Trial Outcomes & Findings for A Study of CAD106 and CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease (NCT NCT02565511)
NCT ID: NCT02565511
Last Updated: 2021-07-08
Results Overview
Event was defined as the first confirmed diagnosis of MCI due to Alzheimer's disease (AD) or dementia due to AD (whichever occurred first) after adjudication by the progression adjudication committee (PAC) as triggered either by an investigator diagnosis or an increase in the Clinical Dementia Rating (CDR) global score. An event had to be confirmed by the PAC at two consecutive visits. In case no confirmed event was observed for a participant, the observation was censored, and the censoring date was defined as the last date where the diagnostic classification was assessed. The Study was terminated and only confirmed events collected up to the data cut-off point were counted. Due to the early termination of the study only a small number of events were observed and time-to-event could not be analyzed. Kaplan-Meyer (KM) estimates were provided to estimate probability that a subject would have an event prior to the specified visit.
Recruitment status
TERMINATED
Study phase
PHASE2/PHASE3
Target enrollment
480 participants
Primary outcome timeframe
Baseline to end of exposure for a maximum of 1455 days for CI and 907 days for CII
Results posted on
2021-07-08
Participant Flow
713 participants were screened
Participant milestones
| Measure |
Cohort I (CI) CAD106
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort I (CI) CAD106 Placebo
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort II (CII) CNP520
CNP520 (50 mg) capsules taken once daily orally
|
Cohort II (CII) CNP520 Placebo
Placebo to CNP520 capsules taken once daily orally
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
42
|
23
|
251
|
164
|
|
Overall Study
3 Patients Were Mis-randomized
|
0
|
0
|
2
|
1
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
42
|
23
|
251
|
164
|
Reasons for withdrawal
| Measure |
Cohort I (CI) CAD106
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort I (CI) CAD106 Placebo
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort II (CII) CNP520
CNP520 (50 mg) capsules taken once daily orally
|
Cohort II (CII) CNP520 Placebo
Placebo to CNP520 capsules taken once daily orally
|
|---|---|---|---|---|
|
Overall Study
Study terminated by Sponsor
|
35
|
22
|
235
|
156
|
|
Overall Study
Withdrawal by Subject
|
3
|
0
|
12
|
5
|
|
Overall Study
Adverse Event
|
0
|
0
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
4
|
1
|
0
|
1
|
|
Overall Study
Physician Decision
|
0
|
0
|
0
|
1
|
|
Overall Study
Protocol deviation
|
0
|
0
|
3
|
0
|
Baseline Characteristics
Numbers in row represent participants in either Cohort I or Cohort II
Baseline characteristics by cohort
| Measure |
Cohort I (CI) CAD106
n=42 Participants
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort I (CI) CAD106 Placebo
n=23 Participants
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort II (CII) CNP520
n=249 Participants
CNP520 (50 mg) capsules taken once daily orally
|
Cohort II (CII) CNP520 Placebo
n=163 Participants
Placebo to CNP520 capsules taken once daily orally
|
Total
n=477 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Cohort II API Preclinical Composite Cognitive Battery (APCC)
|
—
|
—
|
29.0 scores on a scale
STANDARD_DEVIATION 1.17 • n=249 Participants • Numbers in row represent participants in either Cohort I or Cohort II
|
28.9 scores on a scale
STANDARD_DEVIATION 1.33 • n=163 Participants • Numbers in row represent participants in either Cohort I or Cohort II
|
29.0 scores on a scale
STANDARD_DEVIATION 1.23 • n=412 Participants • Numbers in row represent participants in either Cohort I or Cohort II
|
|
Age, Customized
<=64 years
|
20 participants
n=42 Participants
|
9 participants
n=23 Participants
|
77 participants
n=249 Participants
|
52 participants
n=163 Participants
|
158 participants
n=477 Participants
|
|
Age, Customized
65-69 years
|
18 participants
n=42 Participants
|
7 participants
n=23 Participants
|
116 participants
n=249 Participants
|
65 participants
n=163 Participants
|
206 participants
n=477 Participants
|
|
Age, Customized
>70 years
|
4 participants
n=42 Participants
|
7 participants
n=23 Participants
|
56 participants
n=249 Participants
|
46 participants
n=163 Participants
|
113 participants
n=477 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=42 Participants
|
17 Participants
n=23 Participants
|
129 Participants
n=249 Participants
|
102 Participants
n=163 Participants
|
275 Participants
n=477 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=42 Participants
|
6 Participants
n=23 Participants
|
120 Participants
n=249 Participants
|
61 Participants
n=163 Participants
|
202 Participants
n=477 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
41 participants
n=42 Participants
|
22 participants
n=23 Participants
|
241 participants
n=249 Participants
|
162 participants
n=163 Participants
|
466 participants
n=477 Participants
|
|
Race/Ethnicity, Customized
Black
|
1 participants
n=42 Participants
|
1 participants
n=23 Participants
|
1 participants
n=249 Participants
|
0 participants
n=163 Participants
|
3 participants
n=477 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 participants
n=42 Participants
|
0 participants
n=23 Participants
|
4 participants
n=249 Participants
|
0 participants
n=163 Participants
|
4 participants
n=477 Participants
|
|
Race/Ethnicity, Customized
Pacific Islander
|
0 participants
n=42 Participants
|
0 participants
n=23 Participants
|
1 participants
n=249 Participants
|
0 participants
n=163 Participants
|
1 participants
n=477 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 participants
n=42 Participants
|
0 participants
n=23 Participants
|
1 participants
n=249 Participants
|
0 participants
n=163 Participants
|
1 participants
n=477 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
0 participants
n=42 Participants
|
0 participants
n=23 Participants
|
1 participants
n=249 Participants
|
1 participants
n=163 Participants
|
2 participants
n=477 Participants
|
|
Cohort I API Preclinical Composite Cognitive Battery (APCC)
|
78.0 Scores on a scale
STANDARD_DEVIATION 5.53 • n=42 Participants • Numbers in row represent participants in either Cohort I or Cohort II
|
79.0 Scores on a scale
STANDARD_DEVIATION 6.76 • n=23 Participants • Numbers in row represent participants in either Cohort I or Cohort II
|
—
|
—
|
78.3 Scores on a scale
STANDARD_DEVIATION 5.96 • n=65 Participants • Numbers in row represent participants in either Cohort I or Cohort II
|
|
Cohort I Repeatable Battery for Assessment of Neurological Status (RBANS)
|
104.4 Scores on a scale
STANDARD_DEVIATION 12.03 • n=42 Participants • Numbers in row represent participants in either Cohort I or Cohort II
|
108.7 Scores on a scale
STANDARD_DEVIATION 12.83 • n=23 Participants • Numbers in row represent participants in either Cohort I or Cohort II
|
—
|
—
|
106.0 Scores on a scale
STANDARD_DEVIATION 12.39 • n=65 Participants • Numbers in row represent participants in either Cohort I or Cohort II
|
|
Cohort I Clinical Dementia Rating Sum of Boxes (CDR-SOB)
|
0.10 scores on a scale
STANDARD_DEVIATION 0.276 • n=42 Participants • Numbers in row represent participants in either Cohort I or Cohort II
|
0.04 scores on a scale
STANDARD_DEVIATION 0.209 • n=23 Participants • Numbers in row represent participants in either Cohort I or Cohort II
|
—
|
—
|
0.08 scores on a scale
STANDARD_DEVIATION 0.254 • n=65 Participants • Numbers in row represent participants in either Cohort I or Cohort II
|
|
Cohort II Repeatable Battery for Assessment of Neurological Status (RBANS)
|
—
|
—
|
102.6 scores on a scale
STANDARD_DEVIATION 12.22 • n=249 Participants • Numbers in row represent participants in either Cohort I or Cohort II
|
103.2 scores on a scale
STANDARD_DEVIATION 12.03 • n=163 Participants • Numbers in row represent participants in either Cohort I or Cohort II
|
102.9 scores on a scale
STANDARD_DEVIATION 12.13 • n=412 Participants • Numbers in row represent participants in either Cohort I or Cohort II
|
|
Cohort II Clinical Dementia Rating Sum of Boxes (CDR-SOB)
|
—
|
—
|
0.16 scores on a scale
STANDARD_DEVIATION 0.15 • n=249 Participants • Numbers in row represent participants in either Cohort I or Cohort II
|
0.15 scores on a scale
STANDARD_DEVIATION 0.417 • n=163 Participants • Numbers in row represent participants in either Cohort I or Cohort II
|
0.16 scores on a scale
STANDARD_DEVIATION 0.409 • n=412 Participants • Numbers in row represent participants in either Cohort I or Cohort II
|
PRIMARY outcome
Timeframe: Baseline to end of exposure for a maximum of 1455 days for CI and 907 days for CIIPopulation: n=number of participants at risk to experience an event at the time-point
Event was defined as the first confirmed diagnosis of MCI due to Alzheimer's disease (AD) or dementia due to AD (whichever occurred first) after adjudication by the progression adjudication committee (PAC) as triggered either by an investigator diagnosis or an increase in the Clinical Dementia Rating (CDR) global score. An event had to be confirmed by the PAC at two consecutive visits. In case no confirmed event was observed for a participant, the observation was censored, and the censoring date was defined as the last date where the diagnostic classification was assessed. The Study was terminated and only confirmed events collected up to the data cut-off point were counted. Due to the early termination of the study only a small number of events were observed and time-to-event could not be analyzed. Kaplan-Meyer (KM) estimates were provided to estimate probability that a subject would have an event prior to the specified visit.
Outcome measures
| Measure |
Cohort I (CI) CAD106
n=41 Participants
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort I (CI) CAD106 Placebo
n=22 Participants
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort II (CII) CNP520
n=193 Participants
CNP520 (50 mg) capsules taken once daily orally
|
Cohort II (CII) CNP520 Placebo
n=126 Participants
Placebo to CNP520 capsules taken once daily orally
|
|---|---|---|---|---|
|
Time to Event (Diagnosis of Mild Cognitive Impairment or Dementia, Due to Alzheimer's Disease (AD))
Week 26
|
1.00 proportion of participants
Interval 1.0 to 1.0
|
1.00 proportion of participants
Interval 1.0 to 1.0
|
0.98 proportion of participants
Interval 0.95 to 0.99
|
0.98 proportion of participants
Interval 0.94 to 0.99
|
|
Time to Event (Diagnosis of Mild Cognitive Impairment or Dementia, Due to Alzheimer's Disease (AD))
Week 52
|
1.00 proportion of participants
Interval 1.0 to 1.0
|
1.00 proportion of participants
Interval 1.0 to 1.0
|
0.93 proportion of participants
Interval 0.88 to 0.96
|
0.95 proportion of participants
Interval 0.9 to 0.98
|
|
Time to Event (Diagnosis of Mild Cognitive Impairment or Dementia, Due to Alzheimer's Disease (AD))
Week 78
|
0.97 proportion of participants
Interval 0.83 to 1.0
|
1.00 proportion of participants
Interval 1.0 to 1.0
|
0.88 proportion of participants
Interval 0.79 to 0.93
|
0.85 proportion of participants
Interval 0.63 to 0.94
|
|
Time to Event (Diagnosis of Mild Cognitive Impairment or Dementia, Due to Alzheimer's Disease (AD))
Week 104
|
0.97 proportion of participants
Interval 0.83 to 1.0
|
1.00 proportion of participants
Interval 1.0 to 1.0
|
0.88 proportion of participants
Interval 0.79 to 0.93
|
0.85 proportion of participants
Interval 0.63 to 0.94
|
PRIMARY outcome
Timeframe: CI = Baseline to Weeks 26, 52,78 104 and Baseline to last assessment; CII = Baseline to Weeks 26, 52, 78, 104 and Baseline to Last on-treatment and Baseline to Last off-treatmentPopulation: Only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
APCC is a composite score derived from the specific scores from the Repeatable Battery for the Assessment of Neurological Status (RBANS), Mini-Mental State Examination (MMSE) and the Raven's Progressive Matrices. The APCC score is a weighted score with ranges from from 0 to 100 where higher scores correspond to better cognitive performance.
Outcome measures
| Measure |
Cohort I (CI) CAD106
n=41 Participants
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort I (CI) CAD106 Placebo
n=23 Participants
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort II (CII) CNP520
n=179 Participants
CNP520 (50 mg) capsules taken once daily orally
|
Cohort II (CII) CNP520 Placebo
n=125 Participants
Placebo to CNP520 capsules taken once daily orally
|
|---|---|---|---|---|
|
Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score
Week 26
|
-1.1 Total scores
Standard Deviation 4.10
|
-2.0 Total scores
Standard Deviation 3.90
|
-3.3 Total scores
Standard Deviation 4.54
|
-1.0 Total scores
Standard Deviation 4.65
|
|
Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score
Week 52
|
0.9 Total scores
Standard Deviation 4.24
|
1.4 Total scores
Standard Deviation 3.36
|
0.3 Total scores
Standard Deviation 4.27
|
2.2 Total scores
Standard Deviation 6.11
|
|
Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score
Week 78
|
0.2 Total scores
Standard Deviation 4.15
|
-0.7 Total scores
Standard Deviation 5.48
|
-4.1 Total scores
Standard Deviation 4.14
|
2.4 Total scores
Standard Deviation 4.23
|
|
Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score
Week 104
|
-1.4 Total scores
Standard Deviation 4.67
|
0.3 Total scores
Standard Deviation 4.00
|
-6.7 Total scores
Standard Deviation 3.95
|
—
|
|
Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score
CI-Last post BL assessment
|
0.0 Total scores
Standard Deviation 4.62
|
0.1 Total scores
Standard Deviation 3.87
|
—
|
—
|
|
Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score
CII - Last on treatment
|
—
|
—
|
-1.7 Total scores
Standard Deviation 4.81
|
0.1 Total scores
Standard Deviation 4.58
|
|
Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score
CII-Last off treatment
|
—
|
—
|
-0.1 Total scores
Standard Deviation 4.72
|
0.2 Total scores
Standard Deviation 4.56
|
SECONDARY outcome
Timeframe: CI = Baseline to Weeks 26, 52,78 104 and Baseline to last assessment; CII = Baseline to Weeks 26, 52, 78, 104 and Baseline to Last on-treatment and Baseline to Last off-treatmentPopulation: Only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
The CDR was obtained through semi-structured interviews of participants and informants, and cognitive functioning was rated on a 5-point scale of functioning in six domains: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. The CDR global score ranged from zero to three, while the CDR-SOB was the sum of the ratings from the six domains, ranging from 0 to 18 with a minimum increment of 0.5. Higher scores indicated greater disease severity.
Outcome measures
| Measure |
Cohort I (CI) CAD106
n=41 Participants
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort I (CI) CAD106 Placebo
n=23 Participants
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort II (CII) CNP520
n=174 Participants
CNP520 (50 mg) capsules taken once daily orally
|
Cohort II (CII) CNP520 Placebo
n=122 Participants
Placebo to CNP520 capsules taken once daily orally
|
|---|---|---|---|---|
|
Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Score
Week 26
|
-0.04 Scores on a scale
Standard Deviation 0.234
|
0.00 Scores on a scale
Standard Deviation 0.000
|
0.04 Scores on a scale
Standard Deviation 0.361
|
0.00 Scores on a scale
Standard Deviation 0.336
|
|
Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Score
Week 52
|
-0.01 Scores on a scale
Standard Deviation 0.237
|
0.02 Scores on a scale
Standard Deviation 0.104
|
-0.02 Scores on a scale
Standard Deviation 0.281
|
-0.08 Scores on a scale
Standard Deviation 0.541
|
|
Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Score
Week 78
|
-0.04 Scores on a scale
Standard Deviation 0.237
|
0.03 Scores on a scale
Standard Deviation 0.118
|
0.14 Scores on a scale
Standard Deviation 0.802
|
-0.14 Scores on a scale
Standard Deviation 0.244
|
|
Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Score
Week 104
|
0.15 Scores on a scale
Standard Deviation 0.460
|
0.06 Scores on a scale
Standard Deviation 0.167
|
-0.17 Scores on a scale
Standard Deviation 0.764
|
—
|
|
Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Score
CI Last post baseline assessment
|
0.04 Scores on a scale
Standard Deviation 0.343
|
0.00 Scores on a scale
Standard Deviation 0.302
|
—
|
—
|
|
Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Score
CII Last on-treatment
|
—
|
—
|
0.06 Scores on a scale
Standard Deviation 0.505
|
0.03 Scores on a scale
Standard Deviation 0.410
|
|
Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Score
CII Last off-treatment
|
—
|
—
|
0.05 Scores on a scale
Standard Deviation 0.464
|
-0.01 Scores on a scale
Standard Deviation 0.519
|
SECONDARY outcome
Timeframe: CI = Baseline to Weeks 26, 52,78 104 and Baseline to last assessment; CII = Baseline to Weeks 26, 52, 78, 104 and Baseline to Last on-treatment and Baseline to Last off-treatmentPopulation: Only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Repeatable Battery for the Assessment of Neurological Status (RBANS) is a clinical tool designed to detect and characterize the earliest neurocognitive changes associated with dementia. The RBANS generates age-adjusted index scores for five neurocognitive domains: Immediate Memory, Visuospatial/Constructional, Language, Attention and Delayed Memory, which are used to calculate a Total Scale Index score. Index scores and total score range from 40 to 160 and a higher score indicates better cognitive functioning.
Outcome measures
| Measure |
Cohort I (CI) CAD106
n=41 Participants
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort I (CI) CAD106 Placebo
n=23 Participants
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort II (CII) CNP520
n=209 Participants
CNP520 (50 mg) capsules taken once daily orally
|
Cohort II (CII) CNP520 Placebo
n=141 Participants
Placebo to CNP520 capsules taken once daily orally
|
|---|---|---|---|---|
|
Change in the Total Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Total Week 26
|
-5.1 scores
Standard Deviation 7.25
|
-3.0 scores
Standard Deviation 7.51
|
-4.1 scores
Standard Deviation 8.58
|
-2.6 scores
Standard Deviation 7.83
|
|
Change in the Total Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Total Week 52
|
-1.2 scores
Standard Deviation 7.82
|
4.5 scores
Standard Deviation 7.10
|
-0.1 scores
Standard Deviation 7.91
|
1.4 scores
Standard Deviation 8.06
|
|
Change in the Total Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Total Week 78
|
-2.1 scores
Standard Deviation 7.69
|
-4.0 scores
Standard Deviation 7.82
|
-12.1 scores
Standard Deviation 7.40
|
-4.8 scores
Standard Deviation 5.99
|
|
Change in the Total Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Total Week 104
|
-1.4 scores
Standard Deviation 6.74
|
-3.0 scores
Standard Deviation 8.34
|
-7.7 scores
Standard Deviation 15.57
|
—
|
|
Change in the Total Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Total CI Last post baseline assessment
|
-1.0 scores
Standard Deviation 9.27
|
0.4 scores
Standard Deviation 7.20
|
—
|
—
|
|
Change in the Total Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Total CII Last on-treatment
|
—
|
—
|
-2.7 scores
Standard Deviation 8.65
|
-0.2 scores
Standard Deviation 9.22
|
|
Change in the Total Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Total CII Last off-treatment
|
—
|
—
|
-1.5 scores
Standard Deviation 9.20
|
-0.6 scores
Standard Deviation 8.83
|
SECONDARY outcome
Timeframe: CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatmentPopulation: Only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Repeatable Battery for the Assessment of Neurological Status (RBANS) is a clinical tool designed to detect and characterize the earliest neurocognitive changes associated with dementia. The RBANS generates age-adjusted index scores for five neurocognitive domains: Immediate Memory, Visuospatial/Constructional, Language, Attention and Delayed Memory, which are used to calculate a Total Scale Index score. Index scores and total score range from 40 to 160 and a higher score indicates better cognitive functioning.
Outcome measures
| Measure |
Cohort I (CI) CAD106
n=41 Participants
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort I (CI) CAD106 Placebo
n=23 Participants
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort II (CII) CNP520
n=209 Participants
CNP520 (50 mg) capsules taken once daily orally
|
Cohort II (CII) CNP520 Placebo
n=141 Participants
Placebo to CNP520 capsules taken once daily orally
|
|---|---|---|---|---|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
CII-Attention Last off-treatment
|
—
|
—
|
1.0 scores
Standard Deviation 1.64
|
1.2 scores
Standard Deviation 11.07
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Immediate memory - Week 26
|
-8.6 scores
Standard Deviation 10.68
|
-3.8 scores
Standard Deviation 11.16
|
-7.4 scores
Standard Deviation 13.11
|
-3.7 scores
Standard Deviation 12.15
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Immediate memory - Week 52
|
1.3 scores
Standard Deviation 10.81
|
4.8 scores
Standard Deviation 8.68
|
0.6 scores
Standard Deviation 13.55
|
5.1 scores
Standard Deviation 11.73
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
CI Immediate memory - Last post baseline assessment
|
-1.1 scores
Standard Deviation 13.11
|
1.1 scores
Standard Deviation 14.52
|
—
|
—
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
CII Immediate memory - Last on-treatment
|
—
|
—
|
-3.7 scores
Standard Deviation 14.43
|
0.6 scores
Standard Deviation 13.54
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
CII Immediate memory - Last off-treatment
|
—
|
—
|
-3.2 scores
Standard Deviation 13.76
|
-2.0 scores
Standard Deviation 11.90
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Visuospatial Week 26
|
-6.5 scores
Standard Deviation 15.21
|
0.7 scores
Standard Deviation 12.39
|
-3.5 scores
Standard Deviation 14.98
|
-2.4 scores
Standard Deviation 13.00
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Visuospatial Week 52
|
-6.5 scores
Standard Deviation 14.59
|
3.0 scores
Standard Deviation 15.09
|
-1.4 scores
Standard Deviation 14.29
|
-4.8 scores
Standard Deviation 12.60
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
CI Visuospatial Last post baseline assessment
|
-4.7 scores
Standard Deviation 13.91
|
1.9 scores
Standard Deviation 12.72
|
—
|
—
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
CII Visuospatial Last on-treatment n=
|
—
|
—
|
-3.5 scores
Standard Deviation 14.59
|
-2.6 scores
Standard Deviation 14.92
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
CII Visuospatial Last off-treatment
|
—
|
—
|
-1.2 scores
Standard Deviation 15.13
|
-0.8 scores
Standard Deviation 15.18
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Language Week 26
|
-1.4 scores
Standard Deviation 12.91
|
-2.8 scores
Standard Deviation 11.42
|
-0.1 scores
Standard Deviation 12.05
|
-1.5 scores
Standard Deviation 11.87
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Language Week 52
|
2.6 scores
Standard Deviation 10.29
|
2.0 scores
Standard Deviation 11.51
|
-0.3 scores
Standard Deviation 12.88
|
0.8 scores
Standard Deviation 9.72
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
CI Language Last post baseline assessment
|
1.9 scores
Standard Deviation 13.00
|
-4.5 scores
Standard Deviation 12.86
|
—
|
—
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
CII Language Last on-treatment
|
—
|
—
|
-0.1 scores
Standard Deviation 12.07
|
-0.1 scores
Standard Deviation 11.93
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
CII Language Last off-treatment
|
—
|
—
|
-1.0 scores
Standard Deviation 13.19
|
-1.8 scores
Standard Deviation 11.25
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Attention Week 26
|
1.8 scores
Standard Deviation 9.40
|
-0.6 scores
Standard Deviation 14.19
|
-0.7 scores
Standard Deviation 10.42
|
-0.6 scores
Standard Deviation 11.67
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Attention Week 52
|
0.9 scores
Standard Deviation 10.80
|
-0.5 scores
Standard Deviation 13.09
|
-0.2 scores
Standard Deviation 10.02
|
2.7 scores
Standard Deviation 10.77
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
CI Attention Last post baseline assessment
|
2.0 scores
Standard Deviation 12.91
|
2.0 scores
Standard Deviation 10.25
|
—
|
—
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
CII Attention Last on-treatment
|
—
|
—
|
0.1 scores
Standard Deviation 10.80
|
0.8 scores
Standard Deviation 11.20
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Delayed memory - Week 26
|
-3.8 scores
Standard Deviation 7.83
|
-2.7 scores
Standard Deviation 7.64
|
-3.8 scores
Standard Deviation 11.20
|
-2.6 scores
Standard Deviation 8.85
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Delayed memory - Week 52
|
-2.0 scores
Standard Deviation 8.01
|
3.2 scores
Standard Deviation 6.23
|
2.3 scores
Standard Deviation 9.09
|
0.6 scores
Standard Deviation 11.73
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
CI Delayed memory - Last post baseline assessment
|
-1.0 scores
Standard Deviation 10.20
|
1.3 scores
Standard Deviation 8.44
|
—
|
—
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
CII Delayed memory - Last on-treatment
|
—
|
—
|
-2.5 scores
Standard Deviation 10.61
|
0.4 scores
Standard Deviation 10.28
|
|
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
CII Delayed memory - Last off-treatment
|
—
|
—
|
-1.1 scores
Standard Deviation 10.75
|
1.1 scores
Standard Deviation 11.28
|
SECONDARY outcome
Timeframe: CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatmentPopulation: Only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Everyday Cognition Scale (ECog) measures cognitively-relevant everyday abilities comprised of 39 items covering 6 cognitively-relevant domains: Everyday Memory, Everyday Language, Everyday Visuospatial Abilities, Everyday Planning, Everyday Organization, and Everyday Divided Attention. The questionnaire is a self-reported measure completed by both participant and study partner (informant). The total score for the 39 items ranges from 39 to 195, with greater scores indicating worse daily function.
Outcome measures
| Measure |
Cohort I (CI) CAD106
n=40 Participants
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort I (CI) CAD106 Placebo
n=22 Participants
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort II (CII) CNP520
n=178 Participants
CNP520 (50 mg) capsules taken once daily orally
|
Cohort II (CII) CNP520 Placebo
n=119 Participants
Placebo to CNP520 capsules taken once daily orally
|
|---|---|---|---|---|
|
Change in the Everyday Cognition Scale (ECog-Subject) Total Scores
Week 26
|
-1.0 Total scores
Standard Deviation 2.94
|
2.3 Total scores
Standard Deviation 4.80
|
1.8 Total scores
Standard Deviation 6.03
|
0.6 Total scores
Standard Deviation 6.45
|
|
Change in the Everyday Cognition Scale (ECog-Subject) Total Scores
Week 52
|
0.6 Total scores
Standard Deviation 5.23
|
0.4 Total scores
Standard Deviation 2.99
|
2.7 Total scores
Standard Deviation 6.16
|
0.2 Total scores
Standard Deviation 5.01
|
|
Change in the Everyday Cognition Scale (ECog-Subject) Total Scores
CI Last post baseline assessment
|
0.6 Total scores
Standard Deviation 5.02
|
1.6 Total scores
Standard Deviation 4.07
|
—
|
—
|
|
Change in the Everyday Cognition Scale (ECog-Subject) Total Scores
CII Last on-treatment
|
—
|
—
|
2.6 Total scores
Standard Deviation 7.81
|
0.9 Total scores
Standard Deviation 6.48
|
|
Change in the Everyday Cognition Scale (ECog-Subject) Total Scores
CII Last off-treatment
|
—
|
—
|
1.6 Total scores
Standard Deviation 6.77
|
0.8 Total scores
Standard Deviation 6.13
|
SECONDARY outcome
Timeframe: CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatmentPopulation: Only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Everyday Cognition Scale (ECog) measures cognitively-relevant everyday abilities comprised of 39 items covering 6 cognitively-relevant domains: Everyday Memory, Everyday Language, Everyday Visuospatial Abilities, Everyday Planning, Everyday Organization, and Everyday Divided Attention. The questionnaire is a self-reported measure completed by both participant and study partner (informant). The total score for the 39 items ranges from 39 to 195, with greater scores indicating worse daily function. Cohort I=C I and Cohort II=C II.
Outcome measures
| Measure |
Cohort I (CI) CAD106
n=37 Participants
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort I (CI) CAD106 Placebo
n=23 Participants
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort II (CII) CNP520
n=160 Participants
CNP520 (50 mg) capsules taken once daily orally
|
Cohort II (CII) CNP520 Placebo
n=113 Participants
Placebo to CNP520 capsules taken once daily orally
|
|---|---|---|---|---|
|
Change in the Everyday Cognition Scale (ECog-Informant) Total Scores
Week 26
|
-0.4 Total scores
Standard Deviation 4.21
|
-1.0 Total scores
Standard Deviation 4.87
|
0.1 Total scores
Standard Deviation 6.84
|
-0.7 Total scores
Standard Deviation 8.69
|
|
Change in the Everyday Cognition Scale (ECog-Informant) Total Scores
Week 52
|
-0.2 Total scores
Standard Deviation 3.15
|
-0.3 Total scores
Standard Deviation 5.12
|
1.4 Total scores
Standard Deviation 5.18
|
-0.2 Total scores
Standard Deviation 9.59
|
|
Change in the Everyday Cognition Scale (ECog-Informant) Total Scores
CI Last post baseline assessment
|
-1.1 Total scores
Standard Deviation 4.23
|
-1.0 Total scores
Standard Deviation 4.88
|
—
|
—
|
|
Change in the Everyday Cognition Scale (ECog-Informant) Total Scores
CII Last on-treatment
|
—
|
—
|
1.3 Total scores
Standard Deviation 8.76
|
0.1 Total scores
Standard Deviation 9.12
|
|
Change in the Everyday Cognition Scale (ECog-Informant) Total Scores
CII Last off-treatment
|
—
|
—
|
1.4 Total scores
Standard Deviation 8.49
|
-0.5 Total scores
Standard Deviation 10.10
|
SECONDARY outcome
Timeframe: Baseline to end of exposure for a maximum of 1455 days for CI and 907 days for CIIPopulation: Safety analysis set - only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Safety MRI included sequences necessary for ascertainment of possible ARIA-E (Amyloid Related Imaging Abnormality-Edema), ARIA-H (Amyloid Related Imaging Abnormality- Hemorrhage, including superficial siderosis and microhemorrhages), assessment of recent infarcts and white matter integrity examination (White matter disease worsening since baseline) and a general assessment of brain abnormalities. Assessment of cerebral amyloid angiopathy (CAA) is included in the overall safety MRI findings results.
Outcome measures
| Measure |
Cohort I (CI) CAD106
n=42 Participants
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort I (CI) CAD106 Placebo
n=23 Participants
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort II (CII) CNP520
n=249 Participants
CNP520 (50 mg) capsules taken once daily orally
|
Cohort II (CII) CNP520 Placebo
n=163 Participants
Placebo to CNP520 capsules taken once daily orally
|
|---|---|---|---|---|
|
Number of Participants With Newly Occurring Safety MRI Abnormalities (ARIA-E, ARIA-H,White Matter Disease and Any Other MRI Abnormalities)
Questionable presence of ARIA-E
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Newly Occurring Safety MRI Abnormalities (ARIA-E, ARIA-H,White Matter Disease and Any Other MRI Abnormalities)
Presence of ARIA-E
|
1 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Newly Occurring Safety MRI Abnormalities (ARIA-E, ARIA-H,White Matter Disease and Any Other MRI Abnormalities)
ARIA-E - If present, the worst Severity=moderate
|
1 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Newly Occurring Safety MRI Abnormalities (ARIA-E, ARIA-H,White Matter Disease and Any Other MRI Abnormalities)
Presence of ARIA-H - >4 microhemorrhages (new hemosiderin deposits < 10 mm)
|
2 Participants
|
0 Participants
|
6 Participants
|
2 Participants
|
|
Number of Participants With Newly Occurring Safety MRI Abnormalities (ARIA-E, ARIA-H,White Matter Disease and Any Other MRI Abnormalities)
White matter disease worsening: 1-3 increase
|
0 Participants
|
2 Participants
|
6 Participants
|
1 Participants
|
|
Number of Participants With Newly Occurring Safety MRI Abnormalities (ARIA-E, ARIA-H,White Matter Disease and Any Other MRI Abnormalities)
White matter disease worsening: 4 - 8 increase
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Newly Occurring Safety MRI Abnormalities (ARIA-E, ARIA-H,White Matter Disease and Any Other MRI Abnormalities)
White matter disease worsening > 8 increase
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Newly Occurring Safety MRI Abnormalities (ARIA-E, ARIA-H,White Matter Disease and Any Other MRI Abnormalities)
Any other MRI abnormalities
|
2 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatmentPopulation: Safety analysis set - only participants with a value at both Baseline and that visit are included. For CI: last post-baseline assessment collected during the study. For CII: Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Annualized % change from baseline in volume of specific brain regions of interest (ROIs): whole brain (WB), hippocampus (Hip), and lateral ventricles (LV). Annualized percentage change was calculated as (percentage per participant / time interval (in days)) x 365.25. Time interval (in days) was derived as date of current MRI assessment on study drug - date of baseline MRI assessment + 1.
Outcome measures
| Measure |
Cohort I (CI) CAD106
n=42 Participants
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort I (CI) CAD106 Placebo
n=23 Participants
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort II (CII) CNP520
n=201 Participants
CNP520 (50 mg) capsules taken once daily orally
|
Cohort II (CII) CNP520 Placebo
n=135 Participants
Placebo to CNP520 capsules taken once daily orally
|
|---|---|---|---|---|
|
Annualized Percent Change on Volume of Brain Regions
WB Week 26
|
-0.7570 Percentage of volume change
Standard Deviation 1.33114
|
-0.6044 Percentage of volume change
Standard Deviation 1.29608
|
-0.9318 Percentage of volume change
Standard Deviation 1.06843
|
-0.4616 Percentage of volume change
Standard Deviation 1.00537
|
|
Annualized Percent Change on Volume of Brain Regions
WB Week 52
|
-0.5144 Percentage of volume change
Standard Deviation 0.66578
|
-0.3395 Percentage of volume change
Standard Deviation 0.75810
|
-0.6590 Percentage of volume change
Standard Deviation 0.64838
|
-0.4227 Percentage of volume change
Standard Deviation 0.58778
|
|
Annualized Percent Change on Volume of Brain Regions
WB CI Last post baseline assessment
|
-0.4645 Percentage of volume change
Standard Deviation 0.57503
|
-0.5321 Percentage of volume change
Standard Deviation 0.46526
|
—
|
—
|
|
Annualized Percent Change on Volume of Brain Regions
WB CII Last on-treatment
|
—
|
—
|
-0.8268 Percentage of volume change
Standard Deviation 0.94889
|
-0.5181 Percentage of volume change
Standard Deviation 0.92086
|
|
Annualized Percent Change on Volume of Brain Regions
WB CII Last off-treatment
|
—
|
—
|
-0.6748 Percentage of volume change
Standard Deviation 0.62542
|
-0.3317 Percentage of volume change
Standard Deviation 0.62616
|
|
Annualized Percent Change on Volume of Brain Regions
Hip Week 26
|
-1.3262 Percentage of volume change
Standard Deviation 2.35453
|
-0.9245 Percentage of volume change
Standard Deviation 2.81731
|
-1.6603 Percentage of volume change
Standard Deviation 2.65529
|
-0.8817 Percentage of volume change
Standard Deviation 2.06227
|
|
Annualized Percent Change on Volume of Brain Regions
Hip Week 52
|
-1.0376 Percentage of volume change
Standard Deviation 1.44310
|
-0.7780 Percentage of volume change
Standard Deviation 1.81604
|
-1.2438 Percentage of volume change
Standard Deviation 1.79988
|
-0.9567 Percentage of volume change
Standard Deviation 1.42941
|
|
Annualized Percent Change on Volume of Brain Regions
Hip CI Last post baseline assessment
|
-1.0801 Percentage of volume change
Standard Deviation 1.38061
|
-1.0477 Percentage of volume change
Standard Deviation 1.33603
|
—
|
—
|
|
Annualized Percent Change on Volume of Brain Regions
Hip CII Last on-treatment
|
—
|
—
|
-1.4790 Percentage of volume change
Standard Deviation 2.36526
|
-0.9984 Percentage of volume change
Standard Deviation 1.85655
|
|
Annualized Percent Change on Volume of Brain Regions
Hip CII Last off-treatment
|
—
|
—
|
-1.9375 Percentage of volume change
Standard Deviation 2.03593
|
-1.0498 Percentage of volume change
Standard Deviation 1.66596
|
|
Annualized Percent Change on Volume of Brain Regions
LV Week 26
|
4.1848 Percentage of volume change
Standard Deviation 5.77286
|
2.5581 Percentage of volume change
Standard Deviation 7.54667
|
4.5176 Percentage of volume change
Standard Deviation 5.59748
|
3.9735 Percentage of volume change
Standard Deviation 4.23237
|
|
Annualized Percent Change on Volume of Brain Regions
LV Week 52
|
4.2060 Percentage of volume change
Standard Deviation 3.92877
|
2.8232 Percentage of volume change
Standard Deviation 5.04358
|
3.3854 Percentage of volume change
Standard Deviation 3.71214
|
2.9059 Percentage of volume change
Standard Deviation 3.18734
|
|
Annualized Percent Change on Volume of Brain Regions
LV CI Last post baseline assessment
|
4.0543 Percentage of volume change
Standard Deviation 3.75310
|
3.5427 Percentage of volume change
Standard Deviation 3.53772
|
—
|
—
|
|
Annualized Percent Change on Volume of Brain Regions
LV CII Last on-treatment
|
—
|
—
|
4.3588 Percentage of volume change
Standard Deviation 5.07839
|
4.0308 Percentage of volume change
Standard Deviation 3.64102
|
|
Annualized Percent Change on Volume of Brain Regions
LV CII Last off-treatment
|
—
|
—
|
3.9617 Percentage of volume change
Standard Deviation 2.61831
|
2.6052 Percentage of volume change
Standard Deviation 3.54903
|
SECONDARY outcome
Timeframe: Baseline to last assessmentPopulation: No lumbar punctures for CSF collection were performed due to early termination of trial
Alzheimer's Disease-related biomarkers analyzed in cerebrospinal fluid (CSF): Amyloid Beta 40 (Aβ40)
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to last assessmentPopulation: No lumbar punctures for CSF collection were performed due to early termination of trial
Alzheimer's Disease-related biomarkers analyzed in cerebrospinal fluid (CSF): Amyloid Beta 42 (Aβ42)
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to last assessmentPopulation: No lumbar punctures for CSF collection were performed due to early termination of trial
Alzheimer's Disease-related biomarkers analyzed in cerebrospinal fluid (CSF): total tau protein and phosphorylated tau protein levels
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to last assessmentPopulation: No post baseline data collected
To demonstrate the effects of CNP520 vs placebo on tau pathology in the brain
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline up to approximately Week 104Population: Only available for Cohort I. For Cohort II, no post-baseline (year 2) amyloid PET scans could be obtained due to the early trial termination
To demonstrate the effects of CAD106 vs placebo on Alzheimer's Disease-related biomarkers
Outcome measures
| Measure |
Cohort I (CI) CAD106
n=42 Participants
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort I (CI) CAD106 Placebo
n=23 Participants
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort II (CII) CNP520
CNP520 (50 mg) capsules taken once daily orally
|
Cohort II (CII) CNP520 Placebo
Placebo to CNP520 capsules taken once daily orally
|
|---|---|---|---|---|
|
Cohort I : Annualized Change in Amyloid Deposition as Measured by Centiloids of Positron Emission Tomography (PET) Scan With Amyloid Radiotracer
|
-0.911 Centiloids
Standard Deviation 5.6596
|
8.367 Centiloids
Standard Deviation 6.6805
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to Week 26 and week 52, CI baseline to last assessment. CII baseline to last on-treatment and to last off-treatmentPopulation: Only participants with a value at both Baseline and that visit are included. CI last post-baseline assessment. CII Last on-treatment is the last assessment before or at last day on study drug + 31 days.
Alzheimer's Disease-related biomarkers analyzed in blood serum: light chain neurofilaments (NfL)
Outcome measures
| Measure |
Cohort I (CI) CAD106
n=20 Participants
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort I (CI) CAD106 Placebo
n=10 Participants
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort II (CII) CNP520
n=72 Participants
CNP520 (50 mg) capsules taken once daily orally
|
Cohort II (CII) CNP520 Placebo
n=53 Participants
Placebo to CNP520 capsules taken once daily orally
|
|---|---|---|---|---|
|
Change in Serum Neurofilaments
Week 26
|
1.44 pg/mL
Standard Deviation 3.165
|
-3.89 pg/mL
Standard Deviation 13.058
|
0.644 pg/mL
Standard Deviation 3.4879
|
0.362 pg/mL
Standard Deviation 6.7547
|
|
Change in Serum Neurofilaments
Week 52
|
2.63 pg/mL
Standard Deviation 5.716
|
-6.09 pg/mL
Standard Deviation 16.542
|
1.921 pg/mL
Standard Deviation 4.0515
|
-4.852 pg/mL
Standard Deviation 14.2270
|
|
Change in Serum Neurofilaments
C I Last post baseline assessment
|
1.77 pg/mL
Standard Deviation 4.643
|
-3.31 pg/mL
Standard Deviation 12.858
|
—
|
—
|
|
Change in Serum Neurofilaments
C II Last on-treatment
|
—
|
—
|
0.647 pg/mL
Standard Deviation 3.5357
|
0.280 pg/mL
Standard Deviation 6.8289
|
|
Change in Serum Neurofilaments
C II Last off-treatment
|
—
|
—
|
-0.004 pg/mL
Standard Deviation 3.7102
|
-2.145 pg/mL
Standard Deviation 2.6799
|
SECONDARY outcome
Timeframe: Baseline to end of exposure for a maximum of 1455 days for CI and 907 days for CIIPopulation: Safety analysis set which includes only participants with events
Prospective suicidality assessment was performed with the use of Columbia-Suicide Severity Rating Scale (C-SSRS), a questionnaire using a detailed branched logic algorithm evaluating participant's suicidality ideation and behavior. Answer "yes" on item 4 or 5 of the Suicidal Ideation section or "yes" on any item of the Suicidal Behavior section was considered positive.
Outcome measures
| Measure |
Cohort I (CI) CAD106
n=42 Participants
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort I (CI) CAD106 Placebo
n=23 Participants
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort II (CII) CNP520
n=249 Participants
CNP520 (50 mg) capsules taken once daily orally
|
Cohort II (CII) CNP520 Placebo
n=163 Participants
Placebo to CNP520 capsules taken once daily orally
|
|---|---|---|---|---|
|
Number of Suicidal Ideation or Behavior Events
Any suicidal ideation
|
2 events
|
1 events
|
12 events
|
4 events
|
|
Number of Suicidal Ideation or Behavior Events
Any suicidal behavior
|
0 events
|
0 events
|
1 events
|
1 events
|
SECONDARY outcome
Timeframe: Month 6 to Month 60Population: No analysis performed due to early termination, no month 60 data
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 9, 13, 15, 26 and quarterly thereafter (trough values)Population: Safety population
Cmax is the maximum Titer Concentration of any post-baseline 'on treatment' visit. A visit is considered as 'on treatment' if visit date is within {last injection + 180 days}. \- Geometric mean and CI's are back-transformed from the estimates for Log mean and CI's.
Outcome measures
| Measure |
Cohort I (CI) CAD106
n=41 Participants
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort I (CI) CAD106 Placebo
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort II (CII) CNP520
CNP520 (50 mg) capsules taken once daily orally
|
Cohort II (CII) CNP520 Placebo
Placebo to CNP520 capsules taken once daily orally
|
|---|---|---|---|---|
|
Cohort I: Peak Concentration (Cmax) of CAD106 Induced Abeta-specific Antibody Titers
|
128.76 Days x titer levels rel. to ref. serum
Interval 99.05 to 167.37
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 9, 13, 15, 26 and quarterly thereafter (trough values)Population: Safety population
AUC is calculated based on 'on treatment' visit only.(missing values for peak visits were linearly interpolated for calculation; missing values for trough visits were imputed by average of non-missing trough values.).
Outcome measures
| Measure |
Cohort I (CI) CAD106
n=42 Participants
CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort I (CI) CAD106 Placebo
Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter
|
Cohort II (CII) CNP520
CNP520 (50 mg) capsules taken once daily orally
|
Cohort II (CII) CNP520 Placebo
Placebo to CNP520 capsules taken once daily orally
|
|---|---|---|---|---|
|
Cohort I: Area Under the Concentration Curve (AUC) of CAD106 Induced Abeta-specific Antibody Titers
|
34999.89 Days x titer levels rel. to ref. serum
Interval 22992.17 to 53278.68
|
—
|
—
|
—
|
Adverse Events
Cohort I @CAD106
Serious events: 4 serious events
Other events: 36 other events
Deaths: 0 deaths
Cohort I @Placebo
Serious events: 3 serious events
Other events: 21 other events
Deaths: 0 deaths
Cohort II (CNP520 50)
Serious events: 8 serious events
Other events: 106 other events
Deaths: 0 deaths
Cohort II Placebo
Serious events: 7 serious events
Other events: 76 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cohort I @CAD106
n=42 participants at risk
Cohort I @CAD106
|
Cohort I @Placebo
n=23 participants at risk
Cohort I @Placebo
|
Cohort II (CNP520 50)
n=249 participants at risk
CNP520 (50 mg) capsules taken once daily orally
|
Cohort II Placebo
n=163 participants at risk
Cohort II @Placebo
|
|---|---|---|---|---|
|
Cardiac disorders
Atrial flutter
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Cardiac disorders
Stress cardiomyopathy
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Gastrointestinal disorders
Nausea
|
2.4%
1/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
General disorders
Asthenia
|
2.4%
1/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
General disorders
Feeling jittery
|
2.4%
1/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
General disorders
Non-cardiac chest pain
|
2.4%
1/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Infections and infestations
Abscess limb
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Infections and infestations
Cellulitis
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Injury, poisoning and procedural complications
Animal bite
|
2.4%
1/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma in situ
|
2.4%
1/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Nervous system disorders
Cerebellar haemorrhage
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Nervous system disorders
Syncope
|
2.4%
1/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary mass
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
2.4%
1/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
Other adverse events
| Measure |
Cohort I @CAD106
n=42 participants at risk
Cohort I @CAD106
|
Cohort I @Placebo
n=23 participants at risk
Cohort I @Placebo
|
Cohort II (CNP520 50)
n=249 participants at risk
CNP520 (50 mg) capsules taken once daily orally
|
Cohort II Placebo
n=163 participants at risk
Cohort II @Placebo
|
|---|---|---|---|---|
|
Infections and infestations
Cellulitis
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Infections and infestations
Conjunctivitis bacterial
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Infections and infestations
Dacryocanaliculitis
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Infections and infestations
Influenza
|
2.4%
1/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
8.7%
2/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
1.2%
3/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
8.7%
2/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Cardiac disorders
Atrial flutter
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Cardiac disorders
Palpitations
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Congenital, familial and genetic disorders
Type V hyperlipidaemia
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Ear and labyrinth disorders
Deafness bilateral
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Ear and labyrinth disorders
Tinnitus
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
1.2%
3/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Endocrine disorders
Hypothyroidism
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Endocrine disorders
Thyroid mass
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Eye disorders
Glaucoma
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Eye disorders
Vitreous detachment
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
8.7%
2/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Gastrointestinal disorders
Constipation
|
7.1%
3/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
2.8%
7/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
1.2%
2/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Gastrointestinal disorders
Diarrhoea
|
7.1%
3/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
2.4%
6/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
1.8%
3/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Gastrointestinal disorders
Eosinophilic oesophagitis
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Gastrointestinal disorders
Nausea
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
2.0%
5/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
2.5%
4/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Gastrointestinal disorders
Pancreatic cyst
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Gastrointestinal disorders
Salivary gland disorder
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
General disorders
Chills
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
General disorders
Fatigue
|
26.2%
11/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
1.2%
3/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
General disorders
Influenza like illness
|
11.9%
5/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
General disorders
Injection site erythema
|
2.4%
1/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
General disorders
Injection site pain
|
23.8%
10/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
General disorders
Injection site pruritus
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
General disorders
Injection site reaction
|
9.5%
4/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
General disorders
Malaise
|
7.1%
3/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
General disorders
Oedema peripheral
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
General disorders
Pyrexia
|
16.7%
7/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
1.6%
4/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Immune system disorders
Seasonal allergy
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Infections and infestations
Acute sinusitis
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
8.7%
2/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Infections and infestations
Bronchitis
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.9%
8/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Infections and infestations
Nasopharyngitis
|
9.5%
4/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
8.7%
2/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.0%
10/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
1.2%
2/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Infections and infestations
Pharyngitis
|
2.4%
1/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Infections and infestations
Respiratory tract infection
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Infections and infestations
Sinusitis
|
7.1%
3/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
2.0%
5/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.9%
8/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Infections and infestations
Upper respiratory tract infection
|
16.7%
7/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
13.0%
3/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.4%
11/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
6.7%
11/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
8.7%
2/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
2.0%
5/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
2.5%
4/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.80%
2/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
2.5%
4/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Injury, poisoning and procedural complications
Contusion
|
7.1%
3/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
1.8%
3/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Injury, poisoning and procedural complications
Fall
|
9.5%
4/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
3.2%
8/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
2.5%
4/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Injury, poisoning and procedural complications
Injection related reaction
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Injury, poisoning and procedural complications
Mallet finger
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Injury, poisoning and procedural complications
Meniscus injury
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Investigations
C-reactive protein increased
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Investigations
Lumbar puncture
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Investigations
Urine albumin/creatinine ratio increased
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
3.6%
9/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
1.2%
2/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Investigations
Weight decreased
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
2.8%
7/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Investigations
Weight increased
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Metabolism and nutrition disorders
Vitamin B12 deficiency
|
2.4%
1/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
8.7%
2/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
1.6%
4/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
9.5%
4/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
2.4%
6/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
7/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.5%
4/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
2.8%
7/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
3.7%
6/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Musculoskeletal and connective tissue disorders
Exostosis
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Musculoskeletal and connective tissue disorders
Foot deformity
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
2.0%
5/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
1.8%
3/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
7.1%
3/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
13.0%
3/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
1.2%
3/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
9.5%
4/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
8.7%
2/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
2.4%
6/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
3.1%
5/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
1.2%
2/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of thyroid gland
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma of liver
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
|
2.4%
1/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Nervous system disorders
Ageusia
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Nervous system disorders
Carpal tunnel syndrome
|
2.4%
1/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Nervous system disorders
Cerebral cyst
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Nervous system disorders
Cervical radiculopathy
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Nervous system disorders
Dizziness
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
2.8%
7/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.61%
1/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Nervous system disorders
Headache
|
16.7%
7/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
2.4%
6/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
5.5%
9/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Nervous system disorders
Lethargy
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.80%
2/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Nervous system disorders
Paraesthesia
|
2.4%
1/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.80%
2/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Nervous system disorders
Presyncope
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Nervous system disorders
Radiculopathy
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Psychiatric disorders
Abnormal dreams
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
7.6%
19/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
3.1%
5/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.4%
11/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Psychiatric disorders
Insomnia
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
1.6%
4/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
5.5%
9/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Psychiatric disorders
Irritability
|
2.4%
1/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.80%
2/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Renal and urinary disorders
Cystitis haemorrhagic
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Renal and urinary disorders
Dysuria
|
2.4%
1/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Renal and urinary disorders
Hypercalciuria
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.1%
3/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
2.0%
5/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
1.2%
2/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
1.6%
4/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
2.4%
1/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
4.8%
2/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.40%
1/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
1.2%
2/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.0%
10/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
3.1%
5/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
|
Vascular disorders
Essential hypertension
|
0.00%
0/42 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
4.3%
1/23 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/249 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
0.00%
0/163 • Adverse events were reported from first dose of study treatment plus 31 days of washout period for a maximum duration of 1455 days for CI and 907 days for CII
|
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.
- Publication restrictions are in place
Restriction type: OTHER