Trial Outcomes & Findings for Phase 2 Extension Trial in Patients With Relapsing-Remitting Multiple Sclerosis (RRMS) (NCT NCT01226745)
NCT ID: NCT01226745
Last Updated: 2016-07-12
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
340 participants
Primary outcome timeframe
Baseline up to Week 255
Results posted on
2016-07-12
Participant Flow
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.
Participant milestones
| Measure |
ONO-4641 0.15 Milligram (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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
80
|
87
|
89
|
29
|
26
|
29
|
|
Overall Study
COMPLETED
|
63
|
71
|
69
|
24
|
22
|
24
|
|
Overall Study
NOT COMPLETED
|
17
|
16
|
20
|
5
|
4
|
5
|
Reasons for withdrawal
| Measure |
ONO-4641 0.15 Milligram (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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
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
Death
|
1
|
0
|
0
|
0
|
0
|
1
|
|
Overall Study
Other
|
6
|
7
|
8
|
4
|
3
|
1
|
Baseline Characteristics
Phase 2 Extension Trial in Patients With Relapsing-Remitting Multiple Sclerosis (RRMS)
Baseline characteristics by cohort
| Measure |
ONO-4641 0.15 mg - 0.15 mg
n=80 Participants
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.
|
ONO-4641 0.10 mg - 0.10 mg
n=87 Participants
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.
|
ONO-4641 0.05 mg - 0.05 mg
n=89 Participants
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.
|
Placebo - ONO4641 0.15 mg
n=29 Participants
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.
|
Placebo - ONO4641 0.10 mg
n=26 Participants
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.
|
Placebo - ONO4641 0.05 mg
n=29 Participants
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.
|
Total
n=340 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
36.3 Years
STANDARD_DEVIATION 8.47 • n=5 Participants
|
36.0 Years
STANDARD_DEVIATION 8.64 • n=7 Participants
|
38.2 Years
STANDARD_DEVIATION 8.66 • n=5 Participants
|
35.6 Years
STANDARD_DEVIATION 9.59 • n=4 Participants
|
37.0 Years
STANDARD_DEVIATION 6.96 • n=21 Participants
|
38.7 Years
STANDARD_DEVIATION 9.48 • n=8 Participants
|
36.9 Years
STANDARD_DEVIATION 8.66 • n=8 Participants
|
|
Sex: Female, Male
Female
|
53 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
66 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
17 Participants
n=21 Participants
|
24 Participants
n=8 Participants
|
252 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
5 Participants
n=8 Participants
|
88 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Week 255Population: Safety analysis set consisted of all the enrolled subjects.
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.
Outcome measures
| Measure |
ONO-4641 0.15 mg - 0.15 mg
n=80 Participants
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.
|
ONO-4641 0.10 mg - 0.10 mg
n=87 Participants
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.
|
ONO-4641 0.05 mg - 0.05 mg
n=89 Participants
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.
|
Placebo - ONO4641 0.15 mg
n=29 Participants
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.
|
Placebo - ONO4641 0.10 mg
n=26 Participants
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.
|
Placebo - ONO4641 0.05 mg
n=29 Participants
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.
|
|---|---|---|---|---|---|---|
|
Number of Subjects With Clinically Significant Abnormal Vital Signs
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
PRIMARY outcome
Timeframe: Baseline, Week 40, 52, 76, 100, 124, 148, early termination, Week 152, 200, early termination 2, Week 255Population: 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.
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.
Outcome measures
| Measure |
ONO-4641 0.15 mg - 0.15 mg
n=80 Participants
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.
|
ONO-4641 0.10 mg - 0.10 mg
n=87 Participants
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.
|
ONO-4641 0.05 mg - 0.05 mg
n=89 Participants
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.
|
Placebo - ONO4641 0.15 mg
n=29 Participants
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.
|
Placebo - ONO4641 0.10 mg
n=26 Participants
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.
|
Placebo - ONO4641 0.05 mg
n=29 Participants
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.
|
|---|---|---|---|---|---|---|
|
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
|
-0.741 Percentage of predicted value
Standard Deviation 6.2026
|
-0.062 Percentage of predicted value
Standard Deviation 5.4947
|
-1.500 Percentage of predicted value
Standard Deviation 5.0115
|
-1.555 Percentage of predicted value
Standard Deviation 7.8424
|
-1.146 Percentage of predicted value
Standard Deviation 4.7952
|
|
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
|
-1.981 Percentage of predicted value
Standard Deviation 6.8499
|
-0.484 Percentage of predicted value
Standard Deviation 6.0952
|
-3.113 Percentage of predicted value
Standard Deviation 5.4753
|
-2.851 Percentage of predicted value
Standard Deviation 6.7997
|
-0.561 Percentage of predicted value
Standard Deviation 5.5040
|
|
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 9.5950
|
-2.352 Percentage of predicted value
Standard Deviation 6.1152
|
0.650 Percentage of predicted value
Standard Deviation 7.2084
|
-1.574 Percentage of predicted value
Standard Deviation 6.3645
|
-2.300 Percentage of predicted value
Standard Deviation 9.2869
|
2.657 Percentage of predicted value
Standard Deviation 8.9280
|
|
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
|
-2.790 Percentage of predicted value
Standard Deviation 8.2129
|
-1.187 Percentage of predicted value
Standard Deviation 7.8818
|
-3.202 Percentage of predicted value
Standard Deviation 6.7073
|
-3.748 Percentage of predicted value
Standard Deviation 8.5817
|
-1.207 Percentage of predicted value
Standard Deviation 7.7400
|
|
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
|
-2.003 Percentage of predicted value
Standard Deviation 7.7998
|
0.197 Percentage of predicted value
Standard Deviation 7.9068
|
-2.178 Percentage of predicted value
Standard Deviation 9.7656
|
-1.968 Percentage of predicted value
Standard Deviation 9.2415
|
-0.874 Percentage of predicted value
Standard Deviation 8.2237
|
|
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
|
-3.429 Percentage of predicted value
Standard Deviation 8.4036
|
-1.234 Percentage of predicted value
Standard Deviation 6.5270
|
-0.459 Percentage of predicted value
Standard Deviation 9.0302
|
-3.052 Percentage of predicted value
Standard Deviation 9.4970
|
-2.599 Percentage of predicted value
Standard Deviation 10.3997
|
|
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
|
0.443 Percentage of predicted value
Standard Deviation 6.0840
|
-1.780 Percentage of predicted value
Standard Deviation 11.6068
|
-2.984 Percentage of predicted value
Standard Deviation 13.8177
|
-4.109 Percentage of predicted value
Standard Deviation 21.4354
|
2.108 Percentage of predicted value
Standard Deviation 8.1682
|
|
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
|
4.515 Percentage of predicted value
Standard Deviation 11.3809
|
-1.725 Percentage of predicted value
Standard Deviation 7.4166
|
-11.929 Percentage of predicted value
Standard Deviation 13.1156
|
-11.525 Percentage of predicted value
Standard Deviation 12.3316
|
2.688 Percentage of predicted value
Standard Deviation 5.5468
|
|
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
|
-0.354 Percentage of predicted value
Standard Deviation 12.8489
|
-2.144 Percentage of predicted value
Standard Deviation 8.3421
|
-2.299 Percentage of predicted value
Standard Deviation 8.2038
|
-4.557 Percentage of predicted value
Standard Deviation 13.3731
|
0.944 Percentage of predicted value
Standard Deviation 7.8955
|
|
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
|
-2.031 Percentage of predicted value
Standard Deviation 10.6185
|
-2.859 Percentage of predicted value
Standard Deviation 9.6661
|
-1.321 Percentage of predicted value
Standard Deviation 8.7759
|
-1.291 Percentage of predicted value
Standard Deviation 10.4528
|
-3.249 Percentage of predicted value
Standard Deviation 11.5213
|
|
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
|
-1.374 Percentage of predicted value
Standard Deviation 11.0920
|
-0.027 Percentage of predicted value
Standard Deviation 13.0574
|
-0.209 Percentage of predicted value
Standard Deviation 12.1999
|
-2.377 Percentage of predicted value
Standard Deviation 11.6511
|
-0.963 Percentage of predicted value
Standard Deviation 14.2975
|
PRIMARY outcome
Timeframe: Baseline, Week 40, 52, 76, 100, 124, 148, early termination, Week 152, 200, early termination 2, Week 255Population: 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
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.
Outcome measures
| Measure |
ONO-4641 0.15 mg - 0.15 mg
n=80 Participants
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.
|
ONO-4641 0.10 mg - 0.10 mg
n=87 Participants
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.
|
ONO-4641 0.05 mg - 0.05 mg
n=89 Participants
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.
|
Placebo - ONO4641 0.15 mg
n=29 Participants
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.
|
Placebo - ONO4641 0.10 mg
n=26 Participants
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.
|
Placebo - ONO4641 0.05 mg
n=29 Participants
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.
|
|---|---|---|---|---|---|---|
|
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
|
-1.000 Percentage of predicted value
Standard Deviation 6.4060
|
0.921 Percentage of predicted value
Standard Deviation 6.9931
|
-1.593 Percentage of predicted value
Standard Deviation 5.0520
|
1.554 Percentage of predicted value
Standard Deviation 7.9727
|
-0.423 Percentage of predicted value
Standard Deviation 5.5244
|
|
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
|
-1.175 Percentage of predicted value
Standard Deviation 6.1523
|
0.107 Percentage of predicted value
Standard Deviation 7.7364
|
-2.690 Percentage of predicted value
Standard Deviation 5.2847
|
-0.111 Percentage of predicted value
Standard Deviation 6.2548
|
-1.442 Percentage of predicted value
Standard Deviation 6.8125
|
|
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
|
-1.906 Percentage of predicted value
Standard Deviation 6.0432
|
1.828 Percentage of predicted value
Standard Deviation 10.0612
|
-2.487 Percentage of predicted value
Standard Deviation 6.5830
|
0.568 Percentage of predicted value
Standard Deviation 6.4530
|
-0.707 Percentage of predicted value
Standard Deviation 11.3657
|
|
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
|
-2.433 Percentage of predicted value
Standard Deviation 6.6780
|
0.118 Percentage of predicted value
Standard Deviation 7.8025
|
-2.683 Percentage of predicted value
Standard Deviation 4.9870
|
-1.623 Percentage of predicted value
Standard Deviation 8.3312
|
-2.927 Percentage of predicted value
Standard Deviation 7.8670
|
|
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
|
-2.246 Percentage of predicted value
Standard Deviation 6.5967
|
0.890 Percentage of predicted value
Standard Deviation 7.8545
|
-2.582 Percentage of predicted value
Standard Deviation 8.4640
|
-0.487 Percentage of predicted value
Standard Deviation 8.2776
|
-1.821 Percentage of predicted value
Standard Deviation 7.7421
|
|
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
|
-3.078 Percentage of predicted value
Standard Deviation 6.6149
|
0.124 Percentage of predicted value
Standard Deviation 7.7589
|
-2.010 Percentage of predicted value
Standard Deviation 7.8162
|
-0.715 Percentage of predicted value
Standard Deviation 6.7088
|
-4.803 Percentage of predicted value
Standard Deviation 9.3143
|
|
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
|
-0.632 Percentage of predicted value
Standard Deviation 5.1482
|
979.704 Percentage of predicted value
Standard Deviation 3533.9625
|
0.278 Percentage of predicted value
Standard Deviation 9.2002
|
0.459 Percentage of predicted value
Standard Deviation 16.2506
|
2.813 Percentage of predicted value
Standard Deviation 6.3216
|
|
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
|
-0.074 Percentage of predicted value
Standard Deviation 6.8982
|
-2.829 Percentage of predicted value
Standard Deviation 7.0313
|
-3.748 Percentage of predicted value
Standard Deviation 9.0311
|
-2.726 Percentage of predicted value
Standard Deviation 17.6042
|
-1.283 Percentage of predicted value
Standard Deviation 9.7590
|
|
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
|
-3.057 Percentage of predicted value
Standard Deviation 12.0551
|
-1.590 Percentage of predicted value
Standard Deviation 8.9426
|
-1.109 Percentage of predicted value
Standard Deviation 5.4668
|
-1.152 Percentage of predicted value
Standard Deviation 14.6922
|
4.287 Percentage of predicted value
Standard Deviation 8.1537
|
|
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
|
-1.952 Percentage of predicted value
Standard Deviation 9.6157
|
-0.903 Percentage of predicted value
Standard Deviation 10.0341
|
-1.593 Percentage of predicted value
Standard Deviation 8.6842
|
-0.892 Percentage of predicted value
Standard Deviation 5.6941
|
-4.731 Percentage of predicted value
Standard Deviation 12.9422
|
|
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
|
-1.686 Percentage of predicted value
Standard Deviation 10.4560
|
1.386 Percentage of predicted value
Standard Deviation 13.9970
|
-0.115 Percentage of predicted value
Standard Deviation 13.4126
|
-1.059 Percentage of predicted value
Standard Deviation 10.2246
|
-0.675 Percentage of predicted value
Standard Deviation 11.1022
|
PRIMARY outcome
Timeframe: Baseline, Week 40, 52, early termination, Week 152, 200, 255Population: 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.
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.
Outcome measures
| Measure |
ONO-4641 0.15 mg - 0.15 mg
n=80 Participants
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.
|
ONO-4641 0.10 mg - 0.10 mg
n=87 Participants
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.
|
ONO-4641 0.05 mg - 0.05 mg
n=89 Participants
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.
|
Placebo - ONO4641 0.15 mg
n=29 Participants
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.
|
Placebo - ONO4641 0.10 mg
n=26 Participants
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.
|
Placebo - ONO4641 0.05 mg
n=29 Participants
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.
|
|---|---|---|---|---|---|---|
|
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
|
21.0 Percentage of predicted value
Standard Deviation 29.40
|
27.8 Percentage of predicted value
Standard Deviation 37.38
|
5.8 Percentage of predicted value
Standard Deviation 32.79
|
37.5 Percentage of predicted value
Standard Deviation 40.78
|
16.3 Percentage of predicted value
Standard Deviation 19.52
|
|
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
|
-1.0 Percentage of predicted value
Standard Deviation 10.98
|
-2.4 Percentage of predicted value
Standard Deviation 17.36
|
-5.3 Percentage of predicted value
Standard Deviation 16.02
|
-2.7 Percentage of predicted value
Standard Deviation 10.61
|
3.3 Percentage of predicted value
Standard Deviation 6.40
|
|
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
|
-2.7 Percentage of predicted value
Standard Deviation 10.74
|
0.8 Percentage of predicted value
Standard Deviation 20.01
|
-5.3 Percentage of predicted value
Standard Deviation 11.56
|
-4.8 Percentage of predicted value
Standard Deviation 8.04
|
5.2 Percentage of predicted value
Standard Deviation 6.34
|
|
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
|
-9.0 Percentage of predicted value
Standard Deviation NA
Standard deviation is not evaluable as it is assessed only for 1 subject.
|
-43.0 Percentage of predicted value
Standard Deviation 46.67
|
-16.3 Percentage of predicted value
Standard Deviation 12.58
|
NA Percentage of predicted value
Standard Deviation NA
Zero subjects were assessed for this measure. Hence, no data available.
|
NA Percentage of predicted value
Standard Deviation NA
Zero subjects were assessed for this measure. Hence, no data available.
|
|
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 1.00
|
11.0 Percentage of predicted value
Standard Deviation NA
Standard deviation is not evaluable as it is assessed only for 1 subject.
|
9.5 Percentage of predicted value
Standard Deviation 3.54
|
-14.0 Percentage of predicted value
Standard Deviation NA
Standard deviation is not evaluable as it is assessed only for 1 subject.
|
NA Percentage of predicted value
Standard Deviation NA
Zero subjects were assessed for this measure. Hence, no data available.
|
NA Percentage of predicted value
Standard Deviation NA
Zero subjects were assessed for this measure. Hence, no data available.
|
|
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
|
2.0 Percentage of predicted value
Standard Deviation 12.85
|
35.8 Percentage of predicted value
Standard Deviation 34.87
|
9.5 Percentage of predicted value
Standard Deviation 28.99
|
25.0 Percentage of predicted value
Standard Deviation 12.00
|
5.0 Percentage of predicted value
Standard Deviation 9.90
|
PRIMARY outcome
Timeframe: Baseline up to Week 255Population: Safety analysis set consisted of all the enrolled subjects.
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.
Outcome measures
| Measure |
ONO-4641 0.15 mg - 0.15 mg
n=80 Participants
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.
|
ONO-4641 0.10 mg - 0.10 mg
n=87 Participants
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.
|
ONO-4641 0.05 mg - 0.05 mg
n=89 Participants
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.
|
Placebo - ONO4641 0.15 mg
n=29 Participants
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.
|
Placebo - ONO4641 0.10 mg
n=26 Participants
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.
|
Placebo - ONO4641 0.05 mg
n=29 Participants
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.
|
|---|---|---|---|---|---|---|
|
Number of Subjects With Clinically Significant Abnormal Electrocardiogram (ECG) Measures
|
4 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
2 Subjects
|
PRIMARY outcome
Timeframe: Baseline up to Week 255Population: 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.
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).
Outcome measures
| Measure |
ONO-4641 0.15 mg - 0.15 mg
n=80 Participants
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.
|
ONO-4641 0.10 mg - 0.10 mg
n=87 Participants
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.
|
ONO-4641 0.05 mg - 0.05 mg
n=89 Participants
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.
|
Placebo - ONO4641 0.15 mg
n=29 Participants
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.
|
Placebo - ONO4641 0.10 mg
n=26 Participants
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.
|
Placebo - ONO4641 0.05 mg
n=29 Participants
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.
|
|---|---|---|---|---|---|---|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: LE: Week 225 (n=2, 2, 0, 0, 0, 0)
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: RE: Baseline (n=80, 87, 89, 29, 26,29)
|
1 Subjects
|
4 Subjects
|
3 Subjects
|
2 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: LE: Baseline (n=80, 87, 89, 29, 26, 29)
|
0 Subjects
|
4 Subjects
|
3 Subjects
|
2 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: RE: Week 40 (n=78, 81, 82, 25, 23, 24)
|
2 Subjects
|
2 Subjects
|
2 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: LE: Week 124 (n=65, 69, 67, 20, 22, 18)
|
2 Subjects
|
2 Subjects
|
1 Subjects
|
1 Subjects
|
1 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: LE: Week 40 (n=78, 81, 82, 25, 23, 24)
|
5 Subjects
|
1 Subjects
|
2 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: RE: Week 52 (n=76, 83, 77, 26, 24, 21)
|
0 Subjects
|
2 Subjects
|
4 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: LE: Week 52 (n=76, 83, 77, 26, 24, 21)
|
2 Subjects
|
2 Subjects
|
3 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: RE: Week 76 (n=72, 79, 72, 24, 24, 21)
|
1 Subjects
|
2 Subjects
|
4 Subjects
|
1 Subjects
|
0 Subjects
|
1 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: LE: Week 76 (n=72, 79, 72, 24, 24, 21)
|
3 Subjects
|
2 Subjects
|
5 Subjects
|
1 Subjects
|
0 Subjects
|
1 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: RE: Week 100 (n=67, 72, 71, 24, 23, 18)
|
2 Subjects
|
2 Subjects
|
0 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: LE: Week 100 (n=67, 72, 71, 24, 23, 18)
|
5 Subjects
|
1 Subjects
|
1 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: RE: Week 124 (n=65, 69, 67, 20, 22, 18)
|
2 Subjects
|
2 Subjects
|
3 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: RE: Week 148 (n=58, 66, 67, 19, 21, 18)
|
2 Subjects
|
2 Subjects
|
3 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: LE: Week 148 (n=58, 66, 67, 19, 21, 18)
|
3 Subjects
|
3 Subjects
|
4 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: RE: Early termination (n=15, 14, 16, 6, 2, 8)
|
0 Subjects
|
0 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: LE: Early termination (n=15, 14, 16, 6, 2, 8)
|
1 Subjects
|
0 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: RE: Week 152 (n=12, 11, 11, 3, 2, 9)
|
0 Subjects
|
0 Subjects
|
2 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: RE: Week 174 (n=57, 61, 63, 17, 21, 15)
|
0 Subjects
|
2 Subjects
|
4 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: LE: Week 152 (n=12, 11, 11, 3, 2, 9)
|
1 Subjects
|
0 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: LE: Week 174 (n=57, 61, 63, 17, 21, 15)
|
2 Subjects
|
2 Subjects
|
2 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: RE: Week 200 (n=19, 18, 19, 5, 5, 4)
|
0 Subjects
|
1 Subjects
|
0 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: LE: Week 200 (n=19, 18, 19, 5, 5, 4)
|
0 Subjects
|
1 Subjects
|
0 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: RE: Week 225 (n=3, 2, 0, 0, 0, 0)
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: LE: Week 225 (n=3, 2, 0, 0, 0, 0)
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: RE: Early termination 2(n=50,56,62,19,21,16)
|
1 Subjects
|
2 Subjects
|
2 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: LE: Early termination 2(n=50,56,62,19,21,16)
|
1 Subjects
|
2 Subjects
|
3 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: RE: Week 255 (n=43, 42, 44, 16, 14, 13)
|
1 Subjects
|
0 Subjects
|
3 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
COE: LE: Week 255 (n=43, 42, 44, 16, 14, 13)
|
1 Subjects
|
0 Subjects
|
3 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: RE: Baseline (n=80, 87, 89, 29, 26, 29)
|
4 Subjects
|
2 Subjects
|
4 Subjects
|
1 Subjects
|
0 Subjects
|
1 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: LE: Baseline (n=80, 87, 89, 29, 26, 29)
|
4 Subjects
|
1 Subjects
|
2 Subjects
|
1 Subjects
|
0 Subjects
|
1 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: RE: Week 40 (n=76, 80, 81, 25, 23, 24)
|
2 Subjects
|
1 Subjects
|
3 Subjects
|
0 Subjects
|
0 Subjects
|
1 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: LE: Week 40 (n=76, 80, 82, 25, 23, 24)
|
2 Subjects
|
1 Subjects
|
3 Subjects
|
1 Subjects
|
0 Subjects
|
1 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: RE: Week 52 (n=74, 82, 74, 25, 22, 20)
|
1 Subjects
|
1 Subjects
|
2 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: LE: Week 52 (n=74, 82, 74, 25, 22, 20)
|
1 Subjects
|
1 Subjects
|
2 Subjects
|
2 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: RE: Week 76 (n=69, 77, 72, 24, 24, 21)
|
2 Subjects
|
0 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: LE: Week 76 (n=70, 77, 72, 24, 24, 21)
|
2 Subjects
|
0 Subjects
|
1 Subjects
|
2 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: RE: Week 100 (n=66, 71, 70, 23, 23, 18)
|
3 Subjects
|
0 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: LE: Week 100 (n=66, 71, 70, 23, 23, 18)
|
2 Subjects
|
0 Subjects
|
1 Subjects
|
2 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: RE: Week 124 (n=64, 68, 66, 19, 21, 18)
|
3 Subjects
|
0 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: LE: Week 124 (n=64, 68, 66, 19, 21, 18)
|
2 Subjects
|
1 Subjects
|
1 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: RE: Week 148 (n=57, 67, 67, 20, 21, 18)
|
2 Subjects
|
1 Subjects
|
2 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: LE: Week 148 (n=57, 67, 67, 20, 21, 18)
|
2 Subjects
|
1 Subjects
|
2 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: RE: Early termination (n=14, 15, 15, 8, 2, 8)
|
0 Subjects
|
0 Subjects
|
1 Subjects
|
1 Subjects
|
0 Subjects
|
1 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: LE: Early termination (n=14, 15, 15, 8, 2, 8)
|
0 Subjects
|
0 Subjects
|
1 Subjects
|
1 Subjects
|
0 Subjects
|
1 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: RE: Week 152 (n=12, 11, 10, 3, 2, 9)
|
0 Subjects
|
0 Subjects
|
2 Subjects
|
0 Subjects
|
0 Subjects
|
1 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: LE: Week 152 (n=12, 11, 10, 3, 2, 9)
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
1 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: RE: Week 174 (n=57, 60, 63, 17, 21, 15)
|
2 Subjects
|
1 Subjects
|
3 Subjects
|
0 Subjects
|
1 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: LE: Week 174 (n=57, 60, 63, 17, 21, 15)
|
3 Subjects
|
1 Subjects
|
2 Subjects
|
1 Subjects
|
1 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: RE: Week 200 (n=18, 15, 20, 5, 5, 4)
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: LE: Week 200 (n=18, 15, 20, 5, 5, 4)
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: RE: Week 225 (n=2, 2, 0, 0, 0, 0)
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT:RE:Early termination 2(n=51, 55, 62,19,21,16)
|
4 Subjects
|
0 Subjects
|
2 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT:LE:Early termination 2(n=51, 55, 62,19,21,16)
|
2 Subjects
|
0 Subjects
|
1 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: RE: Week 255 (n=43, 42, 41, 15, 14, 13)
|
2 Subjects
|
0 Subjects
|
2 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormal Ophthalmologic Examination
OCT: LE: Week 255 (n=42, 42, 41, 15, 14, 13)
|
2 Subjects
|
0 Subjects
|
1 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
PRIMARY outcome
Timeframe: Baseline up to end of the treatment, assessed up to Week 255Population: Safety analysis set consisted of all the enrolled subjects.
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.
Outcome measures
| Measure |
ONO-4641 0.15 mg - 0.15 mg
n=80 Participants
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.
|
ONO-4641 0.10 mg - 0.10 mg
n=87 Participants
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.
|
ONO-4641 0.05 mg - 0.05 mg
n=89 Participants
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.
|
Placebo - ONO4641 0.15 mg
n=29 Participants
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.
|
Placebo - ONO4641 0.10 mg
n=26 Participants
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.
|
Placebo - ONO4641 0.05 mg
n=29 Participants
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.
|
|---|---|---|---|---|---|---|
|
Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination
Baseline
|
1 Subjects
|
0 Subjects
|
3 Subjects
|
1 Subjects
|
0 Subjects
|
1 Subjects
|
|
Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination
Week 40
|
1 Subjects
|
2 Subjects
|
3 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination
Week 52
|
3 Subjects
|
4 Subjects
|
3 Subjects
|
0 Subjects
|
0 Subjects
|
1 Subjects
|
|
Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination
Week 76
|
4 Subjects
|
4 Subjects
|
3 Subjects
|
2 Subjects
|
1 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination
Week 100
|
5 Subjects
|
2 Subjects
|
2 Subjects
|
2 Subjects
|
1 Subjects
|
1 Subjects
|
|
Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination
Week 124
|
6 Subjects
|
7 Subjects
|
2 Subjects
|
2 Subjects
|
1 Subjects
|
1 Subjects
|
|
Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination
Week 148
|
3 Subjects
|
5 Subjects
|
1 Subjects
|
2 Subjects
|
0 Subjects
|
2 Subjects
|
|
Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination
Early termination
|
0 Subjects
|
1 Subjects
|
0 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination
Week 152
|
0 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination
Week 174
|
2 Subjects
|
1 Subjects
|
1 Subjects
|
0 Subjects
|
1 Subjects
|
1 Subjects
|
|
Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination
Week 200
|
1 Subjects
|
1 Subjects
|
0 Subjects
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
|
Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination
Early termination 2
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
1 Subjects
|
0 Subjects
|
1 Subjects
|
|
Number of Subjects With Clinically Significant Abnormalities in Dermatological Examination
Week 255
|
1 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
PRIMARY outcome
Timeframe: From the first dose of study drug administration up to 35 days after the last dose of study drug administration, assessed up to 5 yearsPopulation: Safety analysis set consisted of all the enrolled subjects.
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.
Outcome measures
| Measure |
ONO-4641 0.15 mg - 0.15 mg
n=80 Participants
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.
|
ONO-4641 0.10 mg - 0.10 mg
n=87 Participants
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.
|
ONO-4641 0.05 mg - 0.05 mg
n=89 Participants
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.
|
Placebo - ONO4641 0.15 mg
n=29 Participants
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.
|
Placebo - ONO4641 0.10 mg
n=26 Participants
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.
|
Placebo - ONO4641 0.05 mg
n=29 Participants
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.
|
|---|---|---|---|---|---|---|
|
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation
TEAEs
|
75 Subjects
|
85 Subjects
|
82 Subjects
|
27 Subjects
|
22 Subjects
|
29 Subjects
|
|
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation
Serious TEAEs
|
16 Subjects
|
12 Subjects
|
21 Subjects
|
5 Subjects
|
9 Subjects
|
11 Subjects
|
|
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
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
0 Subjects
|
1 Subjects
|
|
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
|
6 Subjects
|
7 Subjects
|
3 Subjects
|
2 Subjects
|
6 Subjects
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
ONO-4641 0.15 mg - 0.15 mg
n=81 Participants
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.
|
ONO-4641 0.10 mg - 0.10 mg
n=87 Participants
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.
|
ONO-4641 0.05 mg - 0.05 mg
n=89 Participants
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.
|
Placebo - ONO4641 0.15 mg
n=28 Participants
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.
|
Placebo - ONO4641 0.10 mg
n=27 Participants
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.
|
Placebo - ONO4641 0.05 mg
n=28 Participants
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.
|
|---|---|---|---|---|---|---|
|
Number of Gadolinium (Gd)-Enhanced Lesions
Baseline
|
0.2 Lesions
Standard Deviation 0.57
|
0.0 Lesions
Standard Deviation 0.18
|
0.3 Lesions
Standard Deviation 0.65
|
2.7 Lesions
Standard Deviation 3.88
|
3.6 Lesions
Standard Deviation 10.46
|
1.6 Lesions
Standard Deviation 3.74
|
|
Number of Gadolinium (Gd)-Enhanced Lesions
Week 40 (n=78, 84, 82, 28, 24, 25)
|
0.2 Lesions
Standard Deviation 0.67
|
0.1 Lesions
Standard Deviation 0.62
|
0.4 Lesions
Standard Deviation 1.32
|
0.2 Lesions
Standard Deviation 0.42
|
0.3 Lesions
Standard Deviation 1.00
|
0.2 Lesions
Standard Deviation 0.50
|
|
Number of Gadolinium (Gd)-Enhanced Lesions
Week 52 (n=77, 84, 77, 25, 24, 21)
|
0.2 Lesions
Standard Deviation 0.86
|
0.2 Lesions
Standard Deviation 1.23
|
0.4 Lesions
Standard Deviation 0.93
|
0.2 Lesions
Standard Deviation 0.65
|
0.1 Lesions
Standard Deviation 0.34
|
0.4 Lesions
Standard Deviation 0.68
|
|
Number of Gadolinium (Gd)-Enhanced Lesions
Week 100 (n=71, 73, 72, 22, 24, 18)
|
0.1 Lesions
Standard Deviation 0.49
|
0.2 Lesions
Standard Deviation 0.76
|
0.4 Lesions
Standard Deviation 1.37
|
0.2 Lesions
Standard Deviation 0.53
|
0.1 Lesions
Standard Deviation 0.34
|
0.1 Lesions
Standard Deviation 0.47
|
|
Number of Gadolinium (Gd)-Enhanced Lesions
Week 148 (n=61, 67, 68, 18, 22, 18)
|
0.0 Lesions
Standard Deviation 0.22
|
0.1 Lesions
Standard Deviation 0.99
|
0.6 Lesions
Standard Deviation 1.85
|
0.0 Lesions
Standard Deviation 0.00
|
0.2 Lesions
Standard Deviation 0.66
|
0.1 Lesions
Standard Deviation 0.47
|
|
Number of Gadolinium (Gd)-Enhanced Lesions
Early termination (n=16, 14, 13, 6, 3, 6)
|
0.8 Lesions
Standard Deviation 2.76
|
0.1 Lesions
Standard Deviation 0.36
|
1.5 Lesions
Standard Deviation 4.68
|
0.2 Lesions
Standard Deviation 0.41
|
0.0 Lesions
Standard Deviation 0.00
|
0.5 Lesions
Standard Deviation 0.84
|
|
Number of Gadolinium (Gd)-Enhanced Lesions
Week 152 (n=11, 10, 8, 4, 3, 6)
|
0.2 Lesions
Standard Deviation 0.60
|
0.6 Lesions
Standard Deviation 0.97
|
2.5 Lesions
Standard Deviation 6.30
|
0.8 Lesions
Standard Deviation 1.50
|
0.0 Lesions
Standard Deviation 0.00
|
0.3 Lesions
Standard Deviation 0.82
|
|
Number of Gadolinium (Gd)-Enhanced Lesions
Week 200 (n=20, 18, 21, 28, 27, 28)
|
0.0 Lesions
Standard Deviation 0.00
|
0.5 Lesions
Standard Deviation 1.29
|
0.2 Lesions
Standard Deviation 0.89
|
0.0 Lesions
Standard Deviation 0.00
|
0.5 Lesions
Standard Deviation 1.22
|
0.0 Lesions
Standard Deviation 0.00
|
|
Number of Gadolinium (Gd)-Enhanced Lesions
Early Termination 2 (n=58, 61, 60, 17, 21, 16)
|
0.1 Lesions
Standard Deviation 0.34
|
0.2 Lesions
Standard Deviation 0.87
|
0.2 Lesions
Standard Deviation 0.38
|
0.1 Lesions
Standard Deviation 0.33
|
0.2 Lesions
Standard Deviation 0.51
|
0.4 Lesions
Standard Deviation 1.26
|
|
Number of Gadolinium (Gd)-Enhanced Lesions
Week 255 (n=46, 48, 48, 16, 17, 13)
|
1.1 Lesions
Standard Deviation 5.90
|
0.3 Lesions
Standard Deviation 1.01
|
0.4 Lesions
Standard Deviation 1.38
|
1.6 Lesions
Standard Deviation 3.90
|
0.2 Lesions
Standard Deviation 0.53
|
0.3 Lesions
Standard Deviation 0.85
|
|
Number of Gadolinium (Gd)-Enhanced Lesions
End of treatment (n=80, 84, 85, 28, 24, 25)
|
0.1 Lesions
Standard Deviation 0.39
|
0.2 Lesions
Standard Deviation 0.64
|
0.4 Lesions
Standard Deviation 0.93
|
0.2 Lesions
Standard Deviation 0.39
|
0.2 Lesions
Standard Deviation 0.53
|
0.3 Lesions
Standard Deviation 0.50
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
ONO-4641 0.15 mg - 0.15 mg
n=81 Participants
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.
|
ONO-4641 0.10 mg - 0.10 mg
n=87 Participants
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.
|
ONO-4641 0.05 mg - 0.05 mg
n=89 Participants
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.
|
Placebo - ONO4641 0.15 mg
n=28 Participants
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.
|
Placebo - ONO4641 0.10 mg
n=27 Participants
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.
|
Placebo - ONO4641 0.05 mg
n=28 Participants
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.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Lesion Volume at the End of the Treatment (EoT)
|
-0.0264 Cubic centimeter (cc)
Standard Deviation 0.15483
|
0.0294 Cubic centimeter (cc)
Standard Deviation 0.11275
|
0.0197 Cubic centimeter (cc)
Standard Deviation 0.19925
|
-0.4548 Cubic centimeter (cc)
Standard Deviation 0.96555
|
-0.4465 Cubic centimeter (cc)
Standard Deviation 1.22881
|
-0.1105 Cubic centimeter (cc)
Standard Deviation 0.36973
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
ONO-4641 0.15 mg - 0.15 mg
n=81 Participants
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.
|
ONO-4641 0.10 mg - 0.10 mg
n=87 Participants
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.
|
ONO-4641 0.05 mg - 0.05 mg
n=89 Participants
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.
|
Placebo - ONO4641 0.15 mg
n=28 Participants
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.
|
Placebo - ONO4641 0.10 mg
n=27 Participants
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.
|
Placebo - ONO4641 0.05 mg
n=28 Participants
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.
|
|---|---|---|---|---|---|---|
|
Percent Brain Volume Change (PBVC) From Baseline at the End of Treatment
|
-0.845 Percent brain volume
Standard Deviation 0.8745
|
-0.713 Percent brain volume
Standard Deviation 0.8558
|
-0.757 Percent brain volume
Standard Deviation 0.7554
|
-0.756 Percent brain volume
Standard Deviation 0.8239
|
-1.302 Percent brain volume
Standard Deviation 0.9643
|
-0.972 Percent brain volume
Standard Deviation 0.8215
|
Adverse Events
ONO-4641 0.15 Milligram (mg) - 0.15 mg
Serious events: 16 serious events
Other events: 67 other events
Deaths: 0 deaths
ONO-4641 0.10 mg - 0.10 mg
Serious events: 12 serious events
Other events: 80 other events
Deaths: 0 deaths
ONO-4641 0.05 mg - 0.05 mg
Serious events: 21 serious events
Other events: 72 other events
Deaths: 0 deaths
Placebo - ONO4641 0.15 mg
Serious events: 5 serious events
Other events: 21 other events
Deaths: 0 deaths
Placebo - ONO4641 0.10 mg
Serious events: 9 serious events
Other events: 21 other events
Deaths: 0 deaths
Placebo - ONO4641 0.05 mg
Serious events: 11 serious events
Other events: 27 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
ONO-4641 0.15 Milligram (mg) - 0.15 mg
n=80 participants at risk
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.
|
ONO-4641 0.10 mg - 0.10 mg
n=87 participants at risk
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.
|
ONO-4641 0.05 mg - 0.05 mg
n=89 participants at risk
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.
|
Placebo - ONO4641 0.15 mg
n=29 participants at risk
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.
|
Placebo - ONO4641 0.10 mg
n=26 participants at risk
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.
|
Placebo - ONO4641 0.05 mg
n=29 participants at risk
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.
|
|---|---|---|---|---|---|---|
|
Nervous system disorders
Multiple sclerosis relapse
|
5.0%
4/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
9.2%
8/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
12.4%
11/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
23.1%
6/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
20.7%
6/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Nervous system disorders
Paraparesis
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Nervous system disorders
Syncope
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign breast neoplasm
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer in situ
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic gastric cancer
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine cancer
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Infections and infestations
Appendicitis perforated
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Infections and infestations
Encephalitic infection
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Infections and infestations
Lymphangitis
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Infections and infestations
Meningitis aseptic
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Investigations
Blood human chorionic gonadotropin increased
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Gastrointestinal disorders
Colonic polyp
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Gastrointestinal disorders
Gastritis haemorrhagic
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Gastrointestinal disorders
Peritonitis
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
General disorders
Chest pain
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
General disorders
Oedema peripheral
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
General disorders
Pyrexia
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Connective tissue disorder
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Psychiatric disorders
Autism spectrum disorder
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Psychiatric disorders
Mania
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Injury, poisoning and procedural complications
Chemical poisoning
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Injury, poisoning and procedural complications
Fall
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Reproductive system and breast disorders
Pelvic prolapse
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Reproductive system and breast disorders
Uterine polyp
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Surgical and medical procedures
Female sterilisation
|
2.5%
2/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Ear and labyrinth disorders
External ear inflammation
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Eye disorders
Retinal detachment
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Eye disorders
Retinal tear
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Renal and urinary disorders
Nephrolithiasis
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Vascular disorders
Venous insufficiency
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
Other adverse events
| Measure |
ONO-4641 0.15 Milligram (mg) - 0.15 mg
n=80 participants at risk
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.
|
ONO-4641 0.10 mg - 0.10 mg
n=87 participants at risk
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.
|
ONO-4641 0.05 mg - 0.05 mg
n=89 participants at risk
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.
|
Placebo - ONO4641 0.15 mg
n=29 participants at risk
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.
|
Placebo - ONO4641 0.10 mg
n=26 participants at risk
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.
|
Placebo - ONO4641 0.05 mg
n=29 participants at risk
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.
|
|---|---|---|---|---|---|---|
|
Eye disorders
Conjunctival hyperaemia
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
7.7%
2/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Vascular disorders
Hypertension
|
7.5%
6/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.3%
2/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
3/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
15.4%
4/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
17.2%
5/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Ear and labyrinth disorders
Vertigo
|
6.2%
5/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
5.7%
5/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
5.6%
5/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
|
2.5%
2/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
3/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
5.6%
5/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
7.7%
2/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Immune system disorders
Seasonal allergy
|
3.8%
3/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
5.7%
5/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.7%
6/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Cardiac disorders
Palpitations
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
5.7%
5/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.2%
2/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
5.6%
5/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Blood and lymphatic system disorders
Lymphopenia
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
3/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
7.7%
2/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Gastrointestinal disorders
Diarrhoea
|
10.0%
8/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
11.5%
10/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
4.5%
4/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
7.7%
2/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Gastrointestinal disorders
Nausea
|
10.0%
8/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
8.0%
7/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
4.5%
4/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
10.3%
3/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Gastrointestinal disorders
Abdominal pain upper
|
3.8%
3/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
5.7%
5/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
4.5%
4/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Gastrointestinal disorders
Abdominal pain
|
5.0%
4/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.3%
2/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
4.5%
4/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Gastrointestinal disorders
Vomiting
|
5.0%
4/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
4.6%
4/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Gastrointestinal disorders
Dyspepsia
|
5.0%
4/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.3%
2/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.2%
2/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
5.6%
5/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Injury, poisoning and procedural complications
Contusion
|
3.8%
3/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
9.2%
8/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
3/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
7.7%
2/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
17.2%
5/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Injury, poisoning and procedural complications
Fall
|
5.0%
4/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
3/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
3/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
7.7%
2/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
10.3%
3/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Injury, poisoning and procedural complications
Procedural pain
|
5.0%
4/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
4.6%
4/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Injury, poisoning and procedural complications
Muscle strain
|
5.0%
4/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
4.6%
4/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
4.6%
4/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
7.7%
2/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Injury, poisoning and procedural complications
Joint sprain
|
2.5%
2/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.3%
2/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Injury, poisoning and procedural complications
Foreign body in eye
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
7.7%
2/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Psychiatric disorders
Insomnia
|
5.0%
4/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
11.5%
10/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.7%
6/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Psychiatric disorders
Depression
|
5.0%
4/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
8.0%
7/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
5.6%
5/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
13.8%
4/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Psychiatric disorders
Anxiety
|
8.8%
7/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.3%
2/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.2%
2/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Skin and subcutaneous tissue disorders
Acne
|
6.2%
5/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
5.7%
5/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
5.6%
5/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Skin and subcutaneous tissue disorders
Eczema
|
8.8%
7/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
4.6%
4/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Skin and subcutaneous tissue disorders
Increased tendency to bruise
|
2.5%
2/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
8.0%
7/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
3.8%
3/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.3%
2/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
5.7%
5/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
2.5%
2/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.0%
4/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
6/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
9.0%
8/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
7.7%
2/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
10.3%
3/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
8.8%
7/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
3/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.2%
2/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
3.8%
3/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
5.6%
5/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
5.7%
5/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.2%
2/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
General disorders
Fatigue
|
7.5%
6/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
11.5%
10/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
10.1%
9/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
11.5%
3/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
10.3%
3/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
General disorders
Pyrexia
|
3.8%
3/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
4.6%
4/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.7%
6/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
7.7%
2/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Eye disorders
Conjunctivitis
|
2.5%
2/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.7%
6/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Eye disorders
Retinal disorder
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.3%
2/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.2%
2/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Eye disorders
Blepharospasm
|
2.5%
2/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Infections and infestations
Nasopharyngitis
|
22.5%
18/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
24.1%
21/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
24.7%
22/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
10.3%
3/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
30.8%
8/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
24.1%
7/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Infections and infestations
Upper respiratory tract infection
|
17.5%
14/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
24.1%
21/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
16.9%
15/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
13.8%
4/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
19.2%
5/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
20.7%
6/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Infections and infestations
Urinary tract infection
|
8.8%
7/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
18.4%
16/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
14.6%
13/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
15.4%
4/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
20.7%
6/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Infections and infestations
Bronchitis
|
15.0%
12/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
9.2%
8/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
9.0%
8/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Infections and infestations
Oral herpes
|
2.5%
2/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
10.3%
9/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
7.9%
7/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
19.2%
5/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Infections and infestations
Pharyngitis
|
3.8%
3/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
10.3%
9/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.7%
6/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
10.3%
3/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Infections and infestations
Sinusitis
|
10.0%
8/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
6/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
7.9%
7/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
7.7%
2/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Infections and infestations
Influenza
|
3.8%
3/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
6/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
5.6%
5/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
10.3%
3/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Infections and infestations
Gastroenteritis viral
|
5.0%
4/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.3%
2/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.7%
6/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Infections and infestations
Gastroenteritis
|
3.8%
3/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
3/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Infections and infestations
Cystitis
|
3.8%
3/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.2%
2/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
7.7%
2/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.2%
2/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Infections and infestations
Onychomycosis
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Nervous system disorders
Headache
|
16.2%
13/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
14.9%
13/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
14.6%
13/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
24.1%
7/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
19.2%
5/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Nervous system disorders
Multiple sclerosis relapse
|
5.0%
4/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
10.3%
9/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
13.5%
12/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
26.9%
7/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
24.1%
7/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Nervous system disorders
Dizziness
|
5.0%
4/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
9.2%
8/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
3/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Nervous system disorders
Hypoaesthesia
|
6.2%
5/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
3/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
5.6%
5/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Nervous system disorders
Migraine
|
6.2%
5/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
4.6%
4/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
3/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
7.7%
2/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Nervous system disorders
Muscle spasticity
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
5.7%
5/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.2%
2/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Nervous system disorders
Paraesthesia
|
5.0%
4/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.3%
2/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Nervous system disorders
Sciatica
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.3%
2/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
3/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Nervous system disorders
Tremor
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.3%
2/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Nervous system disorders
Memory impairment
|
1.2%
1/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
13.8%
11/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
9.2%
8/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
13.5%
12/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
19.2%
5/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.8%
7/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
9.2%
8/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.7%
6/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
11.5%
3/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
17.2%
5/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
13.8%
11/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
4.6%
4/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
9.0%
8/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
10.3%
3/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.0%
4/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
4.6%
4/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
5.6%
5/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
2.5%
2/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
3/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
5.6%
5/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
2.5%
2/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.3%
2/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
3/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
10.3%
3/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
3.8%
3/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.3%
2/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.7%
6/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
6.9%
2/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.8%
1/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Investigations
Alanine aminotransferase increased
|
10.0%
8/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
9.2%
8/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
13.5%
12/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
20.7%
6/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
11.5%
3/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
20.7%
6/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Investigations
Gamma-glutamyltransferase increased
|
8.8%
7/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
10.3%
9/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
10.1%
9/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
13.8%
4/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
11.5%
3/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
17.2%
5/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Investigations
Aspartate aminotransferase increased
|
3.8%
3/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
4.6%
4/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
4.5%
4/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
10.3%
3/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
13.8%
4/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Investigations
Activated partial thromboplastin time
|
2.5%
2/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
3/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.2%
2/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
7.7%
2/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Investigations
Blood cholesterol increased
|
2.5%
2/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
2.3%
2/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
3/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
7.7%
2/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
3.4%
1/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
|
Investigations
Blood creatine phosphokinase increased
|
3.8%
3/80 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
1.1%
1/87 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
4.5%
4/89 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
7.7%
2/26 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
0.00%
0/29 • From the administration of study medication up to the final study visit, assessed up to 5 years
|
Additional Information
Merck KGaA Communication Center
Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany
Phone: +49-6151-72-5200
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER