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

• ClinicalTrials.gov Identifier: NCT01900665
• Recruitment Status: Terminated
• First Posted: July 16, 2013
• Results First Posted: March 14, 2018
• Last Update Posted: October 9, 2019
• Sponsor: Eli Lilly and Company
• 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

Participant Flow

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
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.

Baseline Characteristics

Arm/Group Title		Solanezumab	Placebo	Total
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
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

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive 14 Item Subscore (ADAS-Cog14)
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

Outcome Measure Data

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
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)

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)
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

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
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
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

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title	Solanezumab	Placebo
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
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

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title		Solanezumab	Placebo
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)
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

Outcome Measure Data

Analysis Population Description

All randomized participants.

Arm/Group Title		Solanezumab	Placebo
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)
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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)

Adverse Events

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
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	--/--		--/--		--/--		--/--
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
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

Limitations and Caveats

[Not Specified]

More Information

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Honig LS, Vellas B, Woodward M, Boada M, Bullock R, Borrie M, Hager K, Andreasen N, Scarpini E, Liu-Seifert H, Case M, Dean RA, Hake A, Sundell K, Poole Hoffmann V, Carlson C, Khanna R, Mintun M, DeMattos R, Selzler KJ, Siemers E. Trial of Solanezumab for Mild Dementia Due to Alzheimer's Disease. N Engl J Med. 2018 Jan 25;378(4):321-330. doi: 10.1056/NEJMoa1705971.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01900665
• 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: October 9, 2019