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Progress of Mild Alzheimer's Disease in Participants on Solanezumab Versus Placebo (EXPEDITION 3)

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ClinicalTrials.gov Identifier: NCT01900665
Recruitment Status : Terminated (Solanezumab did not meet the study's primary endpoint.)
First Posted : July 16, 2013
Results First Posted : March 14, 2018
Last Update Posted : May 3, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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: Solanezumab
Drug: Placebo
Enrollment 2129
Recruitment Details  
Pre-assignment Details Participants were excluded after study enrollment,if PET imaging or CSF results did not show evidence of brain amyloid pathology,a screening MRI with results >4 ARIA-H(amyloid-related imaging abnormality-hemorrhage/hemosiderin deposition) or presence of ARIA-E(amyloid-related imaging abnormality-edema/effusions) and abnormal lab results were found.
Arm/Group Title Solanezumab Placebo
Hide Arm/Group Description Participants received Solanezumab 400 milligrams (mg)Intravenously (IV) every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks. Participants received Placebo IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.
Period Title: Placebo Controlled Period
Started 1057 1072
Received at Least 1 Dose of Study Drug 1054 1067
Completed 914 908
Not Completed 143 164
Reason Not Completed
Death             9             16
Adverse Event             48             39
Protocol Violation             1             7
Withdrawal by Subject             33             45
Physician Decision             11             7
Lost to Follow-up             3             0
Caregiver Decision             33             41
Entry Criteria Not Met             5             9
Period Title: Open Label Period
Started 881 [1] 859 [1]
Completed 0 0
Not Completed 881 859
Reason Not Completed
Adverse Event             16             20
Death             5             6
Lost to Follow-up             1             1
Parent/Caregiver Decision             33             34
Physician Decision             4             4
Protocol Violation             0             1
Sponsor Decision             802             765
Withdrawal by Subject             20             28
[1]
Patients from Placebo Controlled Period were not required to enter into Open Label Period.
Arm/Group Title Solanezumab Placebo Total
Hide Arm/Group Description Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.

Placebo every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.

Placebo: Administered IV

Total of all reporting groups
Overall Number of Baseline Participants 1057 1072 2129
Hide Baseline Analysis Population Description
All randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1057 participants 1072 participants 2129 participants
72.69  (7.814) 73.26  (7.966) 72.98  (7.894)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1057 participants 1072 participants 2129 participants
Female 600 631 1231
Male 457 441 898
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 970 participants 986 participants 1956 participants
Hispanic or Latino 49 49 98
Not Hispanic or Latino 921 937 1858
Unknown or Not Reported 0 0 0
[1]
Measure Analysis Population Description: All randomized participants who had baseline ethnicity data.
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 970 participants 986 participants 1956 participants
American Indian or Alaska Native 0 0 0
Asian 75 71 146
Native Hawaiian or Other Pacific Islander 1 0 1
Black or African American 14 19 33
White 878 894 1772
More than one race 2 2 4
Unknown or Not Reported 0 0 0
[1]
Measure Analysis Population Description: All randomized participants who had baseline race data.
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Canada Number Analyzed 1057 participants 1072 participants 2129 participants
61 66 127
Sweden Number Analyzed 1057 participants 1072 participants 2129 participants
26 26 52
United States Number Analyzed 1057 participants 1072 participants 2129 participants
537 541 1078
Japan Number Analyzed 1057 participants 1072 participants 2129 participants
67 65 132
Poland Number Analyzed 1057 participants 1072 participants 2129 participants
52 50 102
Italy Number Analyzed 1057 participants 1072 participants 2129 participants
46 52 98
United Kingdom Number Analyzed 1057 participants 1072 participants 2129 participants
45 44 89
Australia Number Analyzed 1057 participants 1072 participants 2129 participants
32 36 68
France Number Analyzed 1057 participants 1072 participants 2129 participants
87 86 173
Germany Number Analyzed 1057 participants 1072 participants 2129 participants
48 48 96
Spain Number Analyzed 1057 participants 1072 participants 2129 participants
56 58 114
1.Primary Outcome
Title Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive 14 Item Subscore (ADAS-Cog14)
Hide Description The ADAS is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS that was used as the primary efficacy measure consists of 14 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation, and maze completion measures. The ADAS-Cog14 scale ranges from 0 to 90. Higher scores indicate greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
Time Frame Baseline, Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had baseline and post baseline data.
Arm/Group Title Solanezumab Placebo
Hide Arm/Group Description:
Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.
Participants received Placebo IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.
Overall Number of Participants Analyzed 1053 1067
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
6.65  (0.355) 7.44  (0.356)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Solanezumab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.095
Comments [Not Specified]
Method Mixed Models Analysis
Comments The Kenward-Roger approximation was used to estimate the denominator degrees of freedom.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.80
Confidence Interval (2-Sided) 95%
-1.73 to 0.14
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Alzheimer's Disease Cooperative Study- Instrumental Activities of Daily Living (ADCS-iADL)
Hide Description The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant’s caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The total score ranges from 0 to 78, with lower scores indicating greater disease severity. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
Time Frame Baseline, Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had baseline and post baseline data.
Arm/Group Title Solanezumab Placebo
Hide Arm/Group Description:
Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.
Participants received Placebo IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.
Overall Number of Participants Analyzed 908 896
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-6.17  (0.318) -7.17  (0.320)
3.Secondary Outcome
Title Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive 11 Item Subscore (ADAS-Cog11)
Hide Description The cognitive subscale of ADAS (ADAS Cog11) consists of 11 items assessing areas of function most typically impaired in Alzheimer’s disease (AD): orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
Time Frame Baseline, Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had baseline and post baseline data.
Arm/Group Title Solanezumab Placebo
Hide Arm/Group Description:
Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.
Participants received Placebo IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.
Overall Number of Participants Analyzed 1053 1067
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
5.22  (0.284) 5.90  (0.285)
4.Secondary Outcome
Title Change From Baseline in Mini-Mental State Examination (MMSE)
Hide Description MMSE is a brief screening instrument used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures) in elderly participants. Total score ranges from 0 to 30; lower score indicates greater disease severity. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
Time Frame Baseline, Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had baseline and post baseline data.
Arm/Group Title Solanezumab Placebo
Hide Arm/Group Description:
Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.
Participants received Placebo IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.
Overall Number of Participants Analyzed 893 876
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-3.17  (0.154) -3.66  (0.156)
5.Secondary Outcome
Title Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL)
Hide Description The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant’s caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The total score ranges from 0 to 78, with lower scores indicating greater disease severity. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
Time Frame Baseline, Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had baseline and post baseline data.
Arm/Group Title Solanezumab Placebo
Hide Arm/Group Description:
Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.
Participants received Placebo IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.
Overall Number of Participants Analyzed 908 897
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-7.42  (0.386) -8.77  (0.387)
6.Secondary Outcome
Title Change From Baseline in Functional Activities Questionnaire (FAQ)
Hide Description FAQ is a 10-item, caregiver-based questionnaire and was administered to the study partner who was asked to rate the participant’s ability to perform a variety of activities ranging from financial management, shopping, playing games, food preparation, traveling, keeping appointments, keeping track of current events, and understanding media. FAQ total score was calculated by adding the scores from each of the 10 items. A negative change indicated an improvement from baseline. FAQ Total Score is the sum of 10 items, ranging from 0 (best possible outcome) to 100 (worst possible outcome). LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
Time Frame Baseline, Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had baseline and post baseline data.
Arm/Group Title Solanezumab Placebo
Hide Arm/Group Description:
Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.
Participants received Placebo IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.
Overall Number of Participants Analyzed 907 892
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
5.17  (0.212) 5.57  (0.213)
7.Secondary Outcome
Title Change From Baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB)
Hide Description CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
Time Frame Baseline, Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had baseline and post baseline data.
Arm/Group Title Solanezumab Placebo
Hide Arm/Group Description:
Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.
Participants received Placebo IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.
Overall Number of Participants Analyzed 903 895
Mean (Standard Deviation)
Unit of Measure: Units on a scale
1.91  (2.442) 2.23  (2.692)
8.Secondary Outcome
Title Change From Baseline in Neuropsychiatric Inventory (NPI)
Hide Description NPI assesses psychopathology in participants with dementia and other neurologic disorders. Information is obtained from a caregiver familiar with the participant’s behavior. Total score ranges from 12 to 144; Higher scores indicate greater disease severity. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
Time Frame Baseline, Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had baseline and post baseline data.
Arm/Group Title Solanezumab Placebo
Hide Arm/Group Description:
Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.
Participants received Placebo IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.
Overall Number of Participants Analyzed 909 891
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
2.26  (3.11) 0.382  (0.387)
9.Secondary Outcome
Title Change From Baseline in Resource Utilization in Dementia-Lite (RUD-Lite)
Hide Description Assesses healthcare resource utilization (formal and informal care). Information gathered on both caregivers (care-giving time, work status) and participants (accommodation and healthcare resource utilization) was gathered from baseline and follow-up interviews. Reported number of hospitalizations per participant up to 76 weeks. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
Time Frame Baseline, Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had baseline and post baseline data.
Arm/Group Title Solanezumab Placebo
Hide Arm/Group Description:
Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.

Placebo every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.

Placebo: Administered IV

Overall Number of Participants Analyzed 909 891
Least Squares Mean (Standard Error)
Unit of Measure: Number of hospitalizations
Basic ADL 0.34  (0.058) 0.35  (0.058)
Instrumental ADL 0.55  (0.099) 0.50  (0.100)
Sum of Basic and Instrumental ADL 0.91  (0.132) 0.86  (0.134)
Supervision 0.72  (0.125) 0.88  (0.127)
10.Secondary Outcome
Title Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD)
Hide Description Assesses QoL for AD: participant rates mood, relationships, memory, finances, physical condition, and overall QoL assessment. Each of 13 items, rated on a 4-point scale. Sum of items=total score (range: 13 to 52). Higher scores indicate greater QoL. Participant’s primary caregiver asked to complete same measure. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
Time Frame Baseline, Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had baseline and post baseline data.
Arm/Group Title Solanezumab Placebo
Hide Arm/Group Description:
Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.
Participants received Placebo IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.
Overall Number of Participants Analyzed 853 812
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-0.55  (0.158) -0.72  (0.161)
11.Secondary Outcome
Title Change From Baseline in 5-Dimensional EuroQol Quality of Life Scale Proxy Version (EQ-5D Proxy)
Hide Description EQ-5D (proxy version) measures mobility, self-care, usual activities, pain/discomfort, anxiety/depression. 3 severity levels: no, some, severe problems. Visual analog scale (VAS) assesses caregiver's impression of participant's health state; score ranges: 0 to 100 millimeter (mm). Lower scores=greater disease severity LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
Time Frame Baseline, Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had baseline and post baseline data.
Arm/Group Title Solanezumab Placebo
Hide Arm/Group Description:
Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.
Participants received Placebo IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.
Overall Number of Participants Analyzed 904 892
Least Squares Mean (Standard Error)
Unit of Measure: mm
-1.10  (0.556) -2.61  (0.562)
12.Secondary Outcome
Title Change From Baseline in Integrated Alzheimer’s Disease Rating Scale (iADRS)
Hide Description Integrated Alzheimer’s Disease Rating Scale is used to assess that solanezumab slows down the cognitive and functional decline associated with AD compared with placebo. iADRS is a simple linear combination of ADAS-Cog 13 or 14 and the ADCS-iADL. The scale ranges from 0 to 146, where lower scores indicate worse performance. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
Time Frame Baseline, Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had baseline and post baseline data.
Arm/Group Title Solanezumab Placebo
Hide Arm/Group Description:
Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.
Participants received Placebo IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.
Overall Number of Participants Analyzed 903 883
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-12.92  (0.533) -14.59  (0.537)
13.Secondary Outcome
Title Percentage of Participants of Cognitive and Functional Responders
Hide Description Assess the proportion of participants who reach certain levels of cognitive and functional decline. Decline in cognition was defined as worsening from baseline by at least 6 or 9 points on the ADAS Cog14. If there is a cognitive decline of a specified cut-off or more at any time then the participant is considered a nonresponder. Functional nonresponders are participants who have not had any of the following at any time point: Clinically evident decline in ability to perform one or more basic ADL present at baseline; A clinically evident decline in ability to perform 20% or more of the instrumental ADL present at baseline; An increase in global CDR score of 1 point or more compared with baseline. A decline from no impairment to mild impairment (bADL, iADL is not considered clinically significant, but other declines of 1 or more points and any participant discontinuation within the first 6 months will be considered a non-responder.
Time Frame Baseline through Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Solanezumab Placebo
Hide Arm/Group Description:
Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.
Participants received Placebo IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.
Overall Number of Participants Analyzed 1057 1072
Measure Type: Number
Unit of Measure: percentage of participants
Cognitive Responders: Cut-off 6 35.7 35.3
Cognitive Responders: Cut-off 9 55.2 52.3
Functional Responders 38.0 36.8
14.Secondary Outcome
Title Change From Baseline in Plasma Amyloid-Beta (Aβ) Species
Hide Description Concentration of amino acid peptide known as Aβ 1-42 in plasma. The change in plasma Aβ analytes after treatment were assessed separately for each plasma Aβ parameter. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
Time Frame Baseline, Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Solanezumab Placebo
Hide Arm/Group Description:
Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.
Participants received Placebo IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.
Overall Number of Participants Analyzed 1057 1072
Least Squares Mean (Standard Error)
Unit of Measure: Picogram/milliliter
Modified amyloid beta 1-40 Number Analyzed 841 participants 842 participants
172754.36  (1613.534) 262.98  (1609.006)
Modified amyloid beta1-42 Number Analyzed 848 participants 840 participants
18485.26  (104.913) 15.75  (105.237)
15.Secondary Outcome
Title Change From Baseline in Volumetric Magnetic Resonance Imaging (vMRI)
Hide Description The vMRI assessment of right and left hippocampal atrophy, is reported. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
Time Frame Baseline, Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Solanezumab Placebo
Hide Arm/Group Description:
Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.
Participants received Placebo IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.
Overall Number of Participants Analyzed 1057 1072
Mean (Standard Deviation)
Unit of Measure: Cubic millimeter (mm^3)
Right hippocampal atrophy Number Analyzed 789 participants 771 participants
-145.7  (75.42) -154.1  (81.06)
Left hippocampal atrophy Number Analyzed 789 participants 771 participants
-142.3  (74.27) -146.3  (78.04)
Right hippocampal atrophy+Left hippocampal atrophy Number Analyzed 789 participants 771 participants
-288.0  (135.19) -300.4  (138.52)
Right entorhinal cortex atrophy Number Analyzed 789 participants 771 participants
-77.3  (45.18) -80.8  (45.16)
Left entorhinal cortex atrophy Number Analyzed 789 participants 771 participants
-91.6  (47.60) -95.2  (53.46)
Right+Left entorhinal cortex atrophy Number Analyzed 789 participants 771 participants
-169.0  (79.65) -176.0  (86.11)
Atrophy of whole brain volume Number Analyzed 786 participants 769 participants
-22725.6  (11920.78) -23500.5  (12000.09)
Enlargement of Ventricular volume Number Analyzed 788 participants 770 participants
7055.4  (4580.36) 7226.6  (4545.73)
16.Secondary Outcome
Title Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Solanezumab (LY2062430)
Hide Description Area Under the Concentration versus Time Curve was evaluated for Solanezumab.
Time Frame Visit 2 (Post-dose), Visit 5, 9, 15 (Pre-dose, Post-dose) and Visit 22 (Pre-dose): Pre-dose before the infusion, Post-dose 30 minutes End of Infusion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study medication (Solanezumab) with evaluable Solanezumab PK data.
Arm/Group Title Solanezumab
Hide Arm/Group Description:
Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.
Overall Number of Participants Analyzed 1044
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: milligram*hour per milliliter (mg*h/mL)
43.2
(24.3%)
17.Secondary Outcome
Title Change From Baseline in Florbetapir Positron Emission Tomography (PET) Scan
Hide Description Florbetapir PET imaging was used to confirm the presence of amyloid pathology consistent with AD. Change from baseline was done to test the hypothesis that amyloid burden was reduced in participants in the treatment group. The change from baseline to the postbaseline visit of the composite summary standard uptake value ratio of florbetapir F18 was calculated. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit. The composite summary measure is an unweighted average of the 6 smaller regions (anterior cingulate, frontal medial orbital, parietal, posterior cingulate, precuneus, and temporal) normalized to whole cerebellum or subject-specific white matter.
Time Frame Baseline, Week 80
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had baseline and post baseline data.
Arm/Group Title Solanezumab Placebo
Hide Arm/Group Description:
Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.
Participants received Placebo IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.
Overall Number of Participants Analyzed 915 924
Least Squares Mean (Standard Error)
Unit of Measure: standard uptake value ratio
Subject specific white matter corrected Number Analyzed 805 participants 791 participants
0.02  (0.002) 0.02  (0.002)
Mean whole cerebellum corrected Number Analyzed 805 participants 791 participants
-0.01  (0.005) 0.00  (0.005)
18.Secondary Outcome
Title Change From Baseline in Cerebrospinal Fluid (CSF) Aβ Levels
Hide Description Concentration of CSF parameters includes amino acid peptide known as Aβ 1-42 and Aβ 1-42. Analyses of these CSF biomarkers was conducted in a subset of participants (as an addendum to the protocol). The dependent variable for each CSF parameter was its change from baseline to endpoint. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
Time Frame Baseline, Week 80
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Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug and had baseline and post baseline data.
Arm/Group Title Solanezumab Placebo
Hide Arm/Group Description:
Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.
Participants received Placebo IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.
Overall Number of Participants Analyzed 1057 1072
Least Squares Mean (Standard Error)
Unit of Measure: picogram/milliliter
Free amyloid beta 1-42, CSF -37.33  (7.507) -9.27  (8.175)
Modified amyloid beta 1-42, CSF 315.69  (42.620) -107.91  (42.907)
Time Frame Up To 80 Weeks
Adverse Event Reporting Description All randomized participants who received at least 1 dose of study drug.
 
Arm/Group Title Solanezumab: Double-Blind Phase Placebo: Double-Blind Phase Solanezumab: Open Label Placebo: Open Label
Hide Arm/Group Description Participants received Solanezumab 400 mg IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who completed the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks. Participants received Placebo IV every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks. Participants who complete 80 weeks treatment/assessment of the double-blind period were entered into open-label period. Participants received Solanezumab 400 mg IV every 4 weeks for 180 weeks with an additional 4 weeks of assessments. Participants who complete 80 weeks treatment/assessment of the double-blind period were entered into open-label period. Participants received Placebo IV every 4 weeks for 180 weeks with an additional 4 weeks of assessments.
All-Cause Mortality
Solanezumab: Double-Blind Phase Placebo: Double-Blind Phase Solanezumab: Open Label Placebo: Open Label
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Solanezumab: Double-Blind Phase Placebo: Double-Blind Phase Solanezumab: Open Label Placebo: Open Label
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   175/1054 (16.60%)      203/1067 (19.03%)      102/879 (11.60%)      114/856 (13.32%)    
Blood and lymphatic system disorders         
Anaemia  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Lymphadenitis  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Cardiac disorders         
Acute myocardial infarction  1  1/1054 (0.09%)  1 2/1067 (0.19%)  2 0/879 (0.00%)  0 0/856 (0.00%)  0
Adams-stokes syndrome  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Angina pectoris  1  3/1054 (0.28%)  3 2/1067 (0.19%)  2 0/879 (0.00%)  0 1/856 (0.12%)  1
Aortic valve stenosis  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Arrhythmia supraventricular  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Atrial fibrillation  1  5/1054 (0.47%)  5 9/1067 (0.84%)  9 4/879 (0.46%)  4 5/856 (0.58%)  5
Atrioventricular block  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Atrioventricular block complete  1  0/1054 (0.00%)  0 2/1067 (0.19%)  2 0/879 (0.00%)  0 0/856 (0.00%)  0
Atrioventricular block second degree  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 1/879 (0.11%)  1 0/856 (0.00%)  0
Bradycardia  1  2/1054 (0.19%)  2 2/1067 (0.19%)  2 2/879 (0.23%)  2 3/856 (0.35%)  3
Cardiac arrest  1  1/1054 (0.09%)  1 3/1067 (0.28%)  3 0/879 (0.00%)  0 1/856 (0.12%)  1
Cardiac failure  1  0/1054 (0.00%)  0 3/1067 (0.28%)  3 0/879 (0.00%)  0 1/856 (0.12%)  1
Cardiac failure congestive  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 2/879 (0.23%)  2 2/856 (0.23%)  2
Cardio-respiratory arrest  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Coronary artery disease  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Myocardial infarction  1  2/1054 (0.19%)  2 4/1067 (0.37%)  4 2/879 (0.23%)  2 1/856 (0.12%)  1
Myocardial ischaemia  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Sinus bradycardia  1  0/1054 (0.00%)  0 2/1067 (0.19%)  2 0/879 (0.00%)  0 3/856 (0.35%)  3
Sinus node dysfunction  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Ear and labyrinth disorders         
Vertigo  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 2/879 (0.23%)  2 1/856 (0.12%)  1
Vertigo positional  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Endocrine disorders         
Toxic nodular goitre  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Eye disorders         
Cataract  1  1/1054 (0.09%)  2 1/1067 (0.09%)  1 1/879 (0.11%)  2 1/856 (0.12%)  1
Glaucoma  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Open angle glaucoma  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Retinal detachment  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Gastrointestinal disorders         
Abdominal pain  1  3/1054 (0.28%)  3 3/1067 (0.28%)  3 1/879 (0.11%)  1 0/856 (0.00%)  0
Abdominal pain upper  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Colitis ulcerative  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Diarrhoea  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Duodenal perforation  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Gastric ulcer  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Gastrointestinal disorder  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Gastrointestinal haemorrhage  1  2/1054 (0.19%)  2 2/1067 (0.19%)  2 1/879 (0.11%)  1 0/856 (0.00%)  0
Gastrooesophageal reflux disease  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Haemorrhoidal haemorrhage  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Haemorrhoids  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Hernial eventration  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Hiatus hernia  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Inguinal hernia  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Intestinal obstruction  1  2/1054 (0.19%)  2 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Intestinal perforation  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Intestinal polyp  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Large intestine polyp  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Lower gastrointestinal haemorrhage  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Mallory-weiss syndrome  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Nausea  1  2/1054 (0.19%)  2 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Oesophageal rupture  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Pancreatitis acute  1  2/1054 (0.19%)  2 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Peptic ulcer haemorrhage  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Rectal prolapse  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Retroperitoneal haematoma  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Small intestinal obstruction  1  1/1054 (0.09%)  1 3/1067 (0.28%)  3 1/879 (0.11%)  1 1/856 (0.12%)  1
Upper gastrointestinal haemorrhage  1  0/1054 (0.00%)  0 3/1067 (0.28%)  3 0/879 (0.00%)  0 1/856 (0.12%)  1
Vomiting  1  0/1054 (0.00%)  0 2/1067 (0.19%)  3 0/879 (0.00%)  0 0/856 (0.00%)  0
General disorders         
Asthenia  1  0/1054 (0.00%)  0 2/1067 (0.19%)  2 2/879 (0.23%)  2 0/856 (0.00%)  0
Chest discomfort  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 1/879 (0.11%)  1 0/856 (0.00%)  0
Chest pain  1  3/1054 (0.28%)  3 0/1067 (0.00%)  0 1/879 (0.11%)  1 1/856 (0.12%)  1
Death  1  1/1054 (0.09%)  1 2/1067 (0.19%)  2 0/879 (0.00%)  0 0/856 (0.00%)  0
Gait disturbance  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
General physical health deterioration  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Generalised oedema  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Multiple organ dysfunction syndrome  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Non-cardiac chest pain  1  7/1054 (0.66%)  8 5/1067 (0.47%)  7 1/879 (0.11%)  1 1/856 (0.12%)  1
Pain  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Pyrexia  1  3/1054 (0.28%)  3 0/1067 (0.00%)  0 0/879 (0.00%)  0 2/856 (0.23%)  2
Stent-graft endoleak  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Sudden death  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Systemic inflammatory response syndrome  1  2/1054 (0.19%)  2 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Hepatobiliary disorders         
Bile duct stone  1  2/1054 (0.19%)  2 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Cholangitis  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Cholecystitis  1  0/1054 (0.00%)  0 1/1067 (0.09%)  2 0/879 (0.00%)  0 1/856 (0.12%)  1
Cholecystitis acute  1  2/1054 (0.19%)  2 2/1067 (0.19%)  2 0/879 (0.00%)  0 1/856 (0.12%)  1
Cholelithiasis  1  2/1054 (0.19%)  2 0/1067 (0.00%)  0 2/879 (0.23%)  2 0/856 (0.00%)  0
Gallbladder perforation  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Hepatotoxicity  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Jaundice cholestatic  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Portal vein thrombosis  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Infections and infestations         
Abdominal abscess  1  2/1054 (0.19%)  2 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Appendicitis perforated  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Atypical mycobacterial pneumonia  1  0/1054 (0.00%)  0 1/1067 (0.09%)  2 0/879 (0.00%)  0 0/856 (0.00%)  0
Atypical pneumonia  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Bacteraemia  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Bacterial infection  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Bacterial sepsis  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Bronchitis  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 2/879 (0.23%)  2 0/856 (0.00%)  0
Cellulitis  1  1/1054 (0.09%)  1 2/1067 (0.19%)  2 0/879 (0.00%)  0 1/856 (0.12%)  1
Chronic sinusitis  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Clostridium difficile infection  1  0/1054 (0.00%)  0 2/1067 (0.19%)  4 0/879 (0.00%)  0 0/856 (0.00%)  0
Escherichia sepsis  1  0/1054 (0.00%)  0 2/1067 (0.19%)  2 0/879 (0.00%)  0 0/856 (0.00%)  0
Extradural abscess  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Furuncle  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Gastroenteritis  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Gastroenteritis viral  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Hepatitis e  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Herpes zoster  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Influenza  1  2/1054 (0.19%)  2 1/1067 (0.09%)  1 1/879 (0.11%)  1 0/856 (0.00%)  0
Intervertebral discitis  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Localised infection  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Lung abscess  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Meningoencephalitis herpetic  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Oesophageal candidiasis  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Ophthalmic herpes zoster  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Orchitis  1  0/455 (0.00%)  0 0/440 (0.00%)  0 0/378 (0.00%)  0 1/348 (0.29%)  1
Osteomyelitis bacterial  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Paraspinal abscess  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Pelvic abscess  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Peritonitis  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Pneumonia  1  11/1054 (1.04%)  11 8/1067 (0.75%)  8 3/879 (0.34%)  3 5/856 (0.58%)  5
Pneumonia influenzal  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Pyelonephritis  1  1/1054 (0.09%)  1 3/1067 (0.28%)  3 1/879 (0.11%)  1 1/856 (0.12%)  1
Sepsis  1  0/1054 (0.00%)  0 2/1067 (0.19%)  2 1/879 (0.11%)  1 0/856 (0.00%)  0
Septic shock  1  2/1054 (0.19%)  2 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Tooth infection  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Upper respiratory tract infection  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Urinary tract infection  1  2/1054 (0.19%)  2 8/1067 (0.75%)  9 2/879 (0.23%)  2 3/856 (0.35%)  3
Urosepsis  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Viral infection  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 3/879 (0.34%)  3 0/856 (0.00%)  0
Wound infection  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Injury, poisoning and procedural complications         
Alcohol poisoning  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Animal bite  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 1/879 (0.11%)  1 0/856 (0.00%)  0
Ankle fracture  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Arthropod sting  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Cervical vertebral fracture  1  2/1054 (0.19%)  3 1/1067 (0.09%)  1 1/879 (0.11%)  1 1/856 (0.12%)  1
Chest injury  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Clavicle fracture  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Concussion  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Contusion  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 2/856 (0.23%)  2
Coronary vascular graft occlusion  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Craniocerebral injury  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Fall  1  24/1054 (2.28%)  26 24/1067 (2.25%)  27 5/879 (0.57%)  5 12/856 (1.40%)  12
Femoral neck fracture  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 2/856 (0.23%)  2
Femur fracture  1  6/1054 (0.57%)  7 5/1067 (0.47%)  5 3/879 (0.34%)  3 1/856 (0.12%)  1
Fibula fracture  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Fracture displacement  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Fractured coccyx  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Gastrointestinal stoma complication  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Gun shot wound  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Head injury  1  2/1054 (0.19%)  2 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Hip fracture  1  5/1054 (0.47%)  5 6/1067 (0.56%)  6 3/879 (0.34%)  3 3/856 (0.35%)  3
Humerus fracture  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 1/879 (0.11%)  1 0/856 (0.00%)  0
Joint dislocation  1  1/1054 (0.09%)  2 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Laceration  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Ligament sprain  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Lumbar vertebral fracture  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Pelvic fracture  1  0/1054 (0.00%)  0 2/1067 (0.19%)  2 1/879 (0.11%)  1 2/856 (0.23%)  2
Periprosthetic fracture  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Postoperative ileus  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Pubis fracture  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Radius fracture  1  2/1054 (0.19%)  2 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Rib fracture  1  1/1054 (0.09%)  1 4/1067 (0.37%)  4 0/879 (0.00%)  0 1/856 (0.12%)  1
Road traffic accident  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Skull fracture  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Spinal compression fracture  1  0/1054 (0.00%)  0 2/1067 (0.19%)  2 1/879 (0.11%)  1 3/856 (0.35%)  3
Spinal fracture  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 1/856 (0.12%)  1
Sternal fracture  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Subdural haematoma  1  2/1054 (0.19%)  2 4/1067 (0.37%)  4 1/879 (0.11%)  1 1/856 (0.12%)  1
Upper limb fracture  1  1/1054 (0.09%)  1 2/1067 (0.19%)  2 0/879 (0.00%)  0 1/856 (0.12%)  1
Wound  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Wrist fracture  1  2/1054 (0.19%)  2 1/1067 (0.09%)  1 1/879 (0.11%)  1 0/856 (0.00%)  0
Investigations         
Heart rate irregular  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Troponin t increased  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Weight decreased  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 1/879 (0.11%)  1 1/856 (0.12%)  1
Metabolism and nutrition disorders         
Cachexia  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Decreased appetite  1  0/1054 (0.00%)  0 2/1067 (0.19%)  2 0/879 (0.00%)  0 0/856 (0.00%)  0
Dehydration  1  3/1054 (0.28%)  3 4/1067 (0.37%)  4 3/879 (0.34%)  3 2/856 (0.23%)  2
Diabetic ketoacidosis  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Hyponatraemia  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Hypovolaemia  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Metabolic acidosis  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Musculoskeletal and connective tissue disorders         
Back pain  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 1/879 (0.11%)  1 0/856 (0.00%)  0
Foot deformity  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 1/879 (0.11%)  2 0/856 (0.00%)  0
Lumbar spinal stenosis  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Musculoskeletal chest pain  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Osteoarthritis  1  2/1054 (0.19%)  2 3/1067 (0.28%)  3 2/879 (0.23%)  2 1/856 (0.12%)  1
Osteonecrosis  1  3/1054 (0.28%)  3 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Rhabdomyolysis  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Spinal osteoarthritis  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Spondylolisthesis  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Tenosynovitis  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Abdominal neoplasm  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Adenocarcinoma of colon  1  1/1054 (0.09%)  1 2/1067 (0.19%)  2 0/879 (0.00%)  0 0/856 (0.00%)  0
B-cell lymphoma  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Basal cell carcinoma  1  2/1054 (0.19%)  3 2/1067 (0.19%)  3 0/879 (0.00%)  0 0/856 (0.00%)  0
Benign small intestinal neoplasm  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Bladder cancer  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Bladder neoplasm  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Breast cancer  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 2/856 (0.23%)  2
Breast cancer metastatic  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Cardiac myxoma  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Clear cell renal cell carcinoma  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Colon adenoma  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Colon cancer  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 1/879 (0.11%)  1 0/856 (0.00%)  0
Endometrial adenocarcinoma  1  0/599 (0.00%)  0 1/627 (0.16%)  1 0/501 (0.00%)  0 0/508 (0.00%)  0
Glioblastoma  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Glioblastoma multiforme  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Hepatic neoplasm  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Intraductal proliferative breast lesion  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Invasive ductal breast carcinoma  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Lip squamous cell carcinoma  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Lung adenocarcinoma  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Lung cancer metastatic  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Lung neoplasm malignant  1  1/1054 (0.09%)  1 2/1067 (0.19%)  2 0/879 (0.00%)  0 0/856 (0.00%)  0
Malignant melanoma  1  0/1054 (0.00%)  0 2/1067 (0.19%)  2 0/879 (0.00%)  0 1/856 (0.12%)  1
Malignant melanoma in situ  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Metastases to central nervous system  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Metastatic neoplasm  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Oesophageal adenocarcinoma  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Ovarian cancer stage iv  1  0/599 (0.00%)  0 1/627 (0.16%)  1 0/501 (0.00%)  0 0/508 (0.00%)  0
Pancreatic neoplasm  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Parathyroid tumour benign  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Plasma cell myeloma  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Prostate cancer  1  2/455 (0.44%)  2 0/440 (0.00%)  0 2/378 (0.53%)  2 0/348 (0.00%)  0
Prostate cancer metastatic  1  1/455 (0.22%)  1 1/440 (0.23%)  1 0/378 (0.00%)  0 1/348 (0.29%)  1
Rectal adenocarcinoma  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Renal cell carcinoma  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Small cell lung cancer  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Squamous cell carcinoma of the tongue  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Transitional cell cancer of renal pelvis and ureter metastatic  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Transitional cell carcinoma  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Uterine cancer  1  1/599 (0.17%)  1 0/627 (0.00%)  0 0/501 (0.00%)  0 0/508 (0.00%)  0
Nervous system disorders         
Altered state of consciousness  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Basal ganglia infarction  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Carotid artery stenosis  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Cerebellar haemorrhage  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Cerebellar infarction  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Cerebral haemorrhage  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 1/879 (0.11%)  1 0/856 (0.00%)  0
Cerebral infarction  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 3/879 (0.34%)  4 0/856 (0.00%)  0
Cerebrovascular accident  1  0/1054 (0.00%)  0 5/1067 (0.47%)  7 0/879 (0.00%)  0 3/856 (0.35%)  3
Cognitive disorder  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Coma  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Dementia  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 2/856 (0.23%)  2
Dementia alzheimer's type  1  1/1054 (0.09%)  1 2/1067 (0.19%)  2 0/879 (0.00%)  0 4/856 (0.47%)  5
Dementia of the alzheimer's type, with delirium  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Dizziness  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Embolic stroke  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Encephalopathy  1  1/1054 (0.09%)  1 2/1067 (0.19%)  2 0/879 (0.00%)  0 1/856 (0.12%)  1
Epilepsy  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 2/856 (0.23%)  2
Generalised tonic-clonic seizure  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Haemorrhage intracranial  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Haemorrhagic stroke  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Headache  1  1/1054 (0.09%)  1 3/1067 (0.28%)  3 0/879 (0.00%)  0 0/856 (0.00%)  0
Hypertensive encephalopathy  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Hypoaesthesia  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Ischaemic stroke  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Lacunar infarction  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Loss of consciousness  1  2/1054 (0.19%)  2 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Metabolic encephalopathy  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 1/879 (0.11%)  1 0/856 (0.00%)  0
Presyncope  1  3/1054 (0.28%)  3 1/1067 (0.09%)  1 0/879 (0.00%)  0 2/856 (0.23%)  2
Seizure  1  0/1054 (0.00%)  0 4/1067 (0.37%)  4 1/879 (0.11%)  1 1/856 (0.12%)  1
Somnolence  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Spinal cord compression  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Spinal epidural haematoma  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Subarachnoid haemorrhage  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Syncope  1  8/1054 (0.76%)  11 14/1067 (1.31%)  14 5/879 (0.57%)  5 7/856 (0.82%)  7
Thalamic infarction  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Thalamus haemorrhage  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Thrombotic cerebral infarction  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Tonic convulsion  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Transient ischaemic attack  1  2/1054 (0.19%)  2 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Pregnancy, puerperium and perinatal conditions         
Cephalhaematoma  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Product Issues         
Device dislocation  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Psychiatric disorders         
Abnormal behaviour  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Affective disorder  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Aggression  1  0/1054 (0.00%)  0 2/1067 (0.19%)  2 1/879 (0.11%)  1 2/856 (0.23%)  2
Agitation  1  3/1054 (0.28%)  3 2/1067 (0.19%)  2 1/879 (0.11%)  1 1/856 (0.12%)  1
Anxiety  1  2/1054 (0.19%)  2 2/1067 (0.19%)  2 0/879 (0.00%)  0 1/856 (0.12%)  1
Behavioural and psychiatric symptoms of dementia  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 2/879 (0.23%)  2 0/856 (0.00%)  0
Confusional state  1  3/1054 (0.28%)  3 1/1067 (0.09%)  1 2/879 (0.23%)  2 1/856 (0.12%)  1
Delirium  1  1/1054 (0.09%)  1 5/1067 (0.47%)  5 1/879 (0.11%)  1 1/856 (0.12%)  1
Delusion  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Depression  1  2/1054 (0.19%)  2 1/1067 (0.09%)  1 1/879 (0.11%)  1 0/856 (0.00%)  0
Disorientation  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Hallucination  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Mental status changes  1  2/1054 (0.19%)  2 4/1067 (0.37%)  4 0/879 (0.00%)  0 2/856 (0.23%)  3
Phobia  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Psychotic disorder  1  0/1054 (0.00%)  0 2/1067 (0.19%)  2 0/879 (0.00%)  0 0/856 (0.00%)  0
Suicide attempt  1  2/1054 (0.19%)  2 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Renal and urinary disorders         
Acute kidney injury  1  2/1054 (0.19%)  2 3/1067 (0.28%)  3 2/879 (0.23%)  2 3/856 (0.35%)  3
Nephrolithiasis  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Renal colic  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 2/879 (0.23%)  2 1/856 (0.12%)  1
Renal failure  1  0/1054 (0.00%)  0 2/1067 (0.19%)  2 0/879 (0.00%)  0 0/856 (0.00%)  0
Urinary bladder polyp  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Urinary incontinence  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Urinary retention  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 2/879 (0.23%)  2 0/856 (0.00%)  0
Reproductive system and breast disorders         
Benign prostatic hyperplasia  1  1/455 (0.22%)  1 1/440 (0.23%)  1 3/378 (0.79%)  3 0/348 (0.00%)  0
Prostatitis  1  1/455 (0.22%)  1 0/440 (0.00%)  0 0/378 (0.00%)  0 0/348 (0.00%)  0
Vulvar dysplasia  1  0/599 (0.00%)  0 1/627 (0.16%)  1 0/501 (0.00%)  0 0/508 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Acute respiratory failure  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Asthma  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 2/879 (0.23%)  2 1/856 (0.12%)  1
Chronic obstructive pulmonary disease  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Dyspnoea  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Epistaxis  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Organising pneumonia  1  0/1054 (0.00%)  0 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Pharyngeal mass  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Pleural effusion  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Pleurisy  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Pneumonia aspiration  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Pneumothorax  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 1/856 (0.12%)  1
Pulmonary embolism  1  4/1054 (0.38%)  4 2/1067 (0.19%)  2 1/879 (0.11%)  1 2/856 (0.23%)  2
Respiratory arrest  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Sleep apnoea syndrome  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 1/856 (0.12%)  1
Skin and subcutaneous tissue disorders         
Angioedema  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 1/879 (0.11%)  1 0/856 (0.00%)  0
Social circumstances         
Immobilisation prolonged  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Respite care  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 0/879 (0.00%)  0 0/856 (0.00%)  0
Vascular disorders         
Aortic aneurysm  1  3/1054 (0.28%)  3 0/1067 (0.00%)  0 2/879 (0.23%)  2 0/856 (0.00%)  0
Aortic stenosis  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Deep vein thrombosis  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Hypertension  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 2/879 (0.23%)  2 0/856 (0.00%)  0
Hypertensive crisis  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Hypotension  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 2/856 (0.23%)  2
Lymphoedema  1  1/1054 (0.09%)  1 0/1067 (0.00%)  0 1/879 (0.11%)  1 0/856 (0.00%)  0
Orthostatic hypotension  1  1/1054 (0.09%)  1 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Peripheral arterial occlusive disease  1  0/1054 (0.00%)  0 1/1067 (0.09%)  1 0/879 (0.00%)  0 0/856 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Solanezumab: Double-Blind Phase Placebo: Double-Blind Phase Solanezumab: Open Label Placebo: Open Label
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   536/1054 (50.85%)      530/1067 (49.67%)      255/879 (29.01%)      260/856 (30.37%)    
Gastrointestinal disorders         
Diarrhoea  1  76/1054 (7.21%)  86 87/1067 (8.15%)  109 23/879 (2.62%)  24 17/856 (1.99%)  18
Nausea  1  54/1054 (5.12%)  69 46/1067 (4.31%)  63 23/879 (2.62%)  32 15/856 (1.75%)  18
Infections and infestations         
Nasopharyngitis  1  89/1054 (8.44%)  114 80/1067 (7.50%)  99 29/879 (3.30%)  31 32/856 (3.74%)  36
Upper respiratory tract infection  1  64/1054 (6.07%)  74 54/1067 (5.06%)  61 23/879 (2.62%)  25 21/856 (2.45%)  23
Urinary tract infection  1  58/1054 (5.50%)  79 72/1067 (6.75%)  103 38/879 (4.32%)  47 36/856 (4.21%)  46
Injury, poisoning and procedural complications         
Fall  1  146/1054 (13.85%)  195 144/1067 (13.50%)  207 67/879 (7.62%)  97 80/856 (9.35%)  109
Musculoskeletal and connective tissue disorders         
Arthralgia  1  44/1054 (4.17%)  51 56/1067 (5.25%)  62 21/879 (2.39%)  23 22/856 (2.57%)  22
Back pain  1  63/1054 (5.98%)  70 60/1067 (5.62%)  67 26/879 (2.96%)  26 23/856 (2.69%)  23
Nervous system disorders         
Dizziness  1  61/1054 (5.79%)  66 57/1067 (5.34%)  65 23/879 (2.62%)  24 29/856 (3.39%)  31
Headache  1  86/1054 (8.16%)  96 86/1067 (8.06%)  151 28/879 (3.19%)  34 29/856 (3.39%)  42
Psychiatric disorders         
Anxiety  1  54/1054 (5.12%)  57 58/1067 (5.44%)  59 15/879 (1.71%)  18 17/856 (1.99%)  17
Depression  1  60/1054 (5.69%)  62 57/1067 (5.34%)  57 18/879 (2.05%)  18 20/856 (2.34%)  20
Respiratory, thoracic and mediastinal disorders         
Cough  1  44/1054 (4.17%)  53 58/1067 (5.44%)  69 25/879 (2.84%)  27 18/856 (2.10%)  22
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
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.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01900665     History of Changes
Other Study ID Numbers: 15136
H8A-MC-LZAX ( Other Identifier: Eli Lilly and Company )
First Submitted: July 12, 2013
First Posted: July 16, 2013
Results First Submitted: February 16, 2018
Results First Posted: March 14, 2018
Last Update Posted: May 3, 2018