Trial Outcomes & Findings for This Was an Open-label, Single-arm Extension Study (CFTY720D2306E1) to a Double-blind, Randomized Multicenter, Placebo-controlled, Parallel-group Core Study (CFTY720D2306) in PPMS. (NCT NCT00731692)
NCT ID: NCT00731692
Last Updated: 2017-06-14
Results Overview
3-month sustained increase from Baseline in EDSS (at least 1 point increase from Baseline for patients with a Baseline value of 5 or less or at least 0.5 point increase from Baseline for patients with a Baseline value of 5.5 or more) or 3-month sustained increase of at least 20% from BL in the time taken to complete the timed 25-foot walk test (25' TWT); or 3-month sustained increase of at least 20% from BL in the time taken to complete the 9-HPT. The 25' TWT is a quantitative measure of lower extremity function. The EDSS is a scale assessing neurologic impairment, including a series of scores in each of 8 functional systems: Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions. The score ranges from 0 (normal) to 10 (death due to MS)). The 9-hole peg test (9-HPT) is a quantitative measure of upper extremity (arm and hand) function.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
970 participants
Primary outcome timeframe
up to 36 months after the last patient was randomized
Results posted on
2017-06-14
Participant Flow
Patients were randomized equally to receive either fingolimod or placebo. Patients initially randomized to fingolimod 1.25 mg/day or matching placebo groups switched in a blinded manner to fingolimod 0.5 mg/day or continued on placebo after amendment in Nov. 2009. Patients were randomized to receive either fingolimod 0.5 mg/day or placebo..
Prior to protocol amendment 147 patients received 1.25mg of FTY720; post protocol amendment 5 not all 147 patients switched to 0.5mg FTY720, only 121 switched and their data is presented under the 0.5mg dose.
Participant milestones
| Measure |
FTY720 1.25 mg to 0.5 mg
Cohort 1: fingolimod 1.25 group consists of patients who were initially randomized to fingolimod 1.25 mg and switched to fingolimod 0.5 mg after amendment
|
FTY720 0.5 mg to 0.5 mg
Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
|
Placebo to -FTY 0.5 mg
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
|---|---|---|---|
|
Core Study (36 Months)
STARTED
|
147
|
336
|
487
|
|
Core Study (36 Months)
Safety Set (SAF)
|
0
|
336
|
487
|
|
Core Study (36 Months)
Full Analysis Set (FAS)
|
0
|
336
|
487
|
|
Core Study (36 Months)
Pharmacokinetic Analysis Set
|
102
|
249
|
0
|
|
Core Study (36 Months)
Post Protocol Amendment 5 Switch
|
0
|
121
|
0
|
|
Core Study (36 Months)
COMPLETED
|
79
|
220
|
317
|
|
Core Study (36 Months)
NOT COMPLETED
|
68
|
116
|
170
|
|
Extension Phase
STARTED
|
74
|
196
|
301
|
|
Extension Phase
COMPLETED
|
0
|
0
|
0
|
|
Extension Phase
NOT COMPLETED
|
74
|
196
|
301
|
Reasons for withdrawal
| Measure |
FTY720 1.25 mg to 0.5 mg
Cohort 1: fingolimod 1.25 group consists of patients who were initially randomized to fingolimod 1.25 mg and switched to fingolimod 0.5 mg after amendment
|
FTY720 0.5 mg to 0.5 mg
Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
|
Placebo to -FTY 0.5 mg
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
|---|---|---|---|
|
Core Study (36 Months)
Lack of Efficacy
|
11
|
23
|
64
|
|
Core Study (36 Months)
Physician Decision
|
1
|
0
|
2
|
|
Core Study (36 Months)
Death
|
2
|
1
|
2
|
|
Core Study (36 Months)
Lost to Follow-up
|
1
|
3
|
3
|
|
Core Study (36 Months)
Administrative
|
2
|
2
|
6
|
|
Core Study (36 Months)
Abnormal Test Procedure Result
|
4
|
3
|
5
|
|
Core Study (36 Months)
Protocol Violation
|
4
|
5
|
8
|
|
Core Study (36 Months)
Abnormal Lab values
|
6
|
19
|
5
|
|
Core Study (36 Months)
Adverse Event
|
25
|
28
|
29
|
|
Core Study (36 Months)
Withdrawal by Subject
|
12
|
32
|
46
|
|
Extension Phase
Admin Problems: Terminated # patients
|
69
|
189
|
277
|
|
Extension Phase
Abnormal test procedure
|
0
|
0
|
1
|
|
Extension Phase
Abnormal lab values
|
0
|
0
|
1
|
|
Extension Phase
Lost to Follow-up
|
0
|
1
|
4
|
|
Extension Phase
Withdrawal by Subject
|
4
|
5
|
3
|
|
Extension Phase
Adverse Event
|
1
|
1
|
15
|
Baseline Characteristics
This Was an Open-label, Single-arm Extension Study (CFTY720D2306E1) to a Double-blind, Randomized Multicenter, Placebo-controlled, Parallel-group Core Study (CFTY720D2306) in PPMS.
Baseline characteristics by cohort
| Measure |
FTY720 1.25 mg to 0.5 mg
n=147 Participants
Cohort 1: fingolimod 1.25 group consists of patients who were initially randomized to fingolimod 1.25 mg and switched to fingolimod 0.5 mg after amendment
|
FTY720 0.5 mg to 0.5 mg
n=336 Participants
Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
|
Placebo
n=487 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
Total
n=970 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
47.8 years
STANDARD_DEVIATION 8.47 • n=5 Participants
|
48.5 years
STANDARD_DEVIATION 8.59 • n=7 Participants
|
48.5 years
STANDARD_DEVIATION 8.31 • n=5 Participants
|
48.5 years
STANDARD_DEVIATION 8.42 • n=4 Participants
|
|
Age, Customized
<=30
|
3 Particpants
n=5 Participants
|
6 Particpants
n=7 Participants
|
4 Particpants
n=5 Participants
|
13 Particpants
n=4 Participants
|
|
Age, Customized
31 to 40
|
22 Particpants
n=5 Participants
|
60 Particpants
n=7 Participants
|
90 Particpants
n=5 Participants
|
172 Particpants
n=4 Participants
|
|
Age, Customized
41 to 50
|
68 Particpants
n=5 Participants
|
127 Particpants
n=7 Participants
|
194 Particpants
n=5 Participants
|
389 Particpants
n=4 Participants
|
|
Age, Customized
>50
|
54 Particpants
n=5 Participants
|
143 Particpants
n=7 Participants
|
199 Particpants
n=5 Participants
|
396 Particpants
n=4 Participants
|
|
Sex: Female, Male
Female
|
71 Participants
n=5 Participants
|
163 Participants
n=7 Participants
|
235 Participants
n=5 Participants
|
469 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
76 Participants
n=5 Participants
|
173 Participants
n=7 Participants
|
252 Participants
n=5 Participants
|
501 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: up to 36 months after the last patient was randomizedPopulation: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo.
3-month sustained increase from Baseline in EDSS (at least 1 point increase from Baseline for patients with a Baseline value of 5 or less or at least 0.5 point increase from Baseline for patients with a Baseline value of 5.5 or more) or 3-month sustained increase of at least 20% from BL in the time taken to complete the timed 25-foot walk test (25' TWT); or 3-month sustained increase of at least 20% from BL in the time taken to complete the 9-HPT. The 25' TWT is a quantitative measure of lower extremity function. The EDSS is a scale assessing neurologic impairment, including a series of scores in each of 8 functional systems: Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions. The score ranges from 0 (normal) to 10 (death due to MS)). The 9-hole peg test (9-HPT) is a quantitative measure of upper extremity (arm and hand) function.
Outcome measures
| Measure |
FTY720 0.5 mg to 0.5 mg
n=336 Participants
Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
|
Placebo
n=487 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
Placebo
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
|---|---|---|---|
|
Kaplan-Meier Estimate of the Risk of 3-month Confirmed Disability Progression Based on Composite Endpoint
|
77.2 Percentage of Participants
Interval 71.87 to 82.51
|
80.3 Percentage of Participants
Interval 73.31 to 87.25
|
—
|
SECONDARY outcome
Timeframe: up to 36 months after the last patient was randomizedPopulation: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo.
The Expanded Disability Status Scale (EDSS) is a scale for assessing neurologic impairment in MS (Kurtzke 1983) and includes a series of scores in each of 8 functional systems and the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions. Fatigue is not included in the Cerebral score of the EDSS. The score ranges from 0 (normal) to 10 (death due to MS)
Outcome measures
| Measure |
FTY720 0.5 mg to 0.5 mg
n=336 Participants
Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
|
Placebo
n=487 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
Placebo
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
|---|---|---|---|
|
Kaplan-Meier Estimate of the Risk of 3- Month Confirmed Disability Progression Based on Expanded Disability Status Scale (EDSS)
|
54.3 Percentage of Participants
Interval 47.16 to 61.45
|
58.7 Percentage of Participants
Interval 53.3 to 64.18
|
—
|
SECONDARY outcome
Timeframe: Baseline to month 36Population: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo. N= Total number of patients included in the analysis.
The percent change from Baseline in brain volume was analyzed using a random coefficients model. The model included: 1) fixed effects: treatment and region and 2) continuous covariates: time, number of Gd enhancing lesions at Baseline, Baseline T2 volume, and normalized brain volume at Baseline. Time as a continuous covariate allowed for the estimation of different slopes and intercepts among treatment groups.
Outcome measures
| Measure |
FTY720 0.5 mg to 0.5 mg
n=293 Participants
Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
|
Placebo
n=421 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
Placebo
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
|---|---|---|---|
|
Percent Change From Baseline in Brain Volume at Month 36
|
-1.49 Percent Change
Interval -1.64 to -1.35
|
-1.53 Percent Change
Interval -1.65 to -1.41
|
—
|
SECONDARY outcome
Timeframe: up to 36 months after the last patient was randomizedPopulation: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo.
The 9-HPT is a quantitative measure of upper extremity (arm and hand) function designed and validated for evaluation of MS patients. N= Total number of patients included in the analysis
Outcome measures
| Measure |
FTY720 0.5 mg to 0.5 mg
n=147 Participants
Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
|
Placebo
n=133 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
Placebo
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
|---|---|---|---|
|
Kaplan Meier Estimate -Percentage of Participants With 3- Month Confirmed Disability Progression Based on 9-HPT.
|
25.0 Percentge of Participants
|
24.9 Percentge of Participants
|
—
|
SECONDARY outcome
Timeframe: up to 36 months after the last patient was randomizedPopulation: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo.
The 25' TWT is a quantitative measure of lower extremity function designed and validated for evaluation of MS patients. N= Total number of patients included in the analysis
Outcome measures
| Measure |
FTY720 0.5 mg to 0.5 mg
n=147 Participants
Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
|
Placebo
n=133 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
Placebo
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
|---|---|---|---|
|
Kaplan Meier Estimate -Percentage of Participants With 3- Month Confirmed Disability Progression Based on 25' TWT.
|
54.8 Percentage of Participants
|
56.7 Percentage of Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline to 36 monthsPopulation: Full analysis set (FAS) -The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo.
Inflammatory disease, as measured by number of new or newly-enlarging T2 lesions, was assessed by Magnetic resonance Imaging (MRI) scanning of the brain and full spinal cord. N= Total number of patients included in the analysis
Outcome measures
| Measure |
FTY720 0.5 mg to 0.5 mg
n=298 Participants
Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
|
Placebo
n=421 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
Placebo
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
|---|---|---|---|
|
Number of New/Enlarging T2 Lesions Per Year Measured From Baseline to Month 36
|
0.13 T2 Lesions per year
Interval 0.1 to 0.18
|
0.50 T2 Lesions per year
Interval 0.4 to 0.61
|
—
|
SECONDARY outcome
Timeframe: Baseline to 36 monthsPopulation: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo.
Inflammatory disease, as measured by number of T1 Gd-enhancing lesions, was assessed by MRI scanning of the brain and full spinal cord. N= Total number of patients included in the analysis
Outcome measures
| Measure |
FTY720 0.5 mg to 0.5 mg
n=223 Participants
Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
|
Placebo
n=320 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
Placebo
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
|---|---|---|---|
|
Number of Gd-enhancing Lesions at Month 36
|
0.05 Gd-enhanced lesions per patient per scan
Interval 0.02 to 0.09
|
0.21 Gd-enhanced lesions per patient per scan
Interval 0.15 to 0.3
|
—
|
SECONDARY outcome
Timeframe: Baseline to month 36Population: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo.
Inflammatory disease as measured by percent change in total T2 lesion volume (mm3) was assessed by MRI. N= Total number of patients included in the analysis
Outcome measures
| Measure |
FTY720 0.5 mg to 0.5 mg
n=224 Participants
Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
|
Placebo
n=326 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
Placebo
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
|---|---|---|---|
|
Percent Change in Total T2 Lesion Volume From Baseline to Month 36
|
-9.2 Percent Change
Standard Deviation 30.55
|
8.9 Percent Change
Standard Deviation 44.13
|
—
|
SECONDARY outcome
Timeframe: Baseline, 36 monthsPopulation: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo. Only subjects with a value at both baseline and at month 36 are included.
The quality of life scale contains 22 items. Each item will be given a score of 1 or 0. A score of 1 (or 0) indicates the presence (or absence) of the symptom or adverse quality of life. All 22 item scores will be summed to obtain a total score ranging from 0 (good) to 22 (poor), which is the PRIMUS QoL scale score
Outcome measures
| Measure |
FTY720 0.5 mg to 0.5 mg
n=66 Participants
Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
|
Placebo
n=150 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
Placebo
n=230 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
|---|---|---|---|
|
Change From Baseline in the Patient Reported Indices in Multiple Sclerosis (PRIMUS-QoL Score)
|
0.2424 Score on a scale
Standard Deviation 4.18444
|
0.5921 Score on a scale
Standard Deviation 4.77704
|
0.9597 Score on a scale
Standard Deviation 4.38578
|
SECONDARY outcome
Timeframe: Baseline, 36 monthsPopulation: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo. Only subjects with a value at both baseline and at month 36 are included.
The activities subscale of PRIMUS contains 15 items and each item is given a score of 0 (able to do on own without difficulties), 1 (able to do on own with difficulties), or 2 (unable to do on own). All 15 items were summed to obtain a total score ranging from 0 (good) to 30 (poor).
Outcome measures
| Measure |
FTY720 0.5 mg to 0.5 mg
n=68 Participants
Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
|
Placebo
n=153 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
Placebo
n=237 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
|---|---|---|---|
|
Change From Baseline in PRIMUS-Activities
|
3.5504 Score on a scale
Standard Deviation 7.05241
|
2.6324 Score on a scale
Standard Deviation 6.22256
|
2.8830 Score on a scale
Standard Deviation 6.76499
|
SECONDARY outcome
Timeframe: Baseline, 36 monthsPopulation: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo. Only subjects with a value at both baseline and at month 36 are included.
Unidimensional Fatigue Impact Scale (U-FIS), contains 22 patient-reported items that assess the impact of fatigue on cognitive, physical, and psychosocial functioning. Responses formed a single unidimensional scale measuring fatigue impact. The U-FIS was calculated and analyzed according to the U-FIS scoring manual. The U-FIS scale contains 22 items with 5 possible outcomes for each item. Two response categories (about half the time and a lot of the time) were combined into 1 category to obtain 4 possible outcomes: 0 (never), 1 (a little of the time), 2 (about half the time/a lot of the time), and 3 (all the time). The 22 condensed item scores were summed to obtain a total score ranging from 0 (no fatigue) to 66 (severe fatigue impact).
Outcome measures
| Measure |
FTY720 0.5 mg to 0.5 mg
n=70 Participants
Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
|
Placebo
n=154 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
Placebo
n=241 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
|---|---|---|---|
|
Change From Baseline in Unidimensional Fatigue Impact (U-FIS) Score
|
1.3197 Score on a scale
Standard Deviation 12.44042
|
2.8451 Score on a scale
Standard Deviation 14.04769
|
3.1394 Score on a scale
Standard Deviation 12.20929
|
SECONDARY outcome
Timeframe: Baseline, 36 monthsPopulation: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo. Only subjects with a value at both baseline and at month 36 are included.
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQoL Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
Outcome measures
| Measure |
FTY720 0.5 mg to 0.5 mg
n=99 Participants
Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
|
Placebo
n=213 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
Placebo
n=320 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
|---|---|---|---|
|
Change From Baseline in European Quality of Life - 5 Dimensions (EQ-5D Score)
|
-0.0332 Score on a scale
Standard Deviation 0.19420
|
-0.0475 Score on a scale
Standard Deviation 0.26099
|
-0.0539 Score on a scale
Standard Deviation 0.22383
|
SECONDARY outcome
Timeframe: Baseline, 36 monthsPopulation: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo. Only subjects with a value at both baseline and at month 36 are included.
The Multiple Sclerosis Walking Scaleis a patient reported measure of walking quality (Hobart et al 2003), consisting of 12 items asking patients to rate the impact of MS upon their walking ability. Responses were captured on a 3-point scale ranging from 1 (Not at all) to 3 (A lot) for items 1 to 3 and on a 5-point scale ranging from 1 (not limited) to 5 (extremely) for items 4 to 12. All 12 item scores were summed to obtain a total score ranging from 12 (good) to 54 (poor) which is the MSWS-12 scale score. The total score was transformed to a 0 to 100 scale score. The MSWS-12 scale score will be transformed to a 0-100 scale score before any summaries or statistical analyses are performed. The transformed score is obtained by subtracting 12 and divided by 42 and multiplying by 100 (i.e., transformed scale score = (raw scale score- 12)/42\*100).
Outcome measures
| Measure |
FTY720 0.5 mg to 0.5 mg
n=75 Participants
Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
|
Placebo
n=182 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
Placebo
n=261 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
|---|---|---|---|
|
Change From Baseline in Multiple Sclerosis Walking Scale (MSWS-12 Score)
|
6.4444 Score on a scale
Standard Deviation 23.81568
|
5.5616 Score on a scale
Standard Deviation 24.59030
|
9.5899 Score on a scale
Standard Deviation 23.98316
|
SECONDARY outcome
Timeframe: Month 3 up to 36 monthsPopulation: Full analysis set (FAS) -The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo. (N). Only participants (n) who provided one or more evaluable blood concentration were included in the pharmacokinetic analysis population. Analysis include 147 patients (cohort 1)
Concentrations of fingolimod and fingolimod-phosphate in whole blood were determined by validated liquid chromatography methods with tandem mass spectrometry. The lower limits of quantification were 0.08 ng/ml for fingolimod and 0.1 ng/ml for fingolimod-phosphate. Venous blood samples were collected for the analysis.
Outcome measures
| Measure |
FTY720 0.5 mg to 0.5 mg
n=102 Participants
Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
|
Placebo
n=102 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
Placebo
n=249 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
|---|---|---|---|
|
Blood Concentrations of Fingolimod and Fingolimod-phosphate
Month 12 Fingolimod (n=23, 161)
|
6.24 ng/ml
Standard Deviation 2.21
|
2.87 ng/ml
Standard Deviation 1.70
|
2.55 ng/ml
Standard Deviation 1.37
|
|
Blood Concentrations of Fingolimod and Fingolimod-phosphate
Month 3 Fingolimod (n=64, 179)
|
6.04 ng/ml
Standard Deviation 3.11
|
NA ng/ml
Standard Deviation NA
No evaluable blood concentration available
|
2.58 ng/ml
Standard Deviation 1.34
|
|
Blood Concentrations of Fingolimod and Fingolimod-phosphate
Month 18 Fingolimod (n=71,155)
|
NA ng/ml
Standard Deviation NA
Patients switched to 0.5mg. No evaluable blood concentration available
|
2.44 ng/ml
Standard Deviation 1.15
|
2.59 ng/ml
Standard Deviation 1.44
|
|
Blood Concentrations of Fingolimod and Fingolimod-phosphate
Month 24 Fingolimod (n=67, 160)
|
NA ng/ml
Standard Deviation NA
Patients switched to 0.5mg. No evaluable blood concentration available
|
2.41 ng/ml
Standard Deviation 1.30
|
2.64 ng/ml
Standard Deviation 1.50
|
|
Blood Concentrations of Fingolimod and Fingolimod-phosphate
Month 30 Fingolimod (n=62, 158)
|
NA ng/ml
Standard Deviation NA
Patients switched to 0.5mg. No evaluable blood concentration available
|
2.52 ng/ml
Standard Deviation 1.28
|
2.60 ng/ml
Standard Deviation 1.33
|
|
Blood Concentrations of Fingolimod and Fingolimod-phosphate
Month 36 Fingolimod (n=55, 118)
|
NA ng/ml
Standard Deviation NA
Patients switched to 0.5mg. No evaluable blood concentration available
|
2.44 ng/ml
Standard Deviation 1.08
|
2.63 ng/ml
Standard Deviation 1.38
|
|
Blood Concentrations of Fingolimod and Fingolimod-phosphate
End of treatment Fingolimod (n=32, 115)
|
NA ng/ml
Standard Deviation NA
Patients switched to 0.5mg. No evaluable blood concentration available
|
2.02 ng/ml
Standard Deviation 1.10
|
2.57 ng/ml
Standard Deviation 1.51
|
|
Blood Concentrations of Fingolimod and Fingolimod-phosphate
Month 3 Fingolimod-Phosphate (n=64, 179)
|
3.20 ng/ml
Standard Deviation 1.73
|
NA ng/ml
Standard Deviation NA
No evaluable blood concentration available
|
1.40 ng/ml
Standard Deviation 0.747
|
|
Blood Concentrations of Fingolimod and Fingolimod-phosphate
Month 12 Fingolimod-Phosphate (n=23, 161)
|
3.21 ng/ml
Standard Deviation 1.16
|
1.54 ng/ml
Standard Deviation 0.871
|
1.43 ng/ml
Standard Deviation 0.805
|
|
Blood Concentrations of Fingolimod and Fingolimod-phosphate
Month 18 Fingolimod-Phosphate (n=71,155)
|
NA ng/ml
Standard Deviation NA
Patients switched to 0.5mg. No evaluable blood concentration available
|
1.34 ng/ml
Standard Deviation 0.630
|
1.41 ng/ml
Standard Deviation 0.758
|
|
Blood Concentrations of Fingolimod and Fingolimod-phosphate
Month 24 Fingolimod-Phosphate (n=67, 160)
|
NA ng/ml
Standard Deviation NA
Patients switched to 0.5mg. No evaluable blood concentration available
|
1.35 ng/ml
Standard Deviation 0.765
|
1.44 ng/ml
Standard Deviation 0.790
|
|
Blood Concentrations of Fingolimod and Fingolimod-phosphate
Month 30 Fingolimod-Phosphate (n=62, 158)
|
NA ng/ml
Standard Deviation NA
Patients switched to 0.5mg. No evaluable blood concentration available
|
1.32 ng/ml
Standard Deviation 0.676
|
1.48 ng/ml
Standard Deviation 0.759
|
|
Blood Concentrations of Fingolimod and Fingolimod-phosphate
Month 36 Fingolimod-Phosphate (n=55, 118)
|
NA ng/ml
Standard Deviation NA
Patients switched to 0.5mg. No evaluable blood concentration available
|
1.32 ng/ml
Standard Deviation 0.591
|
1.51 ng/ml
Standard Deviation 0.765
|
|
Blood Concentrations of Fingolimod and Fingolimod-phosphate
End of treatment Fingolimod-Phosphate (n=32, 115
|
NA ng/ml
Standard Deviation NA
Patients switched to 0.5mg. No evaluable blood concentration available
|
1.19 ng/ml
Standard Deviation 0.618
|
1.50 ng/ml
Standard Deviation 0.900
|
SECONDARY outcome
Timeframe: Baseline to Month 36Population: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS
The Multiple Sclerosis Functional Composite (MSFC) is a multidimensional clinical outcome measure that includes quantitative tests of leg function/ambulation (Timed 25-Foot Walk), arm function (9-Hole Peg Test), and cognitive function (Paced Auditory Serial Addition Test). The overall MSFC z-score as an average of the three standardized scores derived using baseline data pooled over each treatment arm as reference population. Higher scores reflect better neurological function and a positive change from Baseline indicates improvement.
Outcome measures
| Measure |
FTY720 0.5 mg to 0.5 mg
n=193 Participants
Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
|
Placebo
n=279 Participants
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
Placebo
Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
|
|---|---|---|---|
|
Change in MSFC Z-score and Subscale Scores From Baseline to Month 36
|
-0.189 Z-scores
Standard Deviation 0.6980
|
-0.212 Z-scores
Standard Deviation 0.8468
|
—
|
Adverse Events
Core: FTY720 1.25 mg
Serious events: 38 serious events
Other events: 132 other events
Deaths: 0 deaths
Core: FTY720 0.5 mg
Serious events: 84 serious events
Other events: 278 other events
Deaths: 0 deaths
Core: Placebo
Serious events: 117 serious events
Other events: 406 other events
Deaths: 0 deaths
Extension: FTY1.25-0.5
Serious events: 7 serious events
Other events: 43 other events
Deaths: 0 deaths
Extension: FTY0.5-0.5
Serious events: 10 serious events
Other events: 70 other events
Deaths: 0 deaths
Extension: Placebo-FTY0.5
Serious events: 37 serious events
Other events: 138 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Core: FTY720 1.25 mg
n=147 participants at risk
Patients who received FTY720 1.25 mg during core
|
Core: FTY720 0.5 mg
n=336 participants at risk
Patients who received FTY720 0.5 mg during core
|
Core: Placebo
n=487 participants at risk
Patients who received Placebo during core
|
Extension: FTY1.25-0.5
n=74 participants at risk
Patients who received FTY20 1.25 mg in core and received 0.5 mg of FTY during Extension
|
Extension: FTY0.5-0.5
n=196 participants at risk
Patients who received FTY20 0.5 mg in core and received 0.5 mg of FTY during Extension
|
Extension: Placebo-FTY0.5
n=301 participants at risk
Patients who received Placebo in core and received 0.5 mg of FTY during Extension
|
|---|---|---|---|---|---|---|
|
Infections and infestations
Cellulitis
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
1.4%
1/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Cystitis
|
0.68%
1/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.51%
1/196
|
0.00%
0/301
|
|
Blood and lymphatic system disorders
Anaemia macrocytic
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.68%
1/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.51%
1/196
|
0.00%
0/301
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Cardiac disorders
Atrioventricular block
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Cardiac disorders
Atrioventricular block complete
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Cardiac disorders
Atrioventricular block first degree
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Cardiac disorders
Atrioventricular block second degree
|
0.68%
1/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Cardiac disorders
Bradycardia
|
1.4%
2/147
|
0.60%
2/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Cardiac disorders
Myocardial infarction
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Cardiac disorders
Myocardial ischaemia
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Cardiac disorders
Pericarditis
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Cardiac disorders
Sinus bradycardia
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Cardiac disorders
Tachycardia paroxysmal
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Eye disorders
Amblyopia strabismic
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Eye disorders
Angle closure glaucoma
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Eye disorders
Cataract cortical
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Eye disorders
Chorioretinopathy
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Eye disorders
Cystoid macular oedema
|
0.00%
0/147
|
0.30%
1/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Eye disorders
Diplopia
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Eye disorders
Intraocular haematoma
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Eye disorders
Macular oedema
|
0.68%
1/147
|
1.2%
4/336
|
0.82%
4/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Eye disorders
Myopia
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Eye disorders
Optic atrophy
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Eye disorders
Retinal detachment
|
0.00%
0/147
|
0.30%
1/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Eye disorders
Retinal tear
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Gastrointestinal disorders
Anal polyp
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Gastrointestinal disorders
Colitis ulcerative
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/147
|
0.60%
2/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Gastrointestinal disorders
Faecaloma
|
0.00%
0/147
|
0.30%
1/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.68%
1/147
|
0.00%
0/336
|
0.41%
2/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Gastrointestinal disorders
Obstruction gastric
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
General disorders
Asthenia
|
0.68%
1/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
General disorders
Chest discomfort
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
General disorders
Device dislocation
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
General disorders
Device occlusion
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
General disorders
Drug ineffective
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
General disorders
Fatigue
|
0.00%
0/147
|
0.30%
1/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
General disorders
Gait disturbance
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
General disorders
General physical health deterioration
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
General disorders
Pyrexia
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Hepatobiliary disorders
Cholecystitis
|
0.68%
1/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/147
|
0.30%
1/336
|
0.62%
3/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Hepatobiliary disorders
Cholelithiasis obstructive
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Appendicitis
|
0.68%
1/147
|
0.00%
0/336
|
0.41%
2/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Bacterial infection
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Infections and infestations
Blister infected
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Bronchitis viral
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Bursitis infective
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
1.4%
1/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Dengue fever
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/147
|
0.00%
0/336
|
0.41%
2/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Enterocolitis bacterial
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Epididymitis
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/147
|
0.60%
2/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
H1N1 influenza
|
0.00%
0/147
|
0.00%
0/336
|
0.41%
2/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Herpes zoster
|
0.68%
1/147
|
0.60%
2/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Herpes zoster infection neurological
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Herpes zoster meningomyelitis
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Incision site infection
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Infection
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Infectious pleural effusion
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Influenza
|
0.00%
0/147
|
0.89%
3/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Infections and infestations
Meningitis
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Myelitis
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Ophthalmic herpes simplex
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Peritonitis
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Infections and infestations
Pneumonia
|
1.4%
2/147
|
1.2%
4/336
|
0.41%
2/487
|
1.4%
1/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Infections and infestations
Pulmonary sepsis
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/147
|
0.00%
0/336
|
0.62%
3/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Respiratory tract infection
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Septic shock
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Serratia sepsis
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Subcutaneous abscess
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
1.4%
1/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Systemic mycosis
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Tonsillitis
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Tracheobronchitis
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Urinary tract infection
|
1.4%
2/147
|
2.4%
8/336
|
2.5%
12/487
|
1.4%
1/74
|
0.00%
0/196
|
1.3%
4/301
|
|
Infections and infestations
Urinary tract infection bacterial
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Urosepsis
|
0.68%
1/147
|
0.00%
0/336
|
0.41%
2/487
|
0.00%
0/74
|
0.51%
1/196
|
0.00%
0/301
|
|
Infections and infestations
Viral infection
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Alcohol poisoning
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.51%
1/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Concussion
|
0.68%
1/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Facial bones fracture
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.51%
1/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Fall
|
2.0%
3/147
|
0.30%
1/336
|
0.62%
3/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.68%
1/147
|
0.30%
1/336
|
0.62%
3/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Fracture displacement
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/147
|
0.30%
1/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.68%
1/147
|
0.00%
0/336
|
0.41%
2/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.68%
1/147
|
0.00%
0/336
|
0.41%
2/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Laceration
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Limb traumatic amputation
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Meniscus injury
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Injury, poisoning and procedural complications
Pneumothorax traumatic
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Post procedural complication
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Injury, poisoning and procedural complications
Post procedural haematoma
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.68%
1/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Skull fracture
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Injury, poisoning and procedural complications
Traumatic renal injury
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Wound
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/147
|
0.00%
0/336
|
0.41%
2/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/147
|
0.00%
0/336
|
0.41%
2/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Investigations
Blood pressure increased
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Investigations
Foetal heart rate abnormal
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Investigations
International normalised ratio decreased
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
1.4%
1/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Investigations
Troponin increased
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Investigations
Weight decreased
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/147
|
0.30%
1/336
|
0.41%
2/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Metabolism and nutrition disorders
Polydipsia
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/147
|
0.30%
1/336
|
0.41%
2/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.66%
2/301
|
|
Musculoskeletal and connective tissue disorders
Bone swelling
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
1.4%
1/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Musculoskeletal and connective tissue disorders
Mobility decreased
|
0.00%
0/147
|
0.00%
0/336
|
0.41%
2/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/147
|
0.00%
0/336
|
0.41%
2/487
|
1.4%
1/74
|
0.00%
0/196
|
0.66%
2/301
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Musculoskeletal and connective tissue disorders
Osteopenia
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.00%
0/147
|
0.00%
0/336
|
0.41%
2/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Musculoskeletal and connective tissue disorders
Sjogren's syndrome
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Musculoskeletal and connective tissue disorders
Spinal column stenosis
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Musculoskeletal and connective tissue disorders
Tendon disorder
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.68%
1/147
|
3.3%
11/336
|
1.8%
9/487
|
1.4%
1/74
|
1.0%
2/196
|
0.33%
1/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
1.4%
2/147
|
0.30%
1/336
|
0.00%
0/487
|
1.4%
1/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Dysplastic naevus
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibrous histiocytoma
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive ductal breast carcinoma
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive lobular breast carcinoma
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphocytic leukaemia
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma in situ
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Medullary thyroid cancer
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to kidney
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-Hodgkin's lymphoma
|
0.68%
1/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Osteoma
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian cancer metastatic
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/147
|
0.30%
1/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small cell lung cancer metastatic
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
0.00%
0/147
|
1.8%
6/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Aphasia
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Arachnoiditis
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Brain oedema
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Central nervous system lesion
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/147
|
0.00%
0/336
|
0.41%
2/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Cerebrovascular disorder
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
1.4%
1/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Nervous system disorders
Generalised tonic-clonic seizure
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Monoparesis
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Multiple sclerosis
|
1.4%
2/147
|
0.89%
3/336
|
1.0%
5/487
|
0.00%
0/74
|
0.00%
0/196
|
0.66%
2/301
|
|
Nervous system disorders
Multiple sclerosis relapse
|
0.00%
0/147
|
0.30%
1/336
|
1.0%
5/487
|
0.00%
0/74
|
0.00%
0/196
|
0.66%
2/301
|
|
Nervous system disorders
Muscle spasticity
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Myelitis transverse
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Neuralgia
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Nystagmus
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Optic neuritis
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Paraparesis
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Peroneal nerve palsy
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Presyncope
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Primary progressive multiple sclerosis
|
0.68%
1/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Progressive multiple sclerosis
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.51%
1/196
|
0.00%
0/301
|
|
Nervous system disorders
Quadriparesis
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Sciatica
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Seizure
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.51%
1/196
|
0.00%
0/301
|
|
Nervous system disorders
Status epilepticus
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Syncope
|
0.00%
0/147
|
0.00%
0/336
|
0.41%
2/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/147
|
0.30%
1/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
Trigeminal neuralgia
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Nervous system disorders
Uhthoff's phenomenon
|
1.4%
2/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Nervous system disorders
VIIth nerve paralysis
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Psychiatric disorders
Adjustment disorder
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Psychiatric disorders
Aggression
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Psychiatric disorders
Depression
|
0.00%
0/147
|
0.00%
0/336
|
0.41%
2/487
|
0.00%
0/74
|
0.51%
1/196
|
0.00%
0/301
|
|
Psychiatric disorders
Depressive symptom
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Psychiatric disorders
Mania
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Psychiatric disorders
Mood swings
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Psychiatric disorders
Panic attack
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Psychiatric disorders
Psychotic disorder
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/147
|
0.30%
1/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/147
|
0.30%
1/336
|
0.41%
2/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Renal and urinary disorders
Bladder neck sclerosis
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Renal and urinary disorders
Nephrogenic diabetes insipidus
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.68%
1/147
|
0.60%
2/336
|
0.21%
1/487
|
0.00%
0/74
|
0.51%
1/196
|
0.00%
0/301
|
|
Renal and urinary disorders
Neurogenic bladder
|
0.68%
1/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Renal and urinary disorders
Polyuria
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Renal and urinary disorders
Urethral obstruction
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.51%
1/196
|
0.00%
0/301
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/147
|
0.60%
2/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Reproductive system and breast disorders
Adenomyosis
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Reproductive system and breast disorders
Adnexal torsion
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.00%
0/147
|
0.30%
1/336
|
0.41%
2/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Reproductive system and breast disorders
Breast mass
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Reproductive system and breast disorders
Endometriosis
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Reproductive system and breast disorders
Prostatitis
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Reproductive system and breast disorders
Prostatomegaly
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopneumopathy
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/147
|
0.60%
2/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Respiratory, thoracic and mediastinal disorders
Haemothorax
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Respiratory, thoracic and mediastinal disorders
Nasal obstruction
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.68%
1/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Skin and subcutaneous tissue disorders
Actinic keratosis
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
0.68%
1/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Skin and subcutaneous tissue disorders
Jessner's lymphocytic infiltration
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Skin and subcutaneous tissue disorders
Lentigo
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Social circumstances
Activities of daily living impaired
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Social circumstances
Poor personal hygiene
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Vascular disorders
Aneurysm
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Vascular disorders
Arterial spasm
|
0.00%
0/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Vascular disorders
Deep vein thrombosis
|
0.68%
1/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Vascular disorders
Femoral artery occlusion
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Vascular disorders
Hypotension
|
0.68%
1/147
|
0.00%
0/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Vascular disorders
Peripheral venous disease
|
0.00%
0/147
|
1.2%
4/336
|
0.41%
2/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Vascular disorders
Raynaud's phenomenon
|
0.00%
0/147
|
0.30%
1/336
|
0.00%
0/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
|
Vascular disorders
Venous thrombosis
|
0.00%
0/147
|
0.00%
0/336
|
0.21%
1/487
|
0.00%
0/74
|
0.00%
0/196
|
0.00%
0/301
|
Other adverse events
| Measure |
Core: FTY720 1.25 mg
n=147 participants at risk
Patients who received FTY720 1.25 mg during core
|
Core: FTY720 0.5 mg
n=336 participants at risk
Patients who received FTY720 0.5 mg during core
|
Core: Placebo
n=487 participants at risk
Patients who received Placebo during core
|
Extension: FTY1.25-0.5
n=74 participants at risk
Patients who received FTY20 1.25 mg in core and received 0.5 mg of FTY during Extension
|
Extension: FTY0.5-0.5
n=196 participants at risk
Patients who received FTY20 0.5 mg in core and received 0.5 mg of FTY during Extension
|
Extension: Placebo-FTY0.5
n=301 participants at risk
Patients who received Placebo in core and received 0.5 mg of FTY during Extension
|
|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Lymphopenia
|
8.8%
13/147
|
5.7%
19/336
|
0.00%
0/487
|
5.4%
4/74
|
3.6%
7/196
|
3.7%
11/301
|
|
Gastrointestinal disorders
Abdominal pain upper
|
2.0%
3/147
|
5.1%
17/336
|
2.5%
12/487
|
0.00%
0/74
|
0.51%
1/196
|
0.66%
2/301
|
|
Gastrointestinal disorders
Constipation
|
6.8%
10/147
|
8.0%
27/336
|
7.2%
35/487
|
0.00%
0/74
|
1.0%
2/196
|
2.0%
6/301
|
|
Gastrointestinal disorders
Diarrhoea
|
8.8%
13/147
|
4.5%
15/336
|
3.7%
18/487
|
1.4%
1/74
|
1.5%
3/196
|
0.33%
1/301
|
|
Gastrointestinal disorders
Nausea
|
9.5%
14/147
|
6.2%
21/336
|
3.9%
19/487
|
2.7%
2/74
|
0.51%
1/196
|
1.3%
4/301
|
|
General disorders
Fatigue
|
10.9%
16/147
|
7.1%
24/336
|
8.8%
43/487
|
0.00%
0/74
|
0.51%
1/196
|
3.0%
9/301
|
|
General disorders
Gait disturbance
|
6.8%
10/147
|
4.5%
15/336
|
4.9%
24/487
|
0.00%
0/74
|
0.51%
1/196
|
0.00%
0/301
|
|
General disorders
Pyrexia
|
5.4%
8/147
|
5.4%
18/336
|
4.1%
20/487
|
4.1%
3/74
|
0.00%
0/196
|
1.3%
4/301
|
|
Infections and infestations
Bronchitis
|
6.8%
10/147
|
4.8%
16/336
|
4.3%
21/487
|
4.1%
3/74
|
1.0%
2/196
|
0.33%
1/301
|
|
Infections and infestations
Cystitis
|
6.8%
10/147
|
2.7%
9/336
|
3.5%
17/487
|
0.00%
0/74
|
0.00%
0/196
|
0.66%
2/301
|
|
Infections and infestations
Gastroenteritis
|
6.8%
10/147
|
3.6%
12/336
|
4.5%
22/487
|
0.00%
0/74
|
1.5%
3/196
|
1.00%
3/301
|
|
Infections and infestations
Influenza
|
9.5%
14/147
|
7.7%
26/336
|
8.8%
43/487
|
4.1%
3/74
|
2.0%
4/196
|
3.0%
9/301
|
|
Infections and infestations
Nasopharyngitis
|
27.2%
40/147
|
23.2%
78/336
|
27.7%
135/487
|
12.2%
9/74
|
5.1%
10/196
|
7.6%
23/301
|
|
Infections and infestations
Upper respiratory tract infection
|
14.3%
21/147
|
11.0%
37/336
|
11.7%
57/487
|
8.1%
6/74
|
3.1%
6/196
|
4.7%
14/301
|
|
Infections and infestations
Urinary tract infection
|
14.3%
21/147
|
14.0%
47/336
|
15.4%
75/487
|
5.4%
4/74
|
5.6%
11/196
|
8.3%
25/301
|
|
Injury, poisoning and procedural complications
Fall
|
21.1%
31/147
|
14.0%
47/336
|
18.7%
91/487
|
8.1%
6/74
|
2.6%
5/196
|
4.3%
13/301
|
|
Investigations
Alanine aminotransferase increased
|
11.6%
17/147
|
11.6%
39/336
|
1.4%
7/487
|
0.00%
0/74
|
0.51%
1/196
|
2.0%
6/301
|
|
Investigations
Blood cholesterol increased
|
5.4%
8/147
|
4.5%
15/336
|
3.3%
16/487
|
0.00%
0/74
|
0.51%
1/196
|
1.00%
3/301
|
|
Investigations
Gamma-glutamyltransferase increased
|
12.9%
19/147
|
9.2%
31/336
|
0.62%
3/487
|
0.00%
0/74
|
1.5%
3/196
|
1.7%
5/301
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
6.8%
10/147
|
3.9%
13/336
|
3.9%
19/487
|
5.4%
4/74
|
2.0%
4/196
|
1.7%
5/301
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.8%
13/147
|
8.9%
30/336
|
9.9%
48/487
|
4.1%
3/74
|
1.5%
3/196
|
2.7%
8/301
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.9%
16/147
|
10.7%
36/336
|
15.4%
75/487
|
6.8%
5/74
|
2.6%
5/196
|
3.3%
10/301
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.1%
9/147
|
6.2%
21/336
|
7.2%
35/487
|
4.1%
3/74
|
1.5%
3/196
|
1.00%
3/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
|
14.3%
21/147
|
4.8%
16/336
|
6.4%
31/487
|
5.4%
4/74
|
1.5%
3/196
|
3.0%
9/301
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis
|
6.8%
10/147
|
3.6%
12/336
|
2.9%
14/487
|
1.4%
1/74
|
1.5%
3/196
|
1.3%
4/301
|
|
Nervous system disorders
Dizziness
|
6.8%
10/147
|
5.7%
19/336
|
6.0%
29/487
|
2.7%
2/74
|
0.00%
0/196
|
0.66%
2/301
|
|
Nervous system disorders
Headache
|
19.0%
28/147
|
16.7%
56/336
|
15.8%
77/487
|
4.1%
3/74
|
1.5%
3/196
|
4.3%
13/301
|
|
Psychiatric disorders
Depression
|
7.5%
11/147
|
4.5%
15/336
|
7.6%
37/487
|
2.7%
2/74
|
1.0%
2/196
|
1.3%
4/301
|
|
Psychiatric disorders
Insomnia
|
5.4%
8/147
|
3.6%
12/336
|
6.0%
29/487
|
1.4%
1/74
|
2.0%
4/196
|
2.3%
7/301
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.4%
8/147
|
8.3%
28/336
|
7.0%
34/487
|
2.7%
2/74
|
0.51%
1/196
|
1.3%
4/301
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.4%
8/147
|
4.2%
14/336
|
3.3%
16/487
|
0.00%
0/74
|
0.00%
0/196
|
0.33%
1/301
|
|
Skin and subcutaneous tissue disorders
Eczema
|
5.4%
8/147
|
4.5%
15/336
|
3.9%
19/487
|
2.7%
2/74
|
0.51%
1/196
|
2.0%
6/301
|
|
Vascular disorders
Hypertension
|
15.6%
23/147
|
12.8%
43/336
|
5.7%
28/487
|
2.7%
2/74
|
2.6%
5/196
|
6.0%
18/301
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
- Publication restrictions are in place
Restriction type: OTHER