The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase 2 Study of BIIB092 in Participants With Early Alzheimer's Disease (TANGO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03352557
Recruitment Status : Terminated (The study (NCT03352557) was terminated based on lack of efficacy following the placebo-controlled period readout.)
First Posted : November 24, 2017
Results First Posted : November 8, 2022
Last Update Posted : November 8, 2022
Sponsor:
Information provided by (Responsible Party):
Biogen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Alzheimer's Disease
Interventions Drug: BIIB092
Drug: Placebo
Enrollment 654
Recruitment Details Participants were enrolled at approximately 100 investigational sites from 03 May 2018 to 30 August 2021.
Pre-assignment Details A total of 654 participants with Alzheimer's Disease (AD) were enrolled and randomized to receive placebo or BIIB092 125/375/600/2000 milligrams(mg) in Placebo-Controlled (PC) period. Following PC period, 521 participants entered and 516 were dosed in Long-term Extension (LTE) period, and no participants completed the study due to early termination of the study. WBP/G=Withdrawal by Parent/Guardian
Arm/Group Title PC Period: Placebo PC Period: BIIB092 125 mg/4 Week PC Period: BIIB092 375 mg/12 Week PC Period: BIIB092 600 mg/4 Week PC Period: BIIB092 2000 mg/4 Week LTE Period: BIIB092 125 mg/4 Week LTE Period: BIIB092 375 mg/12 Week LTE Period: BIIB092 600 mg/4 Week LTE Period: BIIB092 2000 mg/4 Week - Early Start LTE Period: BIIB092 2000 mg/4 Week - Late Start
Hide Arm/Group Description Participants received BIIB092-matching placebo, intravenous (IV) infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period. Participants received BIIB092, 125 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period. Participants received BIIB092, 375 mg, IV infusion, on Day 1 and then once every 12 weeks for 76 weeks during the PC period. Participants received BIIB092, 600 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period. Participants received BIIB092, 2000 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period. Participants who received BIIB092, 125 mg, IV infusion during the PC period, continued to receive BIIB092, 125 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period. Participants who received BIIB092, 375 mg, IV infusion during the PC period, continued to receive BIIB092, 375 mg, IV infusion once every 12 weeks from Week 80 to Week 155 during the LTE period. Participants who received BIIB092, 600 mg, IV infusion during the PC period, continued to receive BIIB092, 600 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period. Participants who received BIIB092, 2000 mg, IV infusion during the PC period, continued to receive BIIB092, 2000 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period. Participants who received BIIB092-matching placebo, IV infusion during the PC period, received BIIB092, 2000 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period.
Period Title: PC Period: Day 1 to Week 78
Started 214 58 58 106 218 0 0 0 0 0
Safety Analysis Set [1] 214 58 58 106 214 0 0 0 0 0
Full Analysis Set (FAS) 214 58 58 106 214 0 0 0 0 0
Antidrug Antibody (ADA) Evaluable Set 211 57 57 105 212 0 0 0 0 0
Completed 172 48 50 91 175 0 0 0 0 0
Not Completed 42 10 8 15 43 0 0 0 0 0
Reason Not Completed
Death             1             1             0             0             1             0             0             0             0             0
Adverse Event             10             1             1             0             5             0             0             0             0             0
Progressive Disease             0             0             0             0             1             0             0             0             0             0
Noncompliance with Study Drug             1             0             0             0             0             0             0             0             0             0
Protocol Deviation             1             0             0             1             2             0             0             0             0             0
Randomized by Mistake             2             0             0             1             0             0             0             0             0             0
Site Terminated by Sponsor             2             1             1             1             2             0             0             0             0             0
Withdrawal by Participant-Study Visit Burden/Scheduling Conflicts             7             1             1             0             5             0             0             0             0             0
Withdrawal by Participant-Concern About Study Procedures/Perceived Risks             1             0             0             1             2             0             0             0             0             0
Withdrawal by Participant-Relocation (Moving or Has Moved)             1             1             0             1             1             0             0             0             0             0
Withdrawal by Participant-Desire for Change in Treatment (Unrelated to Safety)             0             0             1             0             1             0             0             0             0             0
Withdrawal by Participant-Other             6             2             2             5             7             0             0             0             0             0
WBP/G-Study Visit Burden/Scheduling Conflicts             0             0             0             1             3             0             0             0             0             0
WBP/G-Concern About Study Procedures/Perceived Risks             1             0             1             1             1             0             0             0             0             0
WBP/G-Desire for Change in Treatment (Unrelated to Safety)             1             0             0             0             1             0             0             0             0             0
WBP/G-Unable to Continue to Enable Participation due to Illness/Hospitalization/Death             0             0             0             0             1             0             0             0             0             0
WBP/G-Other             0             2             0             0             3             0             0             0             0             0
Physician Decision-Unrelated to Safety             2             0             0             0             1             0             0             0             0             0
Lost to Follow-up             1             0             1             0             2             0             0             0             0             0
Other             5             1             0             3             0             0             0             0             0             0
Not Dosed             0             0             0             0             4             0             0             0             0             0
[1]
Safety Analysis Set = Dosed Participants
Period Title: LTE Period: Week 80 to Week 173
Started 0 0 0 0 0 46 [1] 49 [2] 90 [2] 169 [3] 167 [4]
Safety Analysis Set [5] 0 0 0 0 0 45 49 89 168 165
Completed 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 46 49 90 169 167
Reason Not Completed
Death             0             0             0             0             0             1             0             1             1             1
Adverse Event             0             0             0             0             0             3             0             0             0             0
Site Terminated by Sponsor             0             0             0             0             0             0             0             0             2             0
Study Terminated by Sponsor             0             0             0             0             0             38             49             75             151             154
Withdrawal by Participant-Study Visit Burden/Scheduling Conflicts             0             0             0             0             0             1             0             5             3             3
Withdrawal by Participant-Relocation (Moving or Has Moved)             0             0             0             0             0             1             0             1             1             0
Withdrawal by Participant-Other             0             0             0             0             0             1             0             1             1             4
WBP/G-Study Visit Burden/Scheduling Conflicts             0             0             0             0             0             0             0             0             2             1
WBP/G-Concern About Study Procedures/Perceived Risks             0             0             0             0             0             0             0             1             0             0
WBP/G-Relocation (Moving or Has Moved)             0             0             0             0             0             0             0             2             0             0
WBP/G-Unable to Continue to Enable Participation due to Illness/Hospitalization/Death             0             0             0             0             0             0             0             2             1             0
WBP/G-Other             0             0             0             0             0             1             0             0             2             0
Physician Decision             0             0             0             0             0             0             0             0             0             3
Lost to Follow-up             0             0             0             0             0             0             0             0             3             1
Progressive Disease             0             0             0             0             0             0             0             1             2             0
Other             0             0             0             0             0             0             0             1             0             0
[1]
2 PC completers did not enter LTE.
[2]
1 PC completer did not enter LTE.
[3]
6 PC completers did not enter LTE.
[4]
5 PC completers did not enter LTE.
[5]
Safety Analysis Set = Dosed Participants
Arm/Group Title PC Period: Placebo PC Period: BIIB092 125 mg/4 Week PC Period: BIIB092 375 mg/12 Week PC Period: BIIB092 600 mg/4 Week PC Period: BIIB092 2000 mg/4 Week Total
Hide Arm/Group Description Participants received BIIB092-matching placebo, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period. Participants received BIIB092, 125 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period. Participants received BIIB092, 375 mg, IV infusion, on Day 1 and then once every 12 weeks for 76 weeks during the PC period. Participants received BIIB092, 600 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period. Participants received BIIB092, 2000 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period. Total of all reporting groups
Overall Number of Baseline Participants 214 58 58 106 218 654
Hide Baseline Analysis Population Description
Randomized participants included enrolled participants who received a randomization treatment assignment from the Interactive Response Technology (BIIB092 or placebo).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 214 participants 58 participants 58 participants 106 participants 218 participants 654 participants
69.8  (6.63) 70.4  (6.80) 70.3  (6.79) 69.7  (6.66) 69.4  (7.11) 69.7  (6.81)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 214 participants 58 participants 58 participants 106 participants 218 participants 654 participants
Female
106
  49.5%
28
  48.3%
26
  44.8%
55
  51.9%
114
  52.3%
329
  50.3%
Male
108
  50.5%
30
  51.7%
32
  55.2%
51
  48.1%
104
  47.7%
325
  49.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 214 participants 58 participants 58 participants 106 participants 218 participants 654 participants
Hispanic or Latino
3
   1.4%
2
   3.4%
2
   3.4%
1
   0.9%
9
   4.1%
17
   2.6%
Not Hispanic or Latino
208
  97.2%
53
  91.4%
55
  94.8%
103
  97.2%
208
  95.4%
627
  95.9%
Unknown or Not Reported
3
   1.4%
3
   5.2%
1
   1.7%
2
   1.9%
1
   0.5%
10
   1.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 214 participants 58 participants 58 participants 106 participants 218 participants 654 participants
American Indian or Alaska Native
1
   0.5%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.2%
Asian
5
   2.3%
3
   5.2%
2
   3.4%
6
   5.7%
7
   3.2%
23
   3.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
4
   1.9%
0
   0.0%
1
   1.7%
1
   0.9%
1
   0.5%
7
   1.1%
White
201
  93.9%
53
  91.4%
53
  91.4%
98
  92.5%
206
  94.5%
611
  93.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
3
   1.4%
2
   3.4%
2
   3.4%
1
   0.9%
4
   1.8%
12
   1.8%
1.Primary Outcome
Title PC Period: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description AE is any untoward medical occurrence in participant or clinical investigation participant administered pharmaceutical product and that does not necessarily have causal relationship with this treatment. AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of medicinal (investigational) product, whether or not related to medicinal (investigational) product. SAE is any untoward medical occurrence that at any dose, results in death; in view of investigator places participant at immediate risk of death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in congenital anomaly/birth defect; is medically important event. Participants who completed treatment period in PC period and did not enter LTE period were to be assessed at Week 90 (14 weeks after end of treatment) as safety follow-up.
Time Frame Day 1 to Week 78 (participants who entered LTE period); Day 1 up to Week 90 (participants who did not LTE period)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all randomized participants who received at least one dose of study treatment (BIIB092 or placebo).
Arm/Group Title PC Period: Placebo PC Period: BIIB092 125 mg/4 Week PC Period: BIIB092 375 mg/12 Week PC Period: BIIB092 600 mg/4 Week PC Period: BIIB092 2000 mg/4 Week
Hide Arm/Group Description:
Participants received BIIB092-matching placebo, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.
Participants received BIIB092, 125 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.
Participants received BIIB092, 375 mg, IV infusion, on Day 1 and then once every 12 weeks for 76 weeks during the PC period.
Participants received BIIB092, 600 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.
Participants received BIIB092, 2000 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.
Overall Number of Participants Analyzed 214 58 58 106 214
Measure Type: Number
Unit of Measure: percentage of participants
AEs 84.6 86.2 82.8 88.7 88.3
SAEs 12.1 10.3 10.3 12.3 11.7
2.Primary Outcome
Title LTE Period: Percentage of Participants With AEs and SAEs
Hide Description An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose, results in death; in the view of the investigator places the participant at immediate risk of death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event.
Time Frame From Week 80 to Week 173
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all randomized participants who received at least one dose of study treatment (BIIB092 or placebo).
Arm/Group Title LTE Period: BIIB092 125 mg/4 Week LTE Period: BIIB092 375 mg/12 Week LTE Period: BIIB092 600 mg/4 Week LTE Period: BIIB092 2000 mg/4 Week - Early Start LTE Period: BIIB092 2000 mg/4 Week - Late Start
Hide Arm/Group Description:
Participants who received BIIB092, 125 mg, IV infusion during the PC Period, continued to receive BIIB092, 125 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period.
Participants who received BIIB092, 375 mg, IV infusion during the PC Period, continued to receive BIIB092, 375 mg, IV infusion once every 12 weeks from Week 80 to Week 155 during the LTE period.
Participants who received BIIB092, 600 mg, IV infusion during the PC period, continued to receive BIIB092, 600 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period.
Participants who received BIIB092, 2000 mg, IV infusion during the PC period, continued to receive BIIB092, 2000 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period.
Participants who received BIIB092-matching placebo, IV infusion during the PC period, received BIIB092, 2000 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period.
Overall Number of Participants Analyzed 45 49 89 168 165
Measure Type: Number
Unit of Measure: percentage of participants
AEs 68.9 55.1 58.4 61.3 60.0
SAEs 11.1 2.0 10.1 6.0 7.9
3.Secondary Outcome
Title PC Period: Change From Baseline Over Time at Week 78 on the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score
Hide Description The CDR-SB is a validated clinical assessment of global function in participants with AD. The CDR is comprised of 6 domains: Memory, Orientation, Judgment and Problem Solving, Community Affairs, Home and Hobbies, and Personal Care. CDR-SB is the sum of the scores for these 6 domains. Impairment is scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or "box scores", can be added together to give the CDR-SB score which ranges from 0 (none) to 18 (severe impairment).
Time Frame Baseline, Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomized participants who received study treatment (BIIB092 or placebo). As pre-specified in study protocol, 125 mg and 375 mg groups were pooled as 'Low dose' group for efficacy analyses.
Arm/Group Title PC Period: Placebo PC Period: BIIB092 Low Dose PC Period: BIIB092 600 mg/4 Week PC Period: BIIB092 2000 mg/4 Week
Hide Arm/Group Description:
Participants received BIIB092-matching placebo, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.
Participants received BIIB092, 125 mg, IV infusion, on Day 1 and then once every 4 weeks or BIIB092, 375 mg, IV infusion, on Day 1 and then once every 12 weeks for 76 weeks during the PC period.
Participants received BIIB092, 600 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.
Participants received BIIB092, 2000 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.
Overall Number of Participants Analyzed 214 116 106 214
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 214 participants 116 participants 106 participants 214 participants
3.07  (1.467) 2.92  (1.620) 3.24  (1.557) 3.04  (1.378)
Change at Week 78 Number Analyzed 170 participants 98 participants 91 participants 174 participants
1.71  (2.376) 2.10  (2.375) 2.23  (2.987) 1.76  (2.038)
4.Secondary Outcome
Title PC Period: Percentage of Participants With Anti-BIIB092 Antibodies in Serum
Hide Description [Not Specified]
Time Frame Baseline up to Week 76
Hide Outcome Measure Data
Hide Analysis Population Description
The ADA evaluable set is defined as participants in the FAS who have an evaluable postbaseline ADA sample.
Arm/Group Title PC Period: Placebo PC Period: BIIB092 125 mg/4 Week PC Period: BIIB092 375 mg/12 Week PC Period: BIIB092 600 mg/4 Week PC Period: BIIB092 2000 mg/4 Week
Hide Arm/Group Description:
Participants received BIIB092-matching placebo, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.
Participants received BIIB092, 125 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.
Participants received BIIB092, 375 mg, IV infusion, on Day 1 and then once every 12 weeks for 76 weeks during the PC period.
Participants received BIIB092, 600 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.
Participants received BIIB092, 2000 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.
Overall Number of Participants Analyzed 211 57 57 105 212
Measure Type: Number
Unit of Measure: percentage of participants
1.9 0 0 1.0 0
Time Frame From first dose through 14 weeks after last dose of study drug (Up to approximately 173 weeks)
Adverse Event Reporting Description The safety analysis set included all randomized participants who received at least one dose of study treatment (BIIB092 or placebo). The all-cause mortality data and adverse events are reported for 'safety analysis set'.
 
Arm/Group Title PC Period: Placebo PC Period: BIIB092 125 mg/4 Week PC Period: BIIB092 375 mg/12 Week PC Period: BIIB092 600 mg/4 Week PC Period: BIIB092 2000 mg/4 Week LTE Period: BIIB092 125 mg/4 Week LTE Period: BIIB092 375 mg/12 Week LTE Period: BIIB092 600 mg/4 Week LTE Period: BIIB092 2000 mg/4 Week - Early Start LTE Period: BIIB092 2000 mg/4 Week - Late Start
Hide Arm/Group Description Participants received BIIB092-matching placebo, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period. Participants received BIIB092, 125 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period. Participants received BIIB092, 375 mg, IV infusion, on Day 1 and then once every 12 weeks for 76 weeks during the PC period. Participants received BIIB092, 600 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period. Participants received BIIB092, 2000 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period. Participants who received BIIB092, 125 mg, IV infusion during the PC period, continued to receive BIIB092, 125 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period. Participants who received BIIB092, 375 mg, IV infusion during the PC period, continued to receive BIIB092, 375 mg, IV infusion once every 12 weeks from Week 80 to Week 155 during the LTE period. Participants who received BIIB092, 600 mg, IV infusion during the PC period, continued to receive BIIB092, 600 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period. Participants who received BIIB092, 2000 mg, IV infusion during the PC period, continued to receive BIIB092, 2000 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period. Participants who received BIIB092-matching placebo, IV infusion during the PC period, received BIIB092, 2000 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period.
All-Cause Mortality
PC Period: Placebo PC Period: BIIB092 125 mg/4 Week PC Period: BIIB092 375 mg/12 Week PC Period: BIIB092 600 mg/4 Week PC Period: BIIB092 2000 mg/4 Week LTE Period: BIIB092 125 mg/4 Week LTE Period: BIIB092 375 mg/12 Week LTE Period: BIIB092 600 mg/4 Week LTE Period: BIIB092 2000 mg/4 Week - Early Start LTE Period: BIIB092 2000 mg/4 Week - Late Start
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/214 (0.47%)   1/58 (1.72%)   0/58 (0.00%)   0/106 (0.00%)   1/214 (0.47%)   2/45 (4.44%)   0/49 (0.00%)   1/89 (1.12%)   1/168 (0.60%)   1/165 (0.61%) 
Hide Serious Adverse Events
PC Period: Placebo PC Period: BIIB092 125 mg/4 Week PC Period: BIIB092 375 mg/12 Week PC Period: BIIB092 600 mg/4 Week PC Period: BIIB092 2000 mg/4 Week LTE Period: BIIB092 125 mg/4 Week LTE Period: BIIB092 375 mg/12 Week LTE Period: BIIB092 600 mg/4 Week LTE Period: BIIB092 2000 mg/4 Week - Early Start LTE Period: BIIB092 2000 mg/4 Week - Late Start
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   26/214 (12.15%)   6/58 (10.34%)   6/58 (10.34%)   13/106 (12.26%)   25/214 (11.68%)   5/45 (11.11%)   1/49 (2.04%)   9/89 (10.11%)   10/168 (5.95%)   13/165 (7.88%) 
Blood and lymphatic system disorders                     
Anaemia † 1  0/214 (0.00%)  1/58 (1.72%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Cardiac disorders                     
Acute myocardial infarction † 1  0/214 (0.00%)  1/58 (1.72%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Angina pectoris † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Atrial fibrillation † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Bradycardia † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Coronary artery disease † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  2/106 (1.89%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Coronary artery stenosis † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  1/165 (0.61%) 
Cardiac failure congestive † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  1/168 (0.60%)  0/165 (0.00%) 
Myocardial infarction † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  1/45 (2.22%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Ear and labyrinth disorders                     
Vertigo positional † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  1/165 (0.61%) 
Eye disorders                     
Cataract † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Idiopathic orbital inflammation † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  1/89 (1.12%)  0/168 (0.00%)  0/165 (0.00%) 
Gastrointestinal disorders                     
Constipation † 1  0/214 (0.00%)  1/58 (1.72%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Dysphagia † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Enterovesical fistula † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Faecaloma † 1  0/214 (0.00%)  1/58 (1.72%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Gastritis erosive † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Gastrointestinal haemorrhage † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  1/106 (0.94%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Gastrooesophageal reflux disease † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Hiatus hernia † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Inguinal hernia † 1  0/214 (0.00%)  0/58 (0.00%)  1/58 (1.72%)  1/106 (0.94%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Large intestinal stenosis † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Umbilical hernia † 1  0/214 (0.00%)  1/58 (1.72%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Colitis † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  1/165 (0.61%) 
Oesophageal ulcer haemorrhage † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  1/45 (2.22%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Rectal prolapse † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  1/165 (0.61%) 
Small intestinal obstruction † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  1/165 (0.61%) 
Hepatobiliary disorders                     
Hepatitis acute † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  1/89 (1.12%)  0/168 (0.00%)  0/165 (0.00%) 
Infections and infestations                     
Appendicitis † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  1/165 (0.61%) 
Atypical pneumonia † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
COVID-19 pneumonia † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  1/89 (1.12%)  0/168 (0.00%)  1/165 (0.61%) 
Escherichia sepsis † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Escherichia urinary tract infection † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Infection † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Pelvic abscess † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Pneumonia † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  1/106 (0.94%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  1/89 (1.12%)  1/168 (0.60%)  0/165 (0.00%) 
Sepsis † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  1/89 (1.12%)  0/168 (0.00%)  0/165 (0.00%) 
Upper respiratory tract infection † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Urinary tract infection † 1  0/214 (0.00%)  0/58 (0.00%)  1/58 (1.72%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  1/89 (1.12%)  0/168 (0.00%)  1/165 (0.61%) 
Peritonsillar abscess † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  1/168 (0.60%)  0/165 (0.00%) 
Respiratory tract infection † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  1/89 (1.12%)  0/168 (0.00%)  0/165 (0.00%) 
Retroperitoneal abscess † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  1/165 (0.61%) 
Injury, poisoning and procedural complications                     
Concussion † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Contusion † 1  0/214 (0.00%)  0/58 (0.00%)  1/58 (1.72%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Fall † 1  2/214 (0.93%)  1/58 (1.72%)  1/58 (1.72%)  1/106 (0.94%)  1/214 (0.47%)  0/45 (0.00%)  1/49 (2.04%)  0/89 (0.00%)  3/168 (1.79%)  3/165 (1.82%) 
Femur fracture † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Hip fracture † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  1/106 (0.94%)  0/214 (0.00%)  1/45 (2.22%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  1/165 (0.61%) 
Ligament sprain † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  1/165 (0.61%) 
Post lumbar puncture syndrome † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  1/106 (0.94%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Rib fracture † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Subdural haematoma † 1  0/214 (0.00%)  0/58 (0.00%)  1/58 (1.72%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Thoracic vertebral fracture † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Alcohol poisoning † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  1/168 (0.60%)  0/165 (0.00%) 
Ankle fracture † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  1/165 (0.61%) 
Craniocerebral injury † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  1/168 (0.60%)  0/165 (0.00%) 
Femoral neck fracture † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  1/49 (2.04%)  0/89 (0.00%)  1/168 (0.60%)  0/165 (0.00%) 
Investigations                     
Electrocardiogram QT prolonged † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Metabolism and nutrition disorders                     
Dehydration † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  1/168 (0.60%)  0/165 (0.00%) 
Hypoglycaemia † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Musculoskeletal and connective tissue disorders                     
Osteoarthritis † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  2/106 (1.89%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Spinal stenosis † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Arthritis † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  1/89 (1.12%)  0/168 (0.00%)  0/165 (0.00%) 
Pain in extremity † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  1/165 (0.61%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                     
Basal cell carcinoma † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  1/168 (0.60%)  0/165 (0.00%) 
Bladder cancer recurrent † 1  0/214 (0.00%)  1/58 (1.72%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Breast cancer stage II † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Invasive breast carcinoma † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Malignant melanoma † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Oesophageal carcinoma † 1  0/214 (0.00%)  1/58 (1.72%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Ovarian cancer † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Pancreatic carcinoma metastatic † 1  0/214 (0.00%)  1/58 (1.72%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Pancreatic carcinoma stage III † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Papillary thyroid cancer † 1  0/214 (0.00%)  0/58 (0.00%)  1/58 (1.72%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Penile squamous cell carcinoma † 1  0/214 (0.00%)  0/58 (0.00%)  1/58 (1.72%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Prostate cancer † 1  0/214 (0.00%)  1/58 (1.72%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  1/165 (0.61%) 
Squamous cell carcinoma of lung † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Transitional cell carcinoma † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Colon cancer † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  1/165 (0.61%) 
Hepatocellular carcinoma † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  1/45 (2.22%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Nervous system disorders                     
Ataxia † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Dementia Alzheimer's type † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Dizziness † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Epilepsy † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  1/89 (1.12%)  0/168 (0.00%)  0/165 (0.00%) 
Haemorrhagic stroke † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Presyncope † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Seizure † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  1/106 (0.94%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  1/89 (1.12%)  1/168 (0.60%)  0/165 (0.00%) 
Syncope † 1  1/214 (0.47%)  1/58 (1.72%)  0/58 (0.00%)  1/106 (0.94%)  2/214 (0.93%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  1/168 (0.60%)  0/165 (0.00%) 
Toxic encephalopathy † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Transient ischaemic attack † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  1/106 (0.94%)  0/214 (0.00%)  1/45 (2.22%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  1/165 (0.61%) 
Product Issues                     
Device dislocation † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  1/49 (2.04%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Psychiatric disorders                     
Delusion † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  1/165 (0.61%) 
Mental status changes † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  1/168 (0.60%)  0/165 (0.00%) 
Depression † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Hallucination † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Renal and urinary disorders                     
Acute kidney injury † 1  0/214 (0.00%)  1/58 (1.72%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Nephrolithiasis † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Reproductive system and breast disorders                     
Benign prostatic hyperplasia † 1  1/214 (0.47%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Female genital tract fistula † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  1/106 (0.94%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Respiratory, thoracic and mediastinal disorders                     
Organising pneumonia † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Pneumonia aspiration † 1  1/214 (0.47%)  1/58 (1.72%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Pneumothorax † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  2/214 (0.93%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Pulmonary embolism † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Acute respiratory failure † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  1/165 (0.61%) 
Pneumonitis † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  1/45 (2.22%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Respiratory failure † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  1/168 (0.60%)  0/165 (0.00%) 
Vascular disorders                     
Aortic aneurysm † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  1/106 (0.94%)  0/214 (0.00%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Hypertensive crisis † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Orthostatic hypotension † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Deep vein thrombosis † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  1/45 (2.22%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
1
Term from vocabulary, MedDRA 23.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
PC Period: Placebo PC Period: BIIB092 125 mg/4 Week PC Period: BIIB092 375 mg/12 Week PC Period: BIIB092 600 mg/4 Week PC Period: BIIB092 2000 mg/4 Week LTE Period: BIIB092 125 mg/4 Week LTE Period: BIIB092 375 mg/12 Week LTE Period: BIIB092 600 mg/4 Week LTE Period: BIIB092 2000 mg/4 Week - Early Start LTE Period: BIIB092 2000 mg/4 Week - Late Start
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   121/214 (56.54%)   39/58 (67.24%)   38/58 (65.52%)   68/106 (64.15%)   139/214 (64.95%)   10/45 (22.22%)   11/49 (22.45%)   19/89 (21.35%)   28/168 (16.67%)   29/165 (17.58%) 
Gastrointestinal disorders                     
Constipation † 1  8/214 (3.74%)  5/58 (8.62%)  1/58 (1.72%)  2/106 (1.89%)  6/214 (2.80%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Diarrhoea † 1  12/214 (5.61%)  11/58 (18.97%)  3/58 (5.17%)  6/106 (5.66%)  11/214 (5.14%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Nausea † 1  13/214 (6.07%)  4/58 (6.90%)  2/58 (3.45%)  6/106 (5.66%)  11/214 (5.14%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
General disorders                     
Fatigue † 1  7/214 (3.27%)  1/58 (1.72%)  4/58 (6.90%)  8/106 (7.55%)  12/214 (5.61%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Infections and infestations                     
Nasopharyngitis † 1  22/214 (10.28%)  4/58 (6.90%)  6/58 (10.34%)  9/106 (8.49%)  24/214 (11.21%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Sinusitis † 1  2/214 (0.93%)  3/58 (5.17%)  0/58 (0.00%)  1/106 (0.94%)  7/214 (3.27%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Upper respiratory tract infection † 1  15/214 (7.01%)  5/58 (8.62%)  3/58 (5.17%)  6/106 (5.66%)  15/214 (7.01%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Urinary tract infection † 1  13/214 (6.07%)  5/58 (8.62%)  3/58 (5.17%)  8/106 (7.55%)  20/214 (9.35%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
COVID-19 † 1  0/214 (0.00%)  0/58 (0.00%)  0/58 (0.00%)  0/106 (0.00%)  0/214 (0.00%)  2/45 (4.44%)  1/49 (2.04%)  9/89 (10.11%)  2/168 (1.19%)  3/165 (1.82%) 
Injury, poisoning and procedural complications                     
Fall † 1  23/214 (10.75%)  6/58 (10.34%)  11/58 (18.97%)  19/106 (17.92%)  30/214 (14.02%)  5/45 (11.11%)  7/49 (14.29%)  6/89 (6.74%)  14/168 (8.33%)  15/165 (9.09%) 
Contusion † 1  6/214 (2.80%)  0/58 (0.00%)  1/58 (1.72%)  8/106 (7.55%)  5/214 (2.34%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Limb injury † 1  0/214 (0.00%)  1/58 (1.72%)  3/58 (5.17%)  1/106 (0.94%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Investigations                     
Weight decreased † 1  4/214 (1.87%)  2/58 (3.45%)  3/58 (5.17%)  3/106 (2.83%)  5/214 (2.34%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Metabolism and nutrition disorders                     
Decreased appetite † 1  2/214 (0.93%)  3/58 (5.17%)  0/58 (0.00%)  0/106 (0.00%)  2/214 (0.93%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Musculoskeletal and connective tissue disorders                     
Arthralgia † 1  14/214 (6.54%)  6/58 (10.34%)  7/58 (12.07%)  9/106 (8.49%)  19/214 (8.88%)  0/45 (0.00%)  3/49 (6.12%)  4/89 (4.49%)  6/168 (3.57%)  3/165 (1.82%) 
Back pain † 1  16/214 (7.48%)  5/58 (8.62%)  3/58 (5.17%)  9/106 (8.49%)  13/214 (6.07%)  3/45 (6.67%)  0/49 (0.00%)  2/89 (2.25%)  5/168 (2.98%)  5/165 (3.03%) 
Muscle spasms † 1  3/214 (1.40%)  3/58 (5.17%)  0/58 (0.00%)  3/106 (2.83%)  7/214 (3.27%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Neck pain † 1  2/214 (0.93%)  3/58 (5.17%)  0/58 (0.00%)  2/106 (1.89%)  5/214 (2.34%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Nervous system disorders                     
Dizziness † 1  13/214 (6.07%)  5/58 (8.62%)  2/58 (3.45%)  9/106 (8.49%)  11/214 (5.14%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Headache † 1  20/214 (9.35%)  1/58 (1.72%)  6/58 (10.34%)  11/106 (10.38%)  22/214 (10.28%)  1/45 (2.22%)  3/49 (6.12%)  4/89 (4.49%)  3/168 (1.79%)  6/165 (3.64%) 
Psychiatric disorders                     
Anxiety † 1  11/214 (5.14%)  4/58 (6.90%)  2/58 (3.45%)  3/106 (2.83%)  15/214 (7.01%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Confusional state † 1  5/214 (2.34%)  4/58 (6.90%)  0/58 (0.00%)  4/106 (3.77%)  2/214 (0.93%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Depression † 1  13/214 (6.07%)  4/58 (6.90%)  2/58 (3.45%)  4/106 (3.77%)  11/214 (5.14%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Disorientation † 1  2/214 (0.93%)  3/58 (5.17%)  1/58 (1.72%)  1/106 (0.94%)  1/214 (0.47%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Irritability † 1  2/214 (0.93%)  3/58 (5.17%)  2/58 (3.45%)  3/106 (2.83%)  3/214 (1.40%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Renal and urinary disorders                     
Pollakiuria † 1  0/214 (0.00%)  3/58 (5.17%)  1/58 (1.72%)  0/106 (0.00%)  3/214 (1.40%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Respiratory, thoracic and mediastinal disorders                     
Cough † 1  5/214 (2.34%)  1/58 (1.72%)  3/58 (5.17%)  7/106 (6.60%)  16/214 (7.48%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Rhinorrhoea † 1  1/214 (0.47%)  1/58 (1.72%)  3/58 (5.17%)  1/106 (0.94%)  2/214 (0.93%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
Vascular disorders                     
Hypertension † 1  14/214 (6.54%)  5/58 (8.62%)  3/58 (5.17%)  6/106 (5.66%)  13/214 (6.07%)  0/45 (0.00%)  0/49 (0.00%)  0/89 (0.00%)  0/168 (0.00%)  0/165 (0.00%) 
1
Term from vocabulary, MedDRA 23.1
†
Indicates events were collected by systematic assessment
The study was terminated based on lack of efficacy following the placebo-controlled period readout.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Our agreement is subject to confidentiality but generally the PI can publish, for non-commercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: US Biogen Clinical Trial Center
Organization: Biogen
Phone: 866-633-4636
EMail: clinicaltrials@biogen.com
Layout table for additonal information
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT03352557    
Other Study ID Numbers: 251AD201
2017-002901-37 ( EudraCT Number )
First Submitted: November 21, 2017
First Posted: November 24, 2017
Results First Submitted: August 26, 2022
Results First Posted: November 8, 2022
Last Update Posted: November 8, 2022