mg Subjects who were administered with ONO-4641 at a dose of 0.10 mg in the core study were administered with ONO-4641 at a dose of 0.10 mg once daily in the extension study for a duration of 225 weeks.	87
ONO-4641 0.05 mg - 0.05 mg Subjects who were administered with ONO-4641 at a dose of 0.05 mg in the core study were administered with ONO-4641 at a dose of 0.05 mg once daily in the extension study for a duration of 225 weeks.	89
Placebo - ONO4641 0.15 mg Subjects who were administered with placebo in the core study were administered with ONO-4641 at a dose of 0.15 mg once daily in the extension study for a duration of 225 weeks.	29
Placebo - ONO4641 0.10 mg Subjects who were administered with placebo in the core study were administered with ONO-4641 at a dose of 0.10 mg once daily in the extension study for a duration of 225 weeks.	26
Placebo - ONO4641 0.05 mg Subjects who were administered with placebo in the core study were administered with ONO-4641 at a dose of 0.05 mg once daily in the extension study for a duration of 225 weeks.	29
Total	340

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005
Overall Study	Death	1	0	0	0	0	1
Overall Study	Did not complete schedule of assessments	8	3	6	0	0	1
Overall Study	Lost to Follow-up	2	6	6	1	1	2
Overall Study	Other	6	7	8	4	3	1

Baseline characteristics

Characteristic	ONO-4641 0.15 mg - 0.15 mg	ONO-4641 0.10 mg - 0.10 mg	ONO-4641 0.05 mg - 0.05 mg	Placebo - ONO4641 0.15 mg	Placebo - ONO4641 0.10 mg	Placebo - ONO4641 0.05 mg	Total
Age, Continuous	36.3 Years STANDARD_DEVIATION 8.47	36.0 Years STANDARD_DEVIATION 8.64	38.2 Years STANDARD_DEVIATION 8.66	35.6 Years STANDARD_DEVIATION 9.59	37.0 Years STANDARD_DEVIATION 6.96	38.7 Years STANDARD_DEVIATION 9.48	36.9 Years STANDARD_DEVIATION 8.66
Sex: Female, Male Female	53 Participants	74 Participants	66 Participants	18 Participants	17 Participants	24 Participants	252 Participants
Sex: Female, Male Male	27 Participants	13 Participants	23 Participants	11 Participants	9 Participants	5 Participants	88 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	67 / 80	80 / 87	72 / 89	21 / 29	21 / 26	27 / 29
serious Total, serious adverse events	16 / 80	12 / 87	21 / 89	5 / 29	9 / 26	11 / 29

Outcome results

Primary

Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)

DLCO was one of the most clinically valuable tests of lung function. The DLCO measure the ability of the lungs to transfer gas from inhaled air to the red blood cells in pulmonary capillaries. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject was early terminated from the study during the additional 2 year period with delay. The values for the DLCO % of predicted was defined as the mean value of 2 test results that were within a 10% variability of each other.

Time frame: Baseline, Week 40, 52, early termination, Week 152, 200, 255

Population: Safety analysis set consisted of all the enrolled subjects. Here n signifies the number of subjects analyzed for the individual time point in the outcome measure.

Arm	Measure	Group	Value (MEAN)	Dispersion
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 40 (n=22, 21, 16, 8, 9, 4)	2.4 Percentage of predicted value	Standard Deviation 13.16
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 52 (n=20, 19, 19, 8, 9, 5)	-3.7 Percentage of predicted value	Standard Deviation 8.36
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Early termination (n=2, 1, 2, 3, 0, 0)	-6.5 Percentage of predicted value	Standard Deviation 2.12
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 152 (n=3, 1, 2, 1, 0, 0)	-1.0 Percentage of predicted value	Standard Deviation 1
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 200 (n=7, 5, 5, 2, 3, 2)	3.0 Percentage of predicted value	Standard Deviation 43.89
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 255 (n=14, 15, 12, 4, 6, 4)	42.3 Percentage of predicted value	Standard Deviation 40.41
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 52 (n=20, 19, 19, 8, 9, 5)	-2.7 Percentage of predicted value	Standard Deviation 10.74
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 152 (n=3, 1, 2, 1, 0, 0)	11.0 Percentage of predicted value	—
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 255 (n=14, 15, 12, 4, 6, 4)	21.0 Percentage of predicted value	Standard Deviation 29.4
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 40 (n=22, 21, 16, 8, 9, 4)	-1.0 Percentage of predicted value	Standard Deviation 10.98
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Early termination (n=2, 1, 2, 3, 0, 0)	-9.0 Percentage of predicted value	—
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 200 (n=7, 5, 5, 2, 3, 2)	2.0 Percentage of predicted value	Standard Deviation 12.85
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 255 (n=14, 15, 12, 4, 6, 4)	27.8 Percentage of predicted value	Standard Deviation 37.38
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 200 (n=7, 5, 5, 2, 3, 2)	35.8 Percentage of predicted value	Standard Deviation 34.87
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 152 (n=3, 1, 2, 1, 0, 0)	9.5 Percentage of predicted value	Standard Deviation 3.54
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Early termination (n=2, 1, 2, 3, 0, 0)	-43.0 Percentage of predicted value	Standard Deviation 46.67
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 40 (n=22, 21, 16, 8, 9, 4)	-2.4 Percentage of predicted value	Standard Deviation 17.36
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 52 (n=20, 19, 19, 8, 9, 5)	0.8 Percentage of predicted value	Standard Deviation 20.01
Placebo - ONO4641 0.15 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 152 (n=3, 1, 2, 1, 0, 0)	-14.0 Percentage of predicted value	—
Placebo - ONO4641 0.15 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 52 (n=20, 19, 19, 8, 9, 5)	-5.3 Percentage of predicted value	Standard Deviation 11.56
Placebo - ONO4641 0.15 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Early termination (n=2, 1, 2, 3, 0, 0)	-16.3 Percentage of predicted value	Standard Deviation 12.58
Placebo - ONO4641 0.15 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 255 (n=14, 15, 12, 4, 6, 4)	5.8 Percentage of predicted value	Standard Deviation 32.79
Placebo - ONO4641 0.15 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 200 (n=7, 5, 5, 2, 3, 2)	9.5 Percentage of predicted value	Standard Deviation 28.99
Placebo - ONO4641 0.15 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 40 (n=22, 21, 16, 8, 9, 4)	-5.3 Percentage of predicted value	Standard Deviation 16.02
Placebo - ONO4641 0.10 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 40 (n=22, 21, 16, 8, 9, 4)	-2.7 Percentage of predicted value	Standard Deviation 10.61
Placebo - ONO4641 0.10 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 200 (n=7, 5, 5, 2, 3, 2)	25.0 Percentage of predicted value	Standard Deviation 12
Placebo - ONO4641 0.10 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 52 (n=20, 19, 19, 8, 9, 5)	-4.8 Percentage of predicted value	Standard Deviation 8.04
Placebo - ONO4641 0.10 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Early termination (n=2, 1, 2, 3, 0, 0)	NA Percentage of predicted value	—
Placebo - ONO4641 0.10 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 152 (n=3, 1, 2, 1, 0, 0)	NA Percentage of predicted value	—
Placebo - ONO4641 0.10 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 255 (n=14, 15, 12, 4, 6, 4)	37.5 Percentage of predicted value	Standard Deviation 40.78
Placebo - ONO4641 0.05 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 152 (n=3, 1, 2, 1, 0, 0)	NA Percentage of predicted value	—
Placebo - ONO4641 0.05 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Early termination (n=2, 1, 2, 3, 0, 0)	NA Percentage of predicted value	—
Placebo - ONO4641 0.05 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 200 (n=7, 5, 5, 2, 3, 2)	5.0 Percentage of predicted value	Standard Deviation 9.9
Placebo - ONO4641 0.05 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 255 (n=14, 15, 12, 4, 6, 4)	16.3 Percentage of predicted value	Standard Deviation 19.52
Placebo - ONO4641 0.05 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 52 (n=20, 19, 19, 8, 9, 5)	5.2 Percentage of predicted value	Standard Deviation 6.34
Placebo - ONO4641 0.05 mg	Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)	Week 40 (n=22, 21, 16, 8, 9, 4)	3.3 Percentage of predicted value	Standard Deviation 6.4

Primary

Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)

FEV1 was defined as the maximal volume of air exhaled in the 1st second of a forced expiration from a position of full inspiration. FEV1 was obtained from spirometry, performed before study treatment administration. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject early terminated from the study during the additional 2 year period with delay shall be defined.

Time frame: Baseline, Week 40, 52, 76, 100, 124, 148, early termination, Week 152, 200, early termination 2, Week 255

Population: Safety analysis set consisted of all the enrolled subjects. Here n signifies the number of subjects analyzed for the individual time point in the outcome measure.

Arm	Measure	Group	Value (MEAN)	Dispersion
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Early termination (n=16, 17, 13, 7, 3, 8)	-6.803 Percentage of predicted value	Standard Deviation 6.7393
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 124 (n=66, 70, 68, 21, 23, 18)	-0.795 Percentage of predicted value	Standard Deviation 9.6531
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 255 (n=47, 48, 47, 17, 16, 13)	-0.368 Percentage of predicted value	Standard Deviation 13.5515
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 200 (n=18, 18, 19, 6, 6, 3)	-0.024 Percentage of predicted value	Standard Deviation 8.0705
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 148 (n=59, 67, 68, 20, 21, 18)	-1.828 Percentage of predicted value	Standard Deviation 10.8131
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 52 (n=74, 84, 77, 25, 24, 21)	-0.675 Percentage of predicted value	Standard Deviation 7.7166
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 40 (n=77, 83, 82, 29, 24, 24)	-0.227 Percentage of predicted value	Standard Deviation 6.5379
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 76 (n=72, 78, 74, 24, 24, 21)	1.148 Percentage of predicted value	Standard Deviation 9.595
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 100 (n=68, 70, 72, 24, 24, 18)	-0.746 Percentage of predicted value	Standard Deviation 8.3955
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 152 (n=12, 12, 10, 4, 3, 8)	-3.786 Percentage of predicted value	Standard Deviation 7.3297
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Early termination 2(n=56, 63, 63, 19, 20, 16)	-1.416 Percentage of predicted value	Standard Deviation 9.4274
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Early termination 2(n=56, 63, 63, 19, 20, 16)	-2.031 Percentage of predicted value	Standard Deviation 10.6185
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Early termination (n=16, 17, 13, 7, 3, 8)	0.443 Percentage of predicted value	Standard Deviation 6.084
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 100 (n=68, 70, 72, 24, 24, 18)	-2.790 Percentage of predicted value	Standard Deviation 8.2129
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 124 (n=66, 70, 68, 21, 23, 18)	-2.003 Percentage of predicted value	Standard Deviation 7.7998
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 76 (n=72, 78, 74, 24, 24, 21)	-2.352 Percentage of predicted value	Standard Deviation 6.1152
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 255 (n=47, 48, 47, 17, 16, 13)	-1.374 Percentage of predicted value	Standard Deviation 11.092
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 200 (n=18, 18, 19, 6, 6, 3)	-0.354 Percentage of predicted value	Standard Deviation 12.8489
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 152 (n=12, 12, 10, 4, 3, 8)	4.515 Percentage of predicted value	Standard Deviation 11.3809
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 40 (n=77, 83, 82, 29, 24, 24)	-0.741 Percentage of predicted value	Standard Deviation 6.2026
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 148 (n=59, 67, 68, 20, 21, 18)	-3.429 Percentage of predicted value	Standard Deviation 8.4036
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 52 (n=74, 84, 77, 25, 24, 21)	-1.981 Percentage of predicted value	Standard Deviation 6.8499
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 148 (n=59, 67, 68, 20, 21, 18)	-1.234 Percentage of predicted value	Standard Deviation 6.527
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 152 (n=12, 12, 10, 4, 3, 8)	-1.725 Percentage of predicted value	Standard Deviation 7.4166
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Early termination (n=16, 17, 13, 7, 3, 8)	-1.780 Percentage of predicted value	Standard Deviation 11.6068
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 52 (n=74, 84, 77, 25, 24, 21)	-0.484 Percentage of predicted value	Standard Deviation 6.0952
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 40 (n=77, 83, 82, 29, 24, 24)	-0.062 Percentage of predicted value	Standard Deviation 5.4947
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 76 (n=72, 78, 74, 24, 24, 21)	0.650 Percentage of predicted value	Standard Deviation 7.2084
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Early termination 2(n=56, 63, 63, 19, 20, 16)	-2.859 Percentage of predicted value	Standard Deviation 9.6661
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 100 (n=68, 70, 72, 24, 24, 18)	-1.187 Percentage of predicted value	Standard Deviation 7.8818
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 255 (n=47, 48, 47, 17, 16, 13)	-0.027 Percentage of predicted value	Standard Deviation 13.0574
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 200 (n=18, 18, 19, 6, 6, 3)	-2.144 Percentage of predicted value	Standard Deviation 8.3421
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 124 (n=66, 70, 68, 21, 23, 18)	0.197 Percentage of predicted value	Standard Deviation 7.9068
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Early termination 2(n=56, 63, 63, 19, 20, 16)	-1.321 Percentage of predicted value	Standard Deviation 8.7759
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 40 (n=77, 83, 82, 29, 24, 24)	-1.500 Percentage of predicted value	Standard Deviation 5.0115
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 52 (n=74, 84, 77, 25, 24, 21)	-3.113 Percentage of predicted value	Standard Deviation 5.4753
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 76 (n=72, 78, 74, 24, 24, 21)	-1.574 Percentage of predicted value	Standard Deviation 6.3645
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 100 (n=68, 70, 72, 24, 24, 18)	-3.202 Percentage of predicted value	Standard Deviation 6.7073
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 124 (n=66, 70, 68, 21, 23, 18)	-2.178 Percentage of predicted value	Standard Deviation 9.7656
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 148 (n=59, 67, 68, 20, 21, 18)	-0.459 Percentage of predicted value	Standard Deviation 9.0302
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Early termination (n=16, 17, 13, 7, 3, 8)	-2.984 Percentage of predicted value	Standard Deviation 13.8177
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 152 (n=12, 12, 10, 4, 3, 8)	-11.929 Percentage of predicted value	Standard Deviation 13.1156
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 200 (n=18, 18, 19, 6, 6, 3)	-2.299 Percentage of predicted value	Standard Deviation 8.2038
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 255 (n=47, 48, 47, 17, 16, 13)	-0.209 Percentage of predicted value	Standard Deviation 12.1999
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 152 (n=12, 12, 10, 4, 3, 8)	-11.525 Percentage of predicted value	Standard Deviation 12.3316
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 76 (n=72, 78, 74, 24, 24, 21)	-2.300 Percentage of predicted value	Standard Deviation 9.2869
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 255 (n=47, 48, 47, 17, 16, 13)	-2.377 Percentage of predicted value	Standard Deviation 11.6511
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Early termination 2(n=56, 63, 63, 19, 20, 16)	-1.291 Percentage of predicted value	Standard Deviation 10.4528
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 200 (n=18, 18, 19, 6, 6, 3)	-4.557 Percentage of predicted value	Standard Deviation 13.3731
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 52 (n=74, 84, 77, 25, 24, 21)	-2.851 Percentage of predicted value	Standard Deviation 6.7997
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 124 (n=66, 70, 68, 21, 23, 18)	-1.968 Percentage of predicted value	Standard Deviation 9.2415
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 40 (n=77, 83, 82, 29, 24, 24)	-1.555 Percentage of predicted value	Standard Deviation 7.8424
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 100 (n=68, 70, 72, 24, 24, 18)	-3.748 Percentage of predicted value	Standard Deviation 8.5817
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Early termination (n=16, 17, 13, 7, 3, 8)	-4.109 Percentage of predicted value	Standard Deviation 21.4354
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 148 (n=59, 67, 68, 20, 21, 18)	-3.052 Percentage of predicted value	Standard Deviation 9.497
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 148 (n=59, 67, 68, 20, 21, 18)	-2.599 Percentage of predicted value	Standard Deviation 10.3997
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 255 (n=47, 48, 47, 17, 16, 13)	-0.963 Percentage of predicted value	Standard Deviation 14.2975
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 152 (n=12, 12, 10, 4, 3, 8)	2.688 Percentage of predicted value	Standard Deviation 5.5468
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 124 (n=66, 70, 68, 21, 23, 18)	-0.874 Percentage of predicted value	Standard Deviation 8.2237
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 100 (n=68, 70, 72, 24, 24, 18)	-1.207 Percentage of predicted value	Standard Deviation 7.74
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 200 (n=18, 18, 19, 6, 6, 3)	0.944 Percentage of predicted value	Standard Deviation 7.8955
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 76 (n=72, 78, 74, 24, 24, 21)	2.657 Percentage of predicted value	Standard Deviation 8.928
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 52 (n=74, 84, 77, 25, 24, 21)	-0.561 Percentage of predicted value	Standard Deviation 5.504
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Early termination 2(n=56, 63, 63, 19, 20, 16)	-3.249 Percentage of predicted value	Standard Deviation 11.5213
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Week 40 (n=77, 83, 82, 29, 24, 24)	-1.146 Percentage of predicted value	Standard Deviation 4.7952
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)	Early termination (n=16, 17, 13, 7, 3, 8)	2.108 Percentage of predicted value	Standard Deviation 8.1682

Primary

Change From Baseline in Forced Vital Capacity (FVC)

FVC (% of predicted value) was the volume of air which was forcibly exhaled from the lungs after taking the deepest breath possible. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject early terminated from the study during the additional 2 year period with delay shall be defined.

Time frame: Baseline, Week 40, 52, 76, 100, 124, 148, early termination, Week 152, 200, early termination 2, Week 255

Population: Safety analysis set consisted of all the enrolled subjects. Here n signifies the number of subjects analyzed for the individual time point in the outcome measure

Arm	Measure	Group	Value (MEAN)	Dispersion
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Early termination(n=16, 17, 13, 7, 3, 8)	-4.225 Percentage of predicted value	Standard Deviation 8.2667
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 124 (n=66, 70, 68, 21, 23, 18)	-0.794 Percentage of predicted value	Standard Deviation 7.8392
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 255 (n=47, 48, 47, 17, 16, 13)	-0.717 Percentage of predicted value	Standard Deviation 8.1437
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 200 (n=18, 18, 19, 6, 6, 3)	-0.316 Percentage of predicted value	Standard Deviation 5.0212
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 148 (n=59, 67, 68, 20, 21, 18)	-0.909 Percentage of predicted value	Standard Deviation 6.7009
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 52 (n=74, 84, 77, 25, 24, 21)	-0.681 Percentage of predicted value	Standard Deviation 6.1396
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 40 (n=77,83,82,29,24,24)	-0.123 Percentage of predicted value	Standard Deviation 6.9868
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 76 (n=72, 78, 74, 24, 24, 21)	1.397 Percentage of predicted value	Standard Deviation 8.1634
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 100 (n=68, 70, 72, 24, 24, 18)	-0.308 Percentage of predicted value	Standard Deviation 7.9759
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 152 (n=12, 12, 10, 4, 3, 8)	-4.256 Percentage of predicted value	Standard Deviation 7.4403
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Early termination (n=56, 63, 63, 19, 20, 16)	-0.033 Percentage of predicted value	Standard Deviation 6.5169
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Early termination (n=56, 63, 63, 19, 20, 16)	-1.952 Percentage of predicted value	Standard Deviation 9.6157
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Early termination(n=16, 17, 13, 7, 3, 8)	-0.632 Percentage of predicted value	Standard Deviation 5.1482
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 100 (n=68, 70, 72, 24, 24, 18)	-2.433 Percentage of predicted value	Standard Deviation 6.678
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 124 (n=66, 70, 68, 21, 23, 18)	-2.246 Percentage of predicted value	Standard Deviation 6.5967
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 76 (n=72, 78, 74, 24, 24, 21)	-1.906 Percentage of predicted value	Standard Deviation 6.0432
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 255 (n=47, 48, 47, 17, 16, 13)	-1.686 Percentage of predicted value	Standard Deviation 10.456
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 200 (n=18, 18, 19, 6, 6, 3)	-3.057 Percentage of predicted value	Standard Deviation 12.0551
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 152 (n=12, 12, 10, 4, 3, 8)	-0.074 Percentage of predicted value	Standard Deviation 6.8982
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 40 (n=77,83,82,29,24,24)	-1.000 Percentage of predicted value	Standard Deviation 6.406
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 148 (n=59, 67, 68, 20, 21, 18)	-3.078 Percentage of predicted value	Standard Deviation 6.6149
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 52 (n=74, 84, 77, 25, 24, 21)	-1.175 Percentage of predicted value	Standard Deviation 6.1523
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 148 (n=59, 67, 68, 20, 21, 18)	0.124 Percentage of predicted value	Standard Deviation 7.7589
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 152 (n=12, 12, 10, 4, 3, 8)	-2.829 Percentage of predicted value	Standard Deviation 7.0313
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Early termination(n=16, 17, 13, 7, 3, 8)	979.704 Percentage of predicted value	Standard Deviation 3533.9625
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 52 (n=74, 84, 77, 25, 24, 21)	0.107 Percentage of predicted value	Standard Deviation 7.7364
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 40 (n=77,83,82,29,24,24)	0.921 Percentage of predicted value	Standard Deviation 6.9931
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 76 (n=72, 78, 74, 24, 24, 21)	1.828 Percentage of predicted value	Standard Deviation 10.0612
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Early termination (n=56, 63, 63, 19, 20, 16)	-0.903 Percentage of predicted value	Standard Deviation 10.0341
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 100 (n=68, 70, 72, 24, 24, 18)	0.118 Percentage of predicted value	Standard Deviation 7.8025
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 255 (n=47, 48, 47, 17, 16, 13)	1.386 Percentage of predicted value	Standard Deviation 13.997
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 200 (n=18, 18, 19, 6, 6, 3)	-1.590 Percentage of predicted value	Standard Deviation 8.9426
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 124 (n=66, 70, 68, 21, 23, 18)	0.890 Percentage of predicted value	Standard Deviation 7.8545
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Early termination (n=56, 63, 63, 19, 20, 16)	-1.593 Percentage of predicted value	Standard Deviation 8.6842
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 40 (n=77,83,82,29,24,24)	-1.593 Percentage of predicted value	Standard Deviation 5.052
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 52 (n=74, 84, 77, 25, 24, 21)	-2.690 Percentage of predicted value	Standard Deviation 5.2847
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 76 (n=72, 78, 74, 24, 24, 21)	-2.487 Percentage of predicted value	Standard Deviation 6.583
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 100 (n=68, 70, 72, 24, 24, 18)	-2.683 Percentage of predicted value	Standard Deviation 4.987
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 124 (n=66, 70, 68, 21, 23, 18)	-2.582 Percentage of predicted value	Standard Deviation 8.464
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 148 (n=59, 67, 68, 20, 21, 18)	-2.010 Percentage of predicted value	Standard Deviation 7.8162
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Early termination(n=16, 17, 13, 7, 3, 8)	0.278 Percentage of predicted value	Standard Deviation 9.2002
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 152 (n=12, 12, 10, 4, 3, 8)	-3.748 Percentage of predicted value	Standard Deviation 9.0311
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 200 (n=18, 18, 19, 6, 6, 3)	-1.109 Percentage of predicted value	Standard Deviation 5.4668
Placebo - ONO4641 0.15 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 255 (n=47, 48, 47, 17, 16, 13)	-0.115 Percentage of predicted value	Standard Deviation 13.4126
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 152 (n=12, 12, 10, 4, 3, 8)	-2.726 Percentage of predicted value	Standard Deviation 17.6042
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 76 (n=72, 78, 74, 24, 24, 21)	0.568 Percentage of predicted value	Standard Deviation 6.453
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 255 (n=47, 48, 47, 17, 16, 13)	-1.059 Percentage of predicted value	Standard Deviation 10.2246
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Early termination (n=56, 63, 63, 19, 20, 16)	-0.892 Percentage of predicted value	Standard Deviation 5.6941
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 200 (n=18, 18, 19, 6, 6, 3)	-1.152 Percentage of predicted value	Standard Deviation 14.6922
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 52 (n=74, 84, 77, 25, 24, 21)	-0.111 Percentage of predicted value	Standard Deviation 6.2548
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 124 (n=66, 70, 68, 21, 23, 18)	-0.487 Percentage of predicted value	Standard Deviation 8.2776
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 40 (n=77,83,82,29,24,24)	1.554 Percentage of predicted value	Standard Deviation 7.9727
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 100 (n=68, 70, 72, 24, 24, 18)	-1.623 Percentage of predicted value	Standard Deviation 8.3312
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Early termination(n=16, 17, 13, 7, 3, 8)	0.459 Percentage of predicted value	Standard Deviation 16.2506
Placebo - ONO4641 0.10 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 148 (n=59, 67, 68, 20, 21, 18)	-0.715 Percentage of predicted value	Standard Deviation 6.7088
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 148 (n=59, 67, 68, 20, 21, 18)	-4.803 Percentage of predicted value	Standard Deviation 9.3143
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 255 (n=47, 48, 47, 17, 16, 13)	-0.675 Percentage of predicted value	Standard Deviation 11.1022
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 152 (n=12, 12, 10, 4, 3, 8)	-1.283 Percentage of predicted value	Standard Deviation 9.759
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 124 (n=66, 70, 68, 21, 23, 18)	-1.821 Percentage of predicted value	Standard Deviation 7.7421
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 100 (n=68, 70, 72, 24, 24, 18)	-2.927 Percentage of predicted value	Standard Deviation 7.867
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 200 (n=18, 18, 19, 6, 6, 3)	4.287 Percentage of predicted value	Standard Deviation 8.1537
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 76 (n=72, 78, 74, 24, 24, 21)	-0.707 Percentage of predicted value	Standard Deviation 11.3657
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 52 (n=74, 84, 77, 25, 24, 21)	-1.442 Percentage of predicted value	Standard Deviation 6.8125
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Early termination (n=56, 63, 63, 19, 20, 16)	-4.731 Percentage of predicted value	Standard Deviation 12.9422
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Week 40 (n=77,83,82,29,24,24)	-0.423 Percentage of predicted value	Standard Deviation 5.5244
Placebo - ONO4641 0.05 mg	Change From Baseline in Forced Vital Capacity (FVC)	Early termination(n=16, 17, 13, 7, 3, 8)	2.813 Percentage of predicted value	Standard Deviation 6.3216

Primary

Number of Subjects With Clinically Significant Abnormal Electrocardiogram (ECG) Measures

The 12-lead ECG was recorded after the subject was in supine position for 5 minutes. ECGs were acquired on digital cardiographs. Abnormal findings were analyzed as clinically significant or not clinically significant as per the discretion of the study investigator.

Time frame: Baseline up to Week 255

Population: Safety analysis set consisted of all the enrolled subjects.

Arm	Measure	Value (NUMBER)
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Electrocardiogram (ECG) Measures	4 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Electrocardiogram (ECG) Measures	0 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Electrocardiogram (ECG) Measures	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Electrocardiogram (ECG) Measures	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Electrocardiogram (ECG) Measures	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Electrocardiogram (ECG) Measures	2 Subjects

Primary

Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination

A whole body examination, paying particular attention to identify precancerous or cancerous lesions was done by a dermatologist and based on the clinical judgment of the dermatologist the abnormalities were categorized as clinically significant or clinically not significant. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject early terminated from the study during the additional 2 year period with delay shall be defined.

Time frame: Baseline up to end of the treatment, assessed up to Week 255

Population: Safety analysis set consisted of all the enrolled subjects.

Arm	Measure	Group	Value (NUMBER)
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Baseline	1 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 40	1 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 52	3 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 76	4 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 100	5 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 124	6 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 148	3 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Early termination	0 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 152	0 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 174	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 200	1 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Early termination 2	1 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 255	1 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 52	4 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 255	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Baseline	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Early termination	1 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 200	1 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 124	7 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 40	2 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 152	1 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Early termination 2	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 174	1 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 100	2 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 148	5 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 76	4 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 148	1 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 152	0 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Early termination	0 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 76	3 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 52	3 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Baseline	3 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 100	2 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 40	3 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 200	0 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 124	2 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Early termination 2	0 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 174	1 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 255	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Early termination	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 52	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 76	2 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Early termination 2	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 100	2 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 124	2 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 148	2 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 152	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 174	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 255	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 200	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Baseline	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 40	1 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 152	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 124	1 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 174	1 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 52	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Early termination 2	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 40	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 200	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 100	1 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Baseline	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 255	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Early termination	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 148	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 76	1 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 200	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 152	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Early termination 2	1 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 124	1 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 148	2 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 52	1 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 76	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 174	1 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 40	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Early termination	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 100	1 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Baseline	1 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination	Week 255	0 Subjects

Primary

Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination

Subjects underwent comprehensive ophthalmic examination (COE) including best corrected visual acuity (Snellen), manifest refractions, pupil examination, ocular motility, nystagmus, confrontation visual fields, Ishihara color plates, Amsler grid, and tonometry as well as a biomicroscopy slit lamp examination of the conjunctiva, cornea, anterior chamber, iris and lens; and a fundoscopic examination (with dilation) of the vitreous, optic nerve, retinal vessels, macula, and peripheral retina. Optical Coherence Tomography (OCT): Thicknesses of the macular retina and retinal nerve fiber layer at the optic nerve head in each eye was assessed by OCT using the fast macular thickness map scan and the fast retinal nerve fiber layer (RNFL) scan features, respectively. The abnormalities of the ophthalmologic examination was judged to be clinically significant or not as per the investigators discretion. The ophthalmologic examination was performed for both right eye (RE) and left eye (LE).

Time frame: Baseline up to Week 255

Population: Safety analysis set consisted of all the enrolled subjects. Here n signifies the number of subjects analyzed for the individual time point in the outcome measure.

Arm	Measure	Group	Value (NUMBER)
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT:LE:Early termination 2(n=51, 55, 62,19,21,16)	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 200 (n=18, 15, 20, 5, 5, 4)	0 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 148 (n=57, 67, 67, 20, 21, 18)	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 40 (n=76, 80, 82, 25, 23, 24)	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 148 (n=57, 67, 67, 20, 21, 18)	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 200 (n=19, 18, 19, 5, 5, 4)	0 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 255 (n=43, 42, 41, 15, 14, 13)	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 152 (n=12, 11, 11, 3, 2, 9)	1 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 124 (n=64, 68, 66, 19, 21, 18)	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 124 (n=64, 68, 66, 19, 21, 18)	3 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 100 (n=66, 71, 70, 23, 23, 18)	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 52 (n=74, 82, 74, 25, 22, 20)	1 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 255 (n=42, 42, 41, 15, 14, 13)	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 148 (n=58, 66, 67, 19, 21, 18)	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 52 (n=74, 82, 74, 25, 22, 20)	1 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 174 (n=57, 60, 63, 17, 21, 15)	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 152 (n=12, 11, 10, 3, 2, 9)	0 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 100 (n=66, 71, 70, 23, 23, 18)	3 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Early termination (n=14, 15, 15, 8, 2, 8)	0 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 76 (n=70, 77, 72, 24, 24, 21)	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 124 (n=65, 69, 67, 20, 22, 18)	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Baseline (n=80, 87, 89, 29, 26, 29)	4 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 124 (n=65, 69, 67, 20, 22, 18)	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 200 (n=19, 18, 19, 5, 5, 4)	0 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Early termination (n=15, 14, 16, 6, 2, 8)	1 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 100 (n=67, 72, 71, 24, 23, 18)	5 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 100 (n=67, 72, 71, 24, 23, 18)	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 76 (n=72, 79, 72, 24, 24, 21)	3 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 255 (n=43, 42, 44, 16, 14, 13)	1 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 225 (n=3, 2, 0, 0, 0, 0)	0 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 225 (n=2, 2, 0, 0, 0, 0)	0 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Baseline (n=80, 87, 89, 29, 26, 29)	4 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 200 (n=18, 15, 20, 5, 5, 4)	1 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 255 (n=43, 42, 44, 16, 14, 13)	1 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Early termination 2(n=50,56,62,19,21,16)	1 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 225 (n=3, 2, 0, 0, 0, 0)	0 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 174 (n=57, 61, 63, 17, 21, 15)	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 76 (n=72, 79, 72, 24, 24, 21)	1 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 52 (n=76, 83, 77, 26, 24, 21)	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 76 (n=69, 77, 72, 24, 24, 21)	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 52 (n=76, 83, 77, 26, 24, 21)	0 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Early termination 2(n=50,56,62,19,21,16)	1 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 152 (n=12, 11, 11, 3, 2, 9)	0 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 40 (n=78, 81, 82, 25, 23, 24)	5 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 225 (n=2, 2, 0, 0, 0, 0)	0 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Early termination (n=15, 14, 16, 6, 2, 8)	0 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 40 (n=76, 80, 81, 25, 23, 24)	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 40 (n=78, 81, 82, 25, 23, 24)	2 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 152 (n=12, 11, 10, 3, 2, 9)	0 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Baseline (n=80, 87, 89, 29, 26, 29)	0 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT:RE:Early termination 2(n=51, 55, 62,19,21,16)	4 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 148 (n=58, 66, 67, 19, 21, 18)	3 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 174 (n=57, 60, 63, 17, 21, 15)	3 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Baseline (n=80, 87, 89, 29, 26,29)	1 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 174 (n=57, 61, 63, 17, 21, 15)	0 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Early termination (n=14, 15, 15, 8, 2, 8)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 40 (n=78, 81, 82, 25, 23, 24)	1 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 76 (n=69, 77, 72, 24, 24, 21)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 255 (n=43, 42, 44, 16, 14, 13)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 174 (n=57, 61, 63, 17, 21, 15)	2 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 174 (n=57, 61, 63, 17, 21, 15)	2 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 225 (n=2, 2, 0, 0, 0, 0)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 200 (n=19, 18, 19, 5, 5, 4)	1 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 200 (n=19, 18, 19, 5, 5, 4)	1 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Early termination 2(n=50,56,62,19,21,16)	2 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 225 (n=3, 2, 0, 0, 0, 0)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Early termination (n=14, 15, 15, 8, 2, 8)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 225 (n=3, 2, 0, 0, 0, 0)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Early termination 2(n=50,56,62,19,21,16)	2 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 225 (n=2, 2, 0, 0, 0, 0)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT:RE:Early termination 2(n=51, 55, 62,19,21,16)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 152 (n=12, 11, 10, 3, 2, 9)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT:LE:Early termination 2(n=51, 55, 62,19,21,16)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 52 (n=74, 82, 74, 25, 22, 20)	1 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 255 (n=43, 42, 41, 15, 14, 13)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 255 (n=42, 42, 41, 15, 14, 13)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 76 (n=70, 77, 72, 24, 24, 21)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 52 (n=74, 82, 74, 25, 22, 20)	1 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 100 (n=66, 71, 70, 23, 23, 18)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 100 (n=66, 71, 70, 23, 23, 18)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 174 (n=57, 60, 63, 17, 21, 15)	1 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 124 (n=64, 68, 66, 19, 21, 18)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 124 (n=64, 68, 66, 19, 21, 18)	1 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 40 (n=76, 80, 82, 25, 23, 24)	1 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 148 (n=57, 67, 67, 20, 21, 18)	1 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 152 (n=12, 11, 10, 3, 2, 9)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 148 (n=57, 67, 67, 20, 21, 18)	1 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Early termination (n=14, 15, 15, 8, 2, 8)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Baseline (n=80, 87, 89, 29, 26,29)	4 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Baseline (n=80, 87, 89, 29, 26, 29)	4 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 174 (n=57, 60, 63, 17, 21, 15)	1 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 40 (n=76, 80, 81, 25, 23, 24)	1 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 40 (n=78, 81, 82, 25, 23, 24)	2 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 152 (n=12, 11, 11, 3, 2, 9)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 52 (n=76, 83, 77, 26, 24, 21)	2 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 52 (n=76, 83, 77, 26, 24, 21)	2 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Baseline (n=80, 87, 89, 29, 26, 29)	1 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 76 (n=72, 79, 72, 24, 24, 21)	2 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 76 (n=72, 79, 72, 24, 24, 21)	2 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 200 (n=18, 15, 20, 5, 5, 4)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 100 (n=67, 72, 71, 24, 23, 18)	2 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 100 (n=67, 72, 71, 24, 23, 18)	1 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 148 (n=58, 66, 67, 19, 21, 18)	3 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Baseline (n=80, 87, 89, 29, 26, 29)	2 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 124 (n=65, 69, 67, 20, 22, 18)	2 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 124 (n=65, 69, 67, 20, 22, 18)	2 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 148 (n=58, 66, 67, 19, 21, 18)	2 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 200 (n=18, 15, 20, 5, 5, 4)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 255 (n=43, 42, 44, 16, 14, 13)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Early termination (n=15, 14, 16, 6, 2, 8)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Early termination (n=15, 14, 16, 6, 2, 8)	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 152 (n=12, 11, 11, 3, 2, 9)	0 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 40 (n=78, 81, 82, 25, 23, 24)	2 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Early termination (n=14, 15, 15, 8, 2, 8)	1 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 255 (n=43, 42, 44, 16, 14, 13)	3 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 100 (n=67, 72, 71, 24, 23, 18)	0 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 52 (n=74, 82, 74, 25, 22, 20)	2 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 200 (n=18, 15, 20, 5, 5, 4)	0 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Baseline (n=80, 87, 89, 29, 26, 29)	4 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 200 (n=19, 18, 19, 5, 5, 4)	0 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Early termination (n=15, 14, 16, 6, 2, 8)	1 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 100 (n=67, 72, 71, 24, 23, 18)	1 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Baseline (n=80, 87, 89, 29, 26, 29)	3 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 148 (n=58, 66, 67, 19, 21, 18)	4 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 255 (n=43, 42, 44, 16, 14, 13)	3 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Early termination (n=14, 15, 15, 8, 2, 8)	1 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 52 (n=76, 83, 77, 26, 24, 21)	4 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Early termination 2(n=50,56,62,19,21,16)	3 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Baseline (n=80, 87, 89, 29, 26,29)	3 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 124 (n=65, 69, 67, 20, 22, 18)	3 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 152 (n=12, 11, 10, 3, 2, 9)	2 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Baseline (n=80, 87, 89, 29, 26, 29)	2 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 52 (n=74, 82, 74, 25, 22, 20)	2 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 225 (n=2, 2, 0, 0, 0, 0)	0 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 76 (n=70, 77, 72, 24, 24, 21)	1 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 152 (n=12, 11, 11, 3, 2, 9)	2 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Early termination (n=15, 14, 16, 6, 2, 8)	1 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 52 (n=76, 83, 77, 26, 24, 21)	3 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 148 (n=57, 67, 67, 20, 21, 18)	2 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT:RE:Early termination 2(n=51, 55, 62,19,21,16)	2 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 100 (n=66, 71, 70, 23, 23, 18)	1 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 40 (n=78, 81, 82, 25, 23, 24)	2 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 225 (n=3, 2, 0, 0, 0, 0)	0 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 255 (n=42, 42, 41, 15, 14, 13)	1 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 200 (n=18, 15, 20, 5, 5, 4)	0 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 124 (n=65, 69, 67, 20, 22, 18)	1 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 100 (n=66, 71, 70, 23, 23, 18)	1 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 76 (n=72, 79, 72, 24, 24, 21)	4 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 40 (n=76, 80, 81, 25, 23, 24)	3 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 174 (n=57, 60, 63, 17, 21, 15)	2 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 225 (n=3, 2, 0, 0, 0, 0)	0 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 76 (n=69, 77, 72, 24, 24, 21)	1 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 124 (n=64, 68, 66, 19, 21, 18)	1 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 225 (n=2, 2, 0, 0, 0, 0)	0 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 174 (n=57, 60, 63, 17, 21, 15)	3 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 40 (n=76, 80, 82, 25, 23, 24)	3 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 255 (n=43, 42, 41, 15, 14, 13)	2 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Early termination 2(n=50,56,62,19,21,16)	2 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 124 (n=64, 68, 66, 19, 21, 18)	1 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 76 (n=72, 79, 72, 24, 24, 21)	5 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 174 (n=57, 61, 63, 17, 21, 15)	2 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 200 (n=19, 18, 19, 5, 5, 4)	0 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 152 (n=12, 11, 10, 3, 2, 9)	0 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 152 (n=12, 11, 11, 3, 2, 9)	1 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 148 (n=57, 67, 67, 20, 21, 18)	2 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 174 (n=57, 61, 63, 17, 21, 15)	4 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 148 (n=58, 66, 67, 19, 21, 18)	3 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT:LE:Early termination 2(n=51, 55, 62,19,21,16)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT:LE:Early termination 2(n=51, 55, 62,19,21,16)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 148 (n=58, 66, 67, 19, 21, 18)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 148 (n=57, 67, 67, 20, 21, 18)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Early termination (n=14, 15, 15, 8, 2, 8)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 40 (n=76, 80, 81, 25, 23, 24)	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Early termination 2(n=50,56,62,19,21,16)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT:RE:Early termination 2(n=51, 55, 62,19,21,16)	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Baseline (n=80, 87, 89, 29, 26,29)	2 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 52 (n=74, 82, 74, 25, 22, 20)	2 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 174 (n=57, 61, 63, 17, 21, 15)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Baseline (n=80, 87, 89, 29, 26, 29)	2 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 148 (n=58, 66, 67, 19, 21, 18)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 225 (n=2, 2, 0, 0, 0, 0)	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 152 (n=12, 11, 11, 3, 2, 9)	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 40 (n=78, 81, 82, 25, 23, 24)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 40 (n=78, 81, 82, 25, 23, 24)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 174 (n=57, 60, 63, 17, 21, 15)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Baseline (n=80, 87, 89, 29, 26, 29)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Early termination 2(n=50,56,62,19,21,16)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 52 (n=76, 83, 77, 26, 24, 21)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 225 (n=3, 2, 0, 0, 0, 0)	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 52 (n=76, 83, 77, 26, 24, 21)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 76 (n=69, 77, 72, 24, 24, 21)	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Early termination (n=15, 14, 16, 6, 2, 8)	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 76 (n=72, 79, 72, 24, 24, 21)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 225 (n=3, 2, 0, 0, 0, 0)	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 225 (n=2, 2, 0, 0, 0, 0)	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 174 (n=57, 61, 63, 17, 21, 15)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 76 (n=72, 79, 72, 24, 24, 21)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Baseline (n=80, 87, 89, 29, 26, 29)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 200 (n=19, 18, 19, 5, 5, 4)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 100 (n=67, 72, 71, 24, 23, 18)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Early termination (n=15, 14, 16, 6, 2, 8)	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 100 (n=67, 72, 71, 24, 23, 18)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 200 (n=18, 15, 20, 5, 5, 4)	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 200 (n=18, 15, 20, 5, 5, 4)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 255 (n=43, 42, 44, 16, 14, 13)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 124 (n=65, 69, 67, 20, 22, 18)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 152 (n=12, 11, 10, 3, 2, 9)	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 76 (n=70, 77, 72, 24, 24, 21)	2 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Early termination (n=14, 15, 15, 8, 2, 8)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 200 (n=19, 18, 19, 5, 5, 4)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 52 (n=74, 82, 74, 25, 22, 20)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 152 (n=12, 11, 11, 3, 2, 9)	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 100 (n=66, 71, 70, 23, 23, 18)	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 255 (n=42, 42, 41, 15, 14, 13)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 152 (n=12, 11, 10, 3, 2, 9)	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 100 (n=66, 71, 70, 23, 23, 18)	2 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 124 (n=65, 69, 67, 20, 22, 18)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 40 (n=76, 80, 82, 25, 23, 24)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 255 (n=43, 42, 41, 15, 14, 13)	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 124 (n=64, 68, 66, 19, 21, 18)	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 255 (n=43, 42, 44, 16, 14, 13)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 124 (n=64, 68, 66, 19, 21, 18)	1 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 174 (n=57, 60, 63, 17, 21, 15)	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 148 (n=57, 67, 67, 20, 21, 18)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 225 (n=2, 2, 0, 0, 0, 0)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 152 (n=12, 11, 10, 3, 2, 9)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 152 (n=12, 11, 10, 3, 2, 9)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 174 (n=57, 60, 63, 17, 21, 15)	1 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 174 (n=57, 60, 63, 17, 21, 15)	1 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 200 (n=18, 15, 20, 5, 5, 4)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 200 (n=18, 15, 20, 5, 5, 4)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Early termination (n=14, 15, 15, 8, 2, 8)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 225 (n=2, 2, 0, 0, 0, 0)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT:RE:Early termination 2(n=51, 55, 62,19,21,16)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT:LE:Early termination 2(n=51, 55, 62,19,21,16)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 255 (n=43, 42, 41, 15, 14, 13)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 255 (n=42, 42, 41, 15, 14, 13)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 76 (n=70, 77, 72, 24, 24, 21)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 100 (n=66, 71, 70, 23, 23, 18)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 100 (n=66, 71, 70, 23, 23, 18)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 124 (n=64, 68, 66, 19, 21, 18)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 124 (n=64, 68, 66, 19, 21, 18)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 148 (n=57, 67, 67, 20, 21, 18)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 148 (n=57, 67, 67, 20, 21, 18)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Baseline (n=80, 87, 89, 29, 26,29)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Baseline (n=80, 87, 89, 29, 26, 29)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 40 (n=78, 81, 82, 25, 23, 24)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 40 (n=78, 81, 82, 25, 23, 24)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 52 (n=76, 83, 77, 26, 24, 21)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 52 (n=76, 83, 77, 26, 24, 21)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 76 (n=72, 79, 72, 24, 24, 21)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 76 (n=72, 79, 72, 24, 24, 21)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 100 (n=67, 72, 71, 24, 23, 18)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 100 (n=67, 72, 71, 24, 23, 18)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 124 (n=65, 69, 67, 20, 22, 18)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 124 (n=65, 69, 67, 20, 22, 18)	1 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 148 (n=58, 66, 67, 19, 21, 18)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 148 (n=58, 66, 67, 19, 21, 18)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Early termination (n=15, 14, 16, 6, 2, 8)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Early termination (n=15, 14, 16, 6, 2, 8)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 152 (n=12, 11, 11, 3, 2, 9)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 152 (n=12, 11, 11, 3, 2, 9)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 174 (n=57, 61, 63, 17, 21, 15)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 174 (n=57, 61, 63, 17, 21, 15)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 200 (n=19, 18, 19, 5, 5, 4)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 200 (n=19, 18, 19, 5, 5, 4)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 225 (n=3, 2, 0, 0, 0, 0)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 225 (n=3, 2, 0, 0, 0, 0)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Early termination 2(n=50,56,62,19,21,16)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Early termination 2(n=50,56,62,19,21,16)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 255 (n=43, 42, 44, 16, 14, 13)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 255 (n=43, 42, 44, 16, 14, 13)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Baseline (n=80, 87, 89, 29, 26, 29)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Baseline (n=80, 87, 89, 29, 26, 29)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 40 (n=76, 80, 81, 25, 23, 24)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 40 (n=76, 80, 82, 25, 23, 24)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 52 (n=74, 82, 74, 25, 22, 20)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 52 (n=74, 82, 74, 25, 22, 20)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 76 (n=69, 77, 72, 24, 24, 21)	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Early termination (n=14, 15, 15, 8, 2, 8)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Early termination (n=15, 14, 16, 6, 2, 8)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 200 (n=18, 15, 20, 5, 5, 4)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 255 (n=43, 42, 44, 16, 14, 13)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Early termination (n=15, 14, 16, 6, 2, 8)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 148 (n=58, 66, 67, 19, 21, 18)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 148 (n=58, 66, 67, 19, 21, 18)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 124 (n=65, 69, 67, 20, 22, 18)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 200 (n=18, 15, 20, 5, 5, 4)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 255 (n=43, 42, 44, 16, 14, 13)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 124 (n=65, 69, 67, 20, 22, 18)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 100 (n=67, 72, 71, 24, 23, 18)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 100 (n=67, 72, 71, 24, 23, 18)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 76 (n=72, 79, 72, 24, 24, 21)	1 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 174 (n=57, 60, 63, 17, 21, 15)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Baseline (n=80, 87, 89, 29, 26, 29)	1 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 76 (n=72, 79, 72, 24, 24, 21)	1 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 52 (n=76, 83, 77, 26, 24, 21)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 52 (n=76, 83, 77, 26, 24, 21)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 40 (n=78, 81, 82, 25, 23, 24)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 152 (n=12, 11, 10, 3, 2, 9)	1 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Baseline (n=80, 87, 89, 29, 26, 29)	1 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 40 (n=78, 81, 82, 25, 23, 24)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Baseline (n=80, 87, 89, 29, 26, 29)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Baseline (n=80, 87, 89, 29, 26,29)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 148 (n=57, 67, 67, 20, 21, 18)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 174 (n=57, 60, 63, 17, 21, 15)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 40 (n=76, 80, 81, 25, 23, 24)	1 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 148 (n=57, 67, 67, 20, 21, 18)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 124 (n=64, 68, 66, 19, 21, 18)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 124 (n=64, 68, 66, 19, 21, 18)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 100 (n=66, 71, 70, 23, 23, 18)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Early termination (n=14, 15, 15, 8, 2, 8)	1 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 40 (n=76, 80, 82, 25, 23, 24)	1 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 100 (n=66, 71, 70, 23, 23, 18)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 76 (n=70, 77, 72, 24, 24, 21)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 76 (n=69, 77, 72, 24, 24, 21)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 255 (n=42, 42, 41, 15, 14, 13)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Early termination (n=14, 15, 15, 8, 2, 8)	1 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 52 (n=74, 82, 74, 25, 22, 20)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 255 (n=43, 42, 41, 15, 14, 13)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT:LE:Early termination 2(n=51, 55, 62,19,21,16)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT:RE:Early termination 2(n=51, 55, 62,19,21,16)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 225 (n=2, 2, 0, 0, 0, 0)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 152 (n=12, 11, 10, 3, 2, 9)	1 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 225 (n=3, 2, 0, 0, 0, 0)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: LE: Week 52 (n=74, 82, 74, 25, 22, 20)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Early termination 2(n=50,56,62,19,21,16)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 225 (n=3, 2, 0, 0, 0, 0)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 200 (n=19, 18, 19, 5, 5, 4)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 200 (n=19, 18, 19, 5, 5, 4)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 174 (n=57, 61, 63, 17, 21, 15)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	OCT: RE: Week 225 (n=2, 2, 0, 0, 0, 0)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Early termination 2(n=50,56,62,19,21,16)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 174 (n=57, 61, 63, 17, 21, 15)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: LE: Week 152 (n=12, 11, 11, 3, 2, 9)	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination	COE: RE: Week 152 (n=12, 11, 11, 3, 2, 9)	0 Subjects

Primary

Number of Subjects With Clinically Significant Abnormal Vital Signs

Vital signs included oral temperature, pulse, respiration rate and blood pressure (BP) (taken after 5 minutes in the sitting position). The abnormalities in vital signs were decided as clinically significant or not based on the clinical judgment of the investigator.

Time frame: Baseline up to Week 255

Population: Safety analysis set consisted of all the enrolled subjects.

Arm	Measure	Value (NUMBER)
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Clinically Significant Abnormal Vital Signs	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Clinically Significant Abnormal Vital Signs	0 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Clinically Significant Abnormal Vital Signs	0 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Clinically Significant Abnormal Vital Signs	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Clinically Significant Abnormal Vital Signs	0 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Clinically Significant Abnormal Vital Signs	0 Subjects

Primary

Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation

An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A Serious Adverse Event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were defined as the AEs that occur between first dose of study drug administration and 35 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pretreatment state.

Time frame: From the first dose of study drug administration up to 35 days after the last dose of study drug administration, assessed up to 5 years

Population: Safety analysis set consisted of all the enrolled subjects.

Arm	Measure	Group	Value (NUMBER)
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	TEAEs	75 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	Serious TEAEs	16 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	TEAEs leading to death	1 Subjects
ONO-4641 0.15 mg - 0.15 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	TEAEs leading to discontinuation	6 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	TEAEs leading to death	0 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	Serious TEAEs	12 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	TEAEs	85 Subjects
ONO-4641 0.10 mg - 0.10 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	TEAEs leading to discontinuation	6 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	TEAEs leading to discontinuation	7 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	TEAEs leading to death	0 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	Serious TEAEs	21 Subjects
ONO-4641 0.05 mg - 0.05 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	TEAEs	82 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	TEAEs	27 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	TEAEs leading to discontinuation	3 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	Serious TEAEs	5 Subjects
Placebo - ONO4641 0.15 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	TEAEs leading to death	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	TEAEs leading to death	0 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	TEAEs leading to discontinuation	2 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	Serious TEAEs	9 Subjects
Placebo - ONO4641 0.10 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	TEAEs	22 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	Serious TEAEs	11 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	TEAEs leading to death	1 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	TEAEs leading to discontinuation	6 Subjects
Placebo - ONO4641 0.05 mg	Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation	TEAEs	29 Subjects

Secondary

Change From Baseline in Lesion Volume at the End of the Treatment (EoT)

Brain lesion volume was obtained by magnetic resonance imaging (MRI). Extension study baseline was defined as the measurement most immediately prior to or on the day of the first dose day of extension study. End of treatment (EOT) was defined as the last visit during the treatment period. Change from extension baseline to EOT = last treatment period value in extension study - extension baseline value.

Time frame: Baseline, End of treatment (5 years)

Population: FAS included all subjects who provided any post baseline efficacy data.One randomized error subject was summarized in the sequence 0.15-0.15 as he received 0.15 in core study period and in the sequence Placebo-0.10 mg as he received 0.10 in the extension study period.

Arm	Measure	Value (MEAN)	Dispersion
ONO-4641 0.15 mg - 0.15 mg	Change From Baseline in Lesion Volume at the End of the Treatment (EoT)	-0.0264 Cubic centimeter (cc)	Standard Deviation 0.15483
ONO-4641 0.10 mg - 0.10 mg	Change From Baseline in Lesion Volume at the End of the Treatment (EoT)	0.0294 Cubic centimeter (cc)	Standard Deviation 0.11275
ONO-4641 0.05 mg - 0.05 mg	Change From Baseline in Lesion Volume at the End of the Treatment (EoT)	0.0197 Cubic centimeter (cc)	Standard Deviation 0.19925
Placebo - ONO4641 0.15 mg	Change From Baseline in Lesion Volume at the End of the Treatment (EoT)	-0.4548 Cubic centimeter (cc)	Standard Deviation 0.96555
Placebo - ONO4641 0.10 mg	Change From Baseline in Lesion Volume at the End of the Treatment (EoT)	-0.4465 Cubic centimeter (cc)	Standard Deviation 1.22881
Placebo - ONO4641 0.05 mg	Change From Baseline in Lesion Volume at the End of the Treatment (EoT)	-0.1105 Cubic centimeter (cc)	Standard Deviation 0.36973

Secondary

Number of Gadolinium (Gd)-Enhanced Lesions

Gd-enhanced lesions were obtained by magnetic resonance imaging (MRI) at each scheduled assessment visit over the study period. Extension study baseline is defined as the measurement most immediately prior to or on the day of the first dose day of extension study. End of treatment (EoT) lesion count is the average number of lesion counts per scan, calculated by dividing the sum of all lesion counts by number of scans during the extension treatment period. Early termination visit was recorded when the subject was early terminated from the study during the first 2.5 year period, while early termination 2 visit was recorded when the subject early terminated from the study during the additional 2 year period with delay. Extension study baseline is defined as the measurement most immediately prior to or on the day of the first dose day of extension study.Full Analysis Set (FAS) included all subjects who provided any post baseline efficacy data.

Time frame: Baseline, Week 40, 52, 100, 148, early termination, Week 152, 200, early termination 2, Week 255 and end of treatment (5 years)

Population: FAS. n signifies the number of subjects analyzed for individual time point in the outcome measure.One randomized error subject was summarized in the sequence 0.15-0.15 as he received 0.15 in core study period and in the sequence Placebo-0.10 mg as he received 0.10 in the extension study period.

Arm	Measure	Group	Value (MEAN)	Dispersion
ONO-4641 0.15 mg - 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Early termination (n=16, 14, 13, 6, 3, 6)	0.8 Lesions	Standard Deviation 2.76
ONO-4641 0.15 mg - 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 200 (n=20, 18, 21, 28, 27, 28)	0.0 Lesions	Standard Deviation 0
ONO-4641 0.15 mg - 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 148 (n=61, 67, 68, 18, 22, 18)	0.0 Lesions	Standard Deviation 0.22
ONO-4641 0.15 mg - 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	End of treatment (n=80, 84, 85, 28, 24, 25)	0.1 Lesions	Standard Deviation 0.39
ONO-4641 0.15 mg - 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 40 (n=78, 84, 82, 28, 24, 25)	0.2 Lesions	Standard Deviation 0.67
ONO-4641 0.15 mg - 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Baseline	0.2 Lesions	Standard Deviation 0.57
ONO-4641 0.15 mg - 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 255 (n=46, 48, 48, 16, 17, 13)	1.1 Lesions	Standard Deviation 5.9
ONO-4641 0.15 mg - 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Early Termination 2 (n=58, 61, 60, 17, 21, 16)	0.1 Lesions	Standard Deviation 0.34
ONO-4641 0.15 mg - 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 52 (n=77, 84, 77, 25, 24, 21)	0.2 Lesions	Standard Deviation 0.86
ONO-4641 0.15 mg - 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 152 (n=11, 10, 8, 4, 3, 6)	0.2 Lesions	Standard Deviation 0.6
ONO-4641 0.15 mg - 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 100 (n=71, 73, 72, 22, 24, 18)	0.1 Lesions	Standard Deviation 0.49
ONO-4641 0.10 mg - 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Early termination (n=16, 14, 13, 6, 3, 6)	0.1 Lesions	Standard Deviation 0.36
ONO-4641 0.10 mg - 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 100 (n=71, 73, 72, 22, 24, 18)	0.2 Lesions	Standard Deviation 0.76
ONO-4641 0.10 mg - 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 52 (n=77, 84, 77, 25, 24, 21)	0.2 Lesions	Standard Deviation 1.23
ONO-4641 0.10 mg - 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 148 (n=61, 67, 68, 18, 22, 18)	0.1 Lesions	Standard Deviation 0.99
ONO-4641 0.10 mg - 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Baseline	0.0 Lesions	Standard Deviation 0.18
ONO-4641 0.10 mg - 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 255 (n=46, 48, 48, 16, 17, 13)	0.3 Lesions	Standard Deviation 1.01
ONO-4641 0.10 mg - 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 200 (n=20, 18, 21, 28, 27, 28)	0.5 Lesions	Standard Deviation 1.29
ONO-4641 0.10 mg - 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 40 (n=78, 84, 82, 28, 24, 25)	0.1 Lesions	Standard Deviation 0.62
ONO-4641 0.10 mg - 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 152 (n=11, 10, 8, 4, 3, 6)	0.6 Lesions	Standard Deviation 0.97
ONO-4641 0.10 mg - 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	End of treatment (n=80, 84, 85, 28, 24, 25)	0.2 Lesions	Standard Deviation 0.64
ONO-4641 0.10 mg - 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Early Termination 2 (n=58, 61, 60, 17, 21, 16)	0.2 Lesions	Standard Deviation 0.87
ONO-4641 0.05 mg - 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 40 (n=78, 84, 82, 28, 24, 25)	0.4 Lesions	Standard Deviation 1.32
ONO-4641 0.05 mg - 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Baseline	0.3 Lesions	Standard Deviation 0.65
ONO-4641 0.05 mg - 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 52 (n=77, 84, 77, 25, 24, 21)	0.4 Lesions	Standard Deviation 0.93
ONO-4641 0.05 mg - 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 100 (n=71, 73, 72, 22, 24, 18)	0.4 Lesions	Standard Deviation 1.37
ONO-4641 0.05 mg - 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 148 (n=61, 67, 68, 18, 22, 18)	0.6 Lesions	Standard Deviation 1.85
ONO-4641 0.05 mg - 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Early termination (n=16, 14, 13, 6, 3, 6)	1.5 Lesions	Standard Deviation 4.68
ONO-4641 0.05 mg - 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 152 (n=11, 10, 8, 4, 3, 6)	2.5 Lesions	Standard Deviation 6.3
ONO-4641 0.05 mg - 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 200 (n=20, 18, 21, 28, 27, 28)	0.2 Lesions	Standard Deviation 0.89
ONO-4641 0.05 mg - 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Early Termination 2 (n=58, 61, 60, 17, 21, 16)	0.2 Lesions	Standard Deviation 0.38
ONO-4641 0.05 mg - 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 255 (n=46, 48, 48, 16, 17, 13)	0.4 Lesions	Standard Deviation 1.38
ONO-4641 0.05 mg - 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	End of treatment (n=80, 84, 85, 28, 24, 25)	0.4 Lesions	Standard Deviation 0.93
Placebo - ONO4641 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 40 (n=78, 84, 82, 28, 24, 25)	0.2 Lesions	Standard Deviation 0.42
Placebo - ONO4641 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 200 (n=20, 18, 21, 28, 27, 28)	0.0 Lesions	Standard Deviation 0
Placebo - ONO4641 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 100 (n=71, 73, 72, 22, 24, 18)	0.2 Lesions	Standard Deviation 0.53
Placebo - ONO4641 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Early Termination 2 (n=58, 61, 60, 17, 21, 16)	0.1 Lesions	Standard Deviation 0.33
Placebo - ONO4641 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	End of treatment (n=80, 84, 85, 28, 24, 25)	0.2 Lesions	Standard Deviation 0.39
Placebo - ONO4641 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 148 (n=61, 67, 68, 18, 22, 18)	0.0 Lesions	Standard Deviation 0
Placebo - ONO4641 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 255 (n=46, 48, 48, 16, 17, 13)	1.6 Lesions	Standard Deviation 3.9
Placebo - ONO4641 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Early termination (n=16, 14, 13, 6, 3, 6)	0.2 Lesions	Standard Deviation 0.41
Placebo - ONO4641 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Baseline	2.7 Lesions	Standard Deviation 3.88
Placebo - ONO4641 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 152 (n=11, 10, 8, 4, 3, 6)	0.8 Lesions	Standard Deviation 1.5
Placebo - ONO4641 0.15 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 52 (n=77, 84, 77, 25, 24, 21)	0.2 Lesions	Standard Deviation 0.65
Placebo - ONO4641 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 100 (n=71, 73, 72, 22, 24, 18)	0.1 Lesions	Standard Deviation 0.34
Placebo - ONO4641 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Baseline	3.6 Lesions	Standard Deviation 10.46
Placebo - ONO4641 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Early termination (n=16, 14, 13, 6, 3, 6)	0.0 Lesions	Standard Deviation 0
Placebo - ONO4641 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 52 (n=77, 84, 77, 25, 24, 21)	0.1 Lesions	Standard Deviation 0.34
Placebo - ONO4641 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 200 (n=20, 18, 21, 28, 27, 28)	0.5 Lesions	Standard Deviation 1.22
Placebo - ONO4641 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 40 (n=78, 84, 82, 28, 24, 25)	0.3 Lesions	Standard Deviation 1
Placebo - ONO4641 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Early Termination 2 (n=58, 61, 60, 17, 21, 16)	0.2 Lesions	Standard Deviation 0.51
Placebo - ONO4641 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	End of treatment (n=80, 84, 85, 28, 24, 25)	0.2 Lesions	Standard Deviation 0.53
Placebo - ONO4641 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 255 (n=46, 48, 48, 16, 17, 13)	0.2 Lesions	Standard Deviation 0.53
Placebo - ONO4641 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 152 (n=11, 10, 8, 4, 3, 6)	0.0 Lesions	Standard Deviation 0
Placebo - ONO4641 0.10 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 148 (n=61, 67, 68, 18, 22, 18)	0.2 Lesions	Standard Deviation 0.66
Placebo - ONO4641 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Baseline	1.6 Lesions	Standard Deviation 3.74
Placebo - ONO4641 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Early termination (n=16, 14, 13, 6, 3, 6)	0.5 Lesions	Standard Deviation 0.84
Placebo - ONO4641 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 52 (n=77, 84, 77, 25, 24, 21)	0.4 Lesions	Standard Deviation 0.68
Placebo - ONO4641 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 100 (n=71, 73, 72, 22, 24, 18)	0.1 Lesions	Standard Deviation 0.47
Placebo - ONO4641 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 255 (n=46, 48, 48, 16, 17, 13)	0.3 Lesions	Standard Deviation 0.85
Placebo - ONO4641 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 148 (n=61, 67, 68, 18, 22, 18)	0.1 Lesions	Standard Deviation 0.47
Placebo - ONO4641 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 40 (n=78, 84, 82, 28, 24, 25)	0.2 Lesions	Standard Deviation 0.5
Placebo - ONO4641 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 200 (n=20, 18, 21, 28, 27, 28)	0.0 Lesions	Standard Deviation 0
Placebo - ONO4641 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Week 152 (n=11, 10, 8, 4, 3, 6)	0.3 Lesions	Standard Deviation 0.82
Placebo - ONO4641 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	Early Termination 2 (n=58, 61, 60, 17, 21, 16)	0.4 Lesions	Standard Deviation 1.26
Placebo - ONO4641 0.05 mg	Number of Gadolinium (Gd)-Enhanced Lesions	End of treatment (n=80, 84, 85, 28, 24, 25)	0.3 Lesions	Standard Deviation 0.5

Secondary

Percent Brain Volume Change (PBVC) From Baseline at the End of Treatment

Brain volume was obtained by magnetic resonance imaging (MRI). Extension study baseline is defined as the measurement most immediately prior to or on the day of the first dose day of extension study. Brain volume changes very little over time. Hence, the PBVC at the end of treatment was calculated by adding up all the PBVC values from the scans performed during the extension treatment period.

Time frame: Baseline and at end of treatment (Week 255)

Population: FAS included all subjects who provided any post baseline efficacy data. One randomized error subject was summarized in the sequence 0.15-0.15 as he received 0.15 in core study period and in the sequence Placebo-0.10 mg as he received 0.10 in the extension study period.

Arm	Measure	Value (MEAN)	Dispersion
ONO-4641 0.15 mg - 0.15 mg	Percent Brain Volume Change (PBVC) From Baseline at the End of Treatment	-0.845 Percent brain volume	Standard Deviation 0.8745
ONO-4641 0.10 mg - 0.10 mg	Percent Brain Volume Change (PBVC) From Baseline at the End of Treatment	-0.713 Percent brain volume	Standard Deviation 0.8558
ONO-4641 0.05 mg - 0.05 mg	Percent Brain Volume Change (PBVC) From Baseline at the End of Treatment	-0.757 Percent brain volume	Standard Deviation 0.7554
Placebo - ONO4641 0.15 mg	Percent Brain Volume Change (PBVC) From Baseline at the End of Treatment	-0.756 Percent brain volume	Standard Deviation 0.8239
Placebo - ONO4641 0.10 mg	Percent Brain Volume Change (PBVC) From Baseline at the End of Treatment	-1.302 Percent brain volume	Standard Deviation 0.9643
Placebo - ONO4641 0.05 mg	Percent Brain Volume Change (PBVC) From Baseline at the End of Treatment	-0.972 Percent brain volume	Standard Deviation 0.8215

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Phase 2 Extension Trial in Patients With Relapsing-Remitting Multiple Sclerosis (RRMS)

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO)

Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Percent (%) Predicted Value)

Change From Baseline in Forced Vital Capacity (FVC)

Number of Subjects With Clinically Significant Abnormal Electrocardiogram (ECG) Measures

Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination

Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination

Number of Subjects With Clinically Significant Abnormal Vital Signs

Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation

Change From Baseline in Lesion Volume at the End of the Treatment (EoT)

Number of Gadolinium (Gd)-Enhanced Lesions

Percent Brain Volume Change (PBVC) From Baseline at the End of Treatment