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

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Terminated
CT.gov ID
NCT01900665
Collaborator
(none)
2,129
Enrollment
198
Locations
2
Arms
43.1
Duration (Months)
10.8
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To test the idea that solanezumab will slow the cognitive decline of Alzheimer's Disease (AD) as compared with placebo in participants with mild AD.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
2129 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Effect of Passive Immunization on the Progression of Mild Alzheimer's Disease: Solanezumab (LY2062430) Versus Placebo
Study Start Date :
Jul 1, 2013
Actual Primary Completion Date :
Oct 1, 2016
Actual Study Completion Date :
Feb 1, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Solanezumab

Solanezumab 400 milligrams (mg) 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 take this regimen for up to an additional 208 weeks.

Drug: Solanezumab
Administered Intravenously (IV)
Other Names:
  • LY2062430
  • A Beta Antibody

    		•
    Placebo Comparator: Placebo

    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.

    Drug: Placebo
    Administered IV

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive 14 Item Subscore (ADAS-Cog14) [Baseline, Week 80]

      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.

    Secondary Outcome Measures

    1. Change From Baseline in Alzheimer's Disease Cooperative Study- Instrumental Activities of Daily Living (ADCS-iADL) [Baseline, Week 80]

      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.

    2. Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive 11 Item Subscore (ADAS-Cog11) [Baseline, Week 80]

      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.

    3. Change From Baseline in Mini-Mental State Examination (MMSE) [Baseline, Week 80]

      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.

    4. Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) [Baseline, Week 80]

      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.

    5. Change From Baseline in Functional Activities Questionnaire (FAQ) [Baseline, Week 80]

      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.

    6. Change From Baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) [Baseline, Week 80]

      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.

    7. Change From Baseline in Neuropsychiatric Inventory (NPI) [Baseline, Week 80]

      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.

    8. Change From Baseline in Resource Utilization in Dementia-Lite (RUD-Lite) [Baseline, Week 80]

      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.

    9. Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD) [Baseline, Week 80]

      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.

    10. Change From Baseline in 5-Dimensional EuroQol Quality of Life Scale Proxy Version (EQ-5D Proxy) [Baseline, Week 80]

      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.

    11. Change From Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) [Baseline, Week 80]

      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.

    12. Percentage of Participants of Cognitive and Functional Responders [Baseline through Week 80]

      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.

    13. Change From Baseline in Plasma Amyloid-Beta (Aβ) Species [Baseline, Week 80]

      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.

    14. Change From Baseline in Volumetric Magnetic Resonance Imaging (vMRI) [Baseline, Week 80]

      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.

    15. Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Solanezumab (LY2062430) [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]

      Area Under the Concentration versus Time Curve was evaluated for Solanezumab.

    16. Change From Baseline in Florbetapir Positron Emission Tomography (PET) Scan [Baseline, Week 80]

      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.

    17. Change From Baseline in Cerebrospinal Fluid (CSF) Aβ Levels [Baseline, Week 80]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    55 Years to 90 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Meets National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable AD

    • Has a Modified Hachinski Ischemia Scale score of less than or equal to 4

    • Has a Mini-Mental State Examination (MMSE) score of 20 through 26 at Screening visit

    • Has a Geriatric Depression Scale score of less than or equal to 6 (on the staff-administered short form)

    • Has had a magnetic resonance imaging (MRI) or computerized tomography (CT) scan performed within the past 2 years that has confirmed no findings inconsistent with a diagnosis of AD

    • Has a florbetapir positron emission tomography (PET) scan or cerebrospinal fluid (CSF) result consistent with the presence of amyloid pathology at screening

    Exclusion Criteria:

    • Does not have a reliable caregiver who is in frequent contact with the participant (defined as at least 10 hours per week), will accompany the participant to the office and/or be available by telephone at designated times, and will monitor administration of prescribed medications

    • Meets National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS/AIREN) criteria for vascular dementia

    • Has current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses of safety and efficacy in this study; or has a life expectancy of <2 years

    • Has had a history within the last 5 years of a serious infectious disease affecting the brain or head trauma resulting in protracted loss of consciousness

    • Has a history within the last 5 years of a primary or recurrent malignant disease with the exception of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with a normal prostate-specific antigen posttreatment

    • Has a known history of human immunodeficiency virus (HIV), clinically significant multiple or severe drug allergies, or severe posttreatment hypersensitivity reactions

    • Has received acetylcholinesterase inhibitor (AChEIs), memantine and/or other AD therapy for less than 4 months or has less than 2 months of stable therapy on these treatments

    • Has received medications that affect the central nervous system (CNS), except treatments for AD, for less than 4 weeks

    • Has a history of chronic alcohol or drug abuse/dependence within the past 5 years

    • Has a Visit 1 MRI with results showing >4 Amyloid-related Imaging Abnormality (ARIA), -hemorrhage /hemosiderin deposition (ARIA-H) or presence of ARIA-E (edema/effusions)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Xenoscience Phoenix Arizona United States 85004
    2 Banner Alzheimer's Institute Phoenix Arizona United States 85006
    3 St Josephs Hospital and Medical Center Phoenix Arizona United States 85013
    4 ANI Arizona Neurological Institute Research, PC Sun City Arizona United States 85351
    5 Banner Sun Health Research Institute Sun City Arizona United States 85351
    6 Center for Neurosciences Tucson Arizona United States 85718
    7 Arizona Health Sciences Center Tucson Arizona United States 85724
    8 American Neuropsychiatric Research Institute, Inc Carson California United States 90746
    9 Neurology Center of North Orange County Fullerton California United States 92835
    10 Institute for Memory Impairment & Neurological Disorders Irvine California United States 92697
    11 University of California - San Diego La Jolla California United States 92037
    12 Senior Clinical Trials, Inc. Laguna Hills California United States 92653
    13 Torrance Clinical Research Lomita California United States 90717
    14 Collaborative Neuroscience Network - CNS Long Beach California United States 90806
    15 Apostle Clinical Trials, Inc Long Beach California United States 90813
    16 Univ of Southern California Medical Center Los Angeles California United States 90033
    17 University of California Los Angeles School of Medicine Los Angeles California United States 90073
    18 UCLA Medical Center Los Angeles California United States 90095
    19 Hoag Memorial Hospital Newport Beach California United States 92663
    20 Pacific Neuroscience Medical Group Oxnard California United States 93030
    21 Anderson Clinical Research Redlands California United States 92374
    22 University of California, Davis - Health Systems Sacramento California United States 95817
    23 Artemis Institute for Clinical Research San Diego California United States 92103
    24 Pacific Research Network Inc San Diego California United States 92103
    25 Sharp Mesa Vista Hospital San Diego California United States 92123
    26 San Francisco Clinical Research Center San Francisco California United States 94109
    27 University of California, San Francisco San Francisco California United States 94158
    28 Apex Research Institute Santa Ana California United States 92705
    29 St. Joseph Health Santa Rosa California United States 95403
    30 California Neuroscience Research Sherman Oaks California United States 91403
    31 Radiant Research Denver Colorado United States 80239
    32 Associated Neurologists of Southern Connecticut Fairfield Connecticut United States 06824
    33 Institute for Neurodegenerative Disorders New Haven Connecticut United States 06510
    34 Yale University School of Medicine New Haven Connecticut United States 06520-8020
    35 Research Center for Clinical Studies Norwalk Connecticut United States 06851
    36 Christiana Care Research Institute Newark Delaware United States 19713
    37 Georgetown University Hospital Washington District of Columbia United States 20057
    38 Parkinson's Disease and Movement Disorders Boca Raton Florida United States 33486
    39 Quantum Laboratories Deerfield Beach Florida United States 33064
    40 Brain Matters Research Delray Beach Florida United States 33445
    41 Cohen Medical Associates P.A. Delray Beach Florida United States 33446
    42 Neuropsychiatric Research Center of Southwest Florida Fort Myers Florida United States 33912
    43 MD Clinical Hallandale Beach Florida United States 33009
    44 Galiz Research Hialeah Florida United States 33016
    45 Infinity Clinical Research . LLC Hollywood Florida United States 33021
    46 Jacksonville Center for Clinical Research Jacksonville Florida United States 32216
    47 Mayo Clinic of Jacksonville Jacksonville Florida United States 32224
    48 Miami Jewish Home and Hospital for the Aged Miami Florida United States 33137
    49 Renstar Medical Research Ocala Florida United States 34471
    50 Compass Research Orlando Florida United States 32806
    51 Neurology Clinical Research, Inc Sunrise Florida United States 33351-6637
    52 Axiom Research Tampa Florida United States 33609
    53 Stedman Clinical Trials Tampa Florida United States 33613
    54 University of South Florida Tampa Florida United States 33613
    55 Premiere Research Institute at Palm Beach Neurology West Palm Beach Florida United States 33407
    56 Atlanta Center of Medical Research Atlanta Georgia United States 30331
    57 Rush Alzheimer's Disease Center Chicago Illinois United States 60612
    58 Alexian Brothers Medical Center Elk Grove Village Illinois United States 60007
    59 Indiana University School of Medicine Indianapolis Indiana United States 46202
    60 University of Kansas Medical Center Kansas City Kansas United States 66160
    61 CTT Consultants Prairie Village Kansas United States 66206
    62 Heartland Research Associates Wichita Kansas United States 67207
    63 Via Christi Regional Medical Center Wichita Kansas United States 67214
    64 Baptist Physician's Lexington Lexington Kentucky United States 40503
    65 Private Office: J. Gary Booker Shreveport Louisiana United States 71104
    66 Maine Research Associates Auburn Maine United States 04210
    67 Maine Neurology Scarborough Maine United States 04074
    68 PharmaSite Research Inc Baltimore Maryland United States 21208
    69 McLean Hospital Belmont Massachusetts United States 02478
    70 Brigham and Womens Hospital Boston Massachusetts United States 02115
    71 Boston University Medical Center Boston Massachusetts United States 02118
    72 ActivMed Practices & Research, Inc Methuen Massachusetts United States 01844
    73 Boston Center for Memory Newton Massachusetts United States 02459
    74 Northern Michigan Neurology Traverse City Michigan United States 49684
    75 Hattiesburg Clinic Hattiesburg Mississippi United States 39401
    76 Univ of Nebraska Med Center Omaha Nebraska United States 68198
    77 Cleveland Clinic of Las Vegas Las Vegas Nevada United States 89106
    78 Las Vegas Radiology Las Vegas Nevada United States 89113
    79 AdvanceMed Research Lawrenceville New Jersey United States 08648
    80 Albuquerque Neurosciences Albuquerque New Mexico United States 87109
    81 Albany Medical College Albany New York United States 12206
    82 Dent Neurological Institute Amherst New York United States 14226
    83 SPRI Clinical Trials, LLC. Brooklyn New York United States 11235
    84 New York University Medical Center New York New York United States 10016
    85 Mount Sinai Medical Center New York New York United States 10029-6574
    86 Columbia University Medical Center New York New York United States 10032
    87 Richmond Behavorial Associates Staten Island New York United States 10312
    88 PMG Research of Charlotte, LLC Charlotte North Carolina United States 28203
    89 Behavioral Health Center Research Charlotte North Carolina United States 28211
    90 Guilford Neurologic Associates Greensboro North Carolina United States 27405
    91 Wake Research Associates Raleigh North Carolina United States 27612
    92 PMG Research of Winston-Salem, LLC Winston-Salem North Carolina United States 27103
    93 Valley Medical Research Centerville Ohio United States 45459
    94 Ohio State Univ College Of Medicine Columbus Ohio United States 43210
    95 Neurology Specialists Inc. Dayton Ohio United States 45417
    96 Insight Clinical Trials Shaker Heights Ohio United States 44122
    97 Red River Medical Center, LLC Oklahoma City Oklahoma United States 73112
    98 Cutting Edge Research Group Oklahoma City Oklahoma United States 73116
    99 The Corvallis Clinic P.C. Corvallis Oregon United States 97330
    100 Summit Research Network Inc Portland Oregon United States 97210
    101 Drexel University College of Medicine at EPPI Philadelphia Pennsylvania United States 19102
    102 University of Pittsburgh Medical Center Pittsburgh Pennsylvania United States 15213
    103 Rhode Island Mood & Memory Research Institute East Providence Rhode Island United States 02914
    104 Rhode Island Hospital Providence Rhode Island United States 02903
    105 Butler Hospital Providence Rhode Island United States 02906
    106 Roper St. Francis Healthcare Charleston South Carolina United States 29401
    107 Radiant Research Greer South Carolina United States 29651
    108 University Psychiatry Associates Avera Health Sioux Falls South Dakota United States 57105
    109 Quillen College of Medicine, East TN State University Johnson City Tennessee United States 37604
    110 Vanderbilt Univeristy School of Medicine Nashville Tennessee United States 37212
    111 Texas Neurology, PA Dallas Texas United States 75214
    112 University of Texas Southwestern Medical Center at Dallas Dallas Texas United States 75390
    113 Diagnostic Research Group San Antonio Texas United States 78229
    114 Radiant Research Murray Utah United States 84123
    115 University of Utah School of Medicine Salt Lake City Utah United States 84108
    116 The Memory Clinic Bennington Vermont United States 05201
    117 National Clinical Research - Norfolk Inc Norfolk Virginia United States 23502
    118 National Clinical Research - Richmond Richmond Virginia United States 23294
    119 Blue Ridge Research Center Roanoke Virginia United States 24018
    120 Veterans Affairs Puget Sound Health Care System Seattle Washington United States 98108
    121 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Darlinghurst New South Wales Australia 2010
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    Sponsors and Collaborators

    • Eli Lilly and Company

    Investigators

    • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01900665
    Other Study ID Numbers:
    • 15136
    • H8A-MC-LZAX
    First Posted:
    Jul 16, 2013
    Last Update Posted:
    Oct 9, 2019
    Last Verified:
    Sep 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Additional relevant MeSH terms:
    Alzheimer Disease

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 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
    Period Title: Placebo Controlled Period
    STARTED 881 859
    COMPLETED 0 0
    NOT COMPLETED 881 859

    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 Participants 1057 1072 2129
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    72.69
    (7.814)
    73.26
    (7.966)
    72.98
    (7.894)
    Sex: Female, Male (Count of Participants)
    Female
    600
    56.8%
    631
    58.9%
    1231
    57.8%
    Male
    457
    43.2%
    441
    41.1%
    898
    42.2%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    49
    4.6%
    49
    4.6%
    98
    4.6%
    Not Hispanic or Latino
    921
    87.1%
    937
    87.4%
    1858
    87.3%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    75
    7.1%
    71
    6.6%
    146
    6.9%
    Native Hawaiian or Other Pacific Islander
    1
    0.1%
    0
    0%
    1
    0%
    Black or African American
    14
    1.3%
    19
    1.8%
    33
    1.6%
    White
    878
    83.1%
    894
    83.4%
    1772
    83.2%
    More than one race
    2
    0.2%
    2
    0.2%
    4
    0.2%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    Canada
    61
    5.8%
    66
    6.2%
    127
    6%
    Sweden
    26
    2.5%
    26
    2.4%
    52
    2.4%
    United States
    537
    50.8%
    541
    50.5%
    1078
    50.6%
    Japan
    67
    6.3%
    65
    6.1%
    132
    6.2%
    Poland
    52
    4.9%
    50
    4.7%
    102
    4.8%
    Italy
    46
    4.4%
    52
    4.9%
    98
    4.6%
    United Kingdom
    45
    4.3%
    44
    4.1%
    89
    4.2%
    Australia
    32
    3%
    36
    3.4%
    68
    3.2%
    France
    87
    8.2%
    86
    8%
    173
    8.1%
    Germany
    48
    4.5%
    48
    4.5%
    96
    4.5%
    Spain
    56
    5.3%
    58
    5.4%
    114
    5.4%

    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.
    Measure Participants 1053 1067
    Least Squares Mean (Standard Error) [Units on a scale]
    6.65
    (0.355)
    7.44
    (0.356)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Solanezumab, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.095
    Comments
    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
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    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.
    Measure Participants 908 896
    Least Squares Mean (Standard Error) [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.
    Measure Participants 1053 1067
    Least Squares Mean (Standard Error) [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.
    Measure Participants 893 876
    Least Squares Mean (Standard Error) [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.
    Measure Participants 908 897
    Least Squares Mean (Standard Error) [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.
    Measure Participants 907 892
    Least Squares Mean (Standard Error) [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.
    Measure Participants 903 895
    Mean (Standard Deviation) [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.
    Measure Participants 909 891
    Least Squares Mean (Standard Error) [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
    Measure Participants 909 891
    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.
    Measure Participants 853 812
    Least Squares Mean (Standard Error) [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.
    Measure Participants 904 892
    Least Squares Mean (Standard Error) [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.
    Measure Participants 903 883
    Least Squares Mean (Standard Error) [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.
    Measure Participants 1057 1072
    Cognitive Responders: Cut-off 6
    35.7
    3.4%
    35.3
    3.3%
    Cognitive Responders: Cut-off 9
    55.2
    5.2%
    52.3
    4.9%
    Functional Responders
    38.0
    3.6%
    36.8
    3.4%
    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.
    Measure Participants 1057 1072
    Modified amyloid beta 1-40
    172754.36
    (1613.534)
    262.98
    (1609.006)
    Modified amyloid beta1-42
    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.
    Measure Participants 1057 1072
    Right hippocampal atrophy
    -145.7
    (75.42)
    -154.1
    (81.06)
    Left hippocampal atrophy
    -142.3
    (74.27)
    -146.3
    (78.04)
    Right hippocampal atrophy+Left hippocampal atrophy
    -288.0
    (135.19)
    -300.4
    (138.52)
    Right entorhinal cortex atrophy
    -77.3
    (45.18)
    -80.8
    (45.16)
    Left entorhinal cortex atrophy
    -91.6
    (47.60)
    -95.2
    (53.46)
    Right+Left entorhinal cortex atrophy
    -169.0
    (79.65)
    -176.0
    (86.11)
    Atrophy of whole brain volume
    -22725.6
    (11920.78)
    -23500.5
    (12000.09)
    Enlargement of Ventricular volume
    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.
    Measure Participants 1044
    Geometric Mean (Geometric Coefficient of Variation) [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.
    Measure Participants 915 924
    Subject specific white matter corrected
    0.02
    (0.002)
    0.02
    (0.002)
    Mean whole cerebellum corrected
    -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.
    Measure Participants 1057 1072
    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 (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    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 (16.6%) 203/1067 (19%) 102/879 (11.6%) 114/856 (13.3%)
    Blood and lymphatic system disorders
    Anaemia 1/1054 (0.1%) 1 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Lymphadenitis 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Cardiac disorders
    Acute myocardial infarction 1/1054 (0.1%) 1 2/1067 (0.2%) 2 0/879 (0%) 0 0/856 (0%) 0
    Adams-stokes syndrome 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Angina pectoris 3/1054 (0.3%) 3 2/1067 (0.2%) 2 0/879 (0%) 0 1/856 (0.1%) 1
    Aortic valve stenosis 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Arrhythmia supraventricular 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Atrial fibrillation 5/1054 (0.5%) 5 9/1067 (0.8%) 9 4/879 (0.5%) 4 5/856 (0.6%) 5
    Atrioventricular block 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Atrioventricular block complete 0/1054 (0%) 0 2/1067 (0.2%) 2 0/879 (0%) 0 0/856 (0%) 0
    Atrioventricular block second degree 0/1054 (0%) 0 1/1067 (0.1%) 1 1/879 (0.1%) 1 0/856 (0%) 0
    Bradycardia 2/1054 (0.2%) 2 2/1067 (0.2%) 2 2/879 (0.2%) 2 3/856 (0.4%) 3
    Cardiac arrest 1/1054 (0.1%) 1 3/1067 (0.3%) 3 0/879 (0%) 0 1/856 (0.1%) 1
    Cardiac failure 0/1054 (0%) 0 3/1067 (0.3%) 3 0/879 (0%) 0 1/856 (0.1%) 1
    Cardiac failure congestive 1/1054 (0.1%) 1 1/1067 (0.1%) 1 2/879 (0.2%) 2 2/856 (0.2%) 2
    Cardio-respiratory arrest 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Coronary artery disease 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Myocardial infarction 2/1054 (0.2%) 2 4/1067 (0.4%) 4 2/879 (0.2%) 2 1/856 (0.1%) 1
    Myocardial ischaemia 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Sinus bradycardia 0/1054 (0%) 0 2/1067 (0.2%) 2 0/879 (0%) 0 3/856 (0.4%) 3
    Sinus node dysfunction 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Ear and labyrinth disorders
    Vertigo 0/1054 (0%) 0 1/1067 (0.1%) 1 2/879 (0.2%) 2 1/856 (0.1%) 1
    Vertigo positional 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Endocrine disorders
    Toxic nodular goitre 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Eye disorders
    Cataract 1/1054 (0.1%) 2 1/1067 (0.1%) 1 1/879 (0.1%) 2 1/856 (0.1%) 1
    Glaucoma 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Open angle glaucoma 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Retinal detachment 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 3/1054 (0.3%) 3 3/1067 (0.3%) 3 1/879 (0.1%) 1 0/856 (0%) 0
    Abdominal pain upper 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Colitis ulcerative 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Diarrhoea 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Duodenal perforation 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Gastric ulcer 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Gastrointestinal disorder 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Gastrointestinal haemorrhage 2/1054 (0.2%) 2 2/1067 (0.2%) 2 1/879 (0.1%) 1 0/856 (0%) 0
    Gastrooesophageal reflux disease 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Haemorrhoidal haemorrhage 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Haemorrhoids 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Hernial eventration 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Hiatus hernia 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Inguinal hernia 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Intestinal obstruction 2/1054 (0.2%) 2 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Intestinal perforation 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Intestinal polyp 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Large intestine polyp 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Lower gastrointestinal haemorrhage 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Mallory-weiss syndrome 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Nausea 2/1054 (0.2%) 2 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Oesophageal rupture 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Pancreatitis acute 2/1054 (0.2%) 2 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Peptic ulcer haemorrhage 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Rectal prolapse 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Retroperitoneal haematoma 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Small intestinal obstruction 1/1054 (0.1%) 1 3/1067 (0.3%) 3 1/879 (0.1%) 1 1/856 (0.1%) 1
    Upper gastrointestinal haemorrhage 0/1054 (0%) 0 3/1067 (0.3%) 3 0/879 (0%) 0 1/856 (0.1%) 1
    Vomiting 0/1054 (0%) 0 2/1067 (0.2%) 3 0/879 (0%) 0 0/856 (0%) 0
    General disorders
    Asthenia 0/1054 (0%) 0 2/1067 (0.2%) 2 2/879 (0.2%) 2 0/856 (0%) 0
    Chest discomfort 0/1054 (0%) 0 1/1067 (0.1%) 1 1/879 (0.1%) 1 0/856 (0%) 0
    Chest pain 3/1054 (0.3%) 3 0/1067 (0%) 0 1/879 (0.1%) 1 1/856 (0.1%) 1
    Death 1/1054 (0.1%) 1 2/1067 (0.2%) 2 0/879 (0%) 0 0/856 (0%) 0
    Gait disturbance 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    General physical health deterioration 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Generalised oedema 1/1054 (0.1%) 1 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Multiple organ dysfunction syndrome 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Non-cardiac chest pain 7/1054 (0.7%) 8 5/1067 (0.5%) 7 1/879 (0.1%) 1 1/856 (0.1%) 1
    Pain 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Pyrexia 3/1054 (0.3%) 3 0/1067 (0%) 0 0/879 (0%) 0 2/856 (0.2%) 2
    Stent-graft endoleak 1/1054 (0.1%) 1 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Sudden death 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Systemic inflammatory response syndrome 2/1054 (0.2%) 2 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Hepatobiliary disorders
    Bile duct stone 2/1054 (0.2%) 2 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Cholangitis 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Cholecystitis 0/1054 (0%) 0 1/1067 (0.1%) 2 0/879 (0%) 0 1/856 (0.1%) 1
    Cholecystitis acute 2/1054 (0.2%) 2 2/1067 (0.2%) 2 0/879 (0%) 0 1/856 (0.1%) 1
    Cholelithiasis 2/1054 (0.2%) 2 0/1067 (0%) 0 2/879 (0.2%) 2 0/856 (0%) 0
    Gallbladder perforation 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Hepatotoxicity 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Jaundice cholestatic 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Portal vein thrombosis 1/1054 (0.1%) 1 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Infections and infestations
    Abdominal abscess 2/1054 (0.2%) 2 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Appendicitis perforated 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Atypical mycobacterial pneumonia 0/1054 (0%) 0 1/1067 (0.1%) 2 0/879 (0%) 0 0/856 (0%) 0
    Atypical pneumonia 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Bacteraemia 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Bacterial infection 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Bacterial sepsis 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Bronchitis 1/1054 (0.1%) 1 1/1067 (0.1%) 1 2/879 (0.2%) 2 0/856 (0%) 0
    Cellulitis 1/1054 (0.1%) 1 2/1067 (0.2%) 2 0/879 (0%) 0 1/856 (0.1%) 1
    Chronic sinusitis 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Clostridium difficile infection 0/1054 (0%) 0 2/1067 (0.2%) 4 0/879 (0%) 0 0/856 (0%) 0
    Escherichia sepsis 0/1054 (0%) 0 2/1067 (0.2%) 2 0/879 (0%) 0 0/856 (0%) 0
    Extradural abscess 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Furuncle 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Gastroenteritis 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Gastroenteritis viral 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Hepatitis e 1/1054 (0.1%) 1 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Herpes zoster 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Influenza 2/1054 (0.2%) 2 1/1067 (0.1%) 1 1/879 (0.1%) 1 0/856 (0%) 0
    Intervertebral discitis 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Localised infection 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Lung abscess 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Meningoencephalitis herpetic 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Oesophageal candidiasis 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Ophthalmic herpes zoster 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Orchitis 0/455 (0%) 0 0/440 (0%) 0 0/378 (0%) 0 1/348 (0.3%) 1
    Osteomyelitis bacterial 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Paraspinal abscess 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Pelvic abscess 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Peritonitis 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Pneumonia 11/1054 (1%) 11 8/1067 (0.7%) 8 3/879 (0.3%) 3 5/856 (0.6%) 5
    Pneumonia influenzal 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Pyelonephritis 1/1054 (0.1%) 1 3/1067 (0.3%) 3 1/879 (0.1%) 1 1/856 (0.1%) 1
    Sepsis 0/1054 (0%) 0 2/1067 (0.2%) 2 1/879 (0.1%) 1 0/856 (0%) 0
    Septic shock 2/1054 (0.2%) 2 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Tooth infection 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Upper respiratory tract infection 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Urinary tract infection 2/1054 (0.2%) 2 8/1067 (0.7%) 9 2/879 (0.2%) 2 3/856 (0.4%) 3
    Urosepsis 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Viral infection 0/1054 (0%) 0 0/1067 (0%) 0 3/879 (0.3%) 3 0/856 (0%) 0
    Wound infection 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Injury, poisoning and procedural complications
    Alcohol poisoning 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Animal bite 0/1054 (0%) 0 1/1067 (0.1%) 1 1/879 (0.1%) 1 0/856 (0%) 0
    Ankle fracture 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Arthropod sting 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Cervical vertebral fracture 2/1054 (0.2%) 3 1/1067 (0.1%) 1 1/879 (0.1%) 1 1/856 (0.1%) 1
    Chest injury 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Clavicle fracture 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Concussion 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Contusion 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 2/856 (0.2%) 2
    Coronary vascular graft occlusion 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Craniocerebral injury 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Fall 24/1054 (2.3%) 26 24/1067 (2.2%) 27 5/879 (0.6%) 5 12/856 (1.4%) 12
    Femoral neck fracture 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 2/856 (0.2%) 2
    Femur fracture 6/1054 (0.6%) 7 5/1067 (0.5%) 5 3/879 (0.3%) 3 1/856 (0.1%) 1
    Fibula fracture 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Fracture displacement 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Fractured coccyx 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Gastrointestinal stoma complication 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Gun shot wound 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Head injury 2/1054 (0.2%) 2 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Hip fracture 5/1054 (0.5%) 5 6/1067 (0.6%) 6 3/879 (0.3%) 3 3/856 (0.4%) 3
    Humerus fracture 0/1054 (0%) 0 1/1067 (0.1%) 1 1/879 (0.1%) 1 0/856 (0%) 0
    Joint dislocation 1/1054 (0.1%) 2 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Laceration 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Ligament sprain 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Lumbar vertebral fracture 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Pelvic fracture 0/1054 (0%) 0 2/1067 (0.2%) 2 1/879 (0.1%) 1 2/856 (0.2%) 2
    Periprosthetic fracture 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Postoperative ileus 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Pubis fracture 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Radius fracture 2/1054 (0.2%) 2 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Rib fracture 1/1054 (0.1%) 1 4/1067 (0.4%) 4 0/879 (0%) 0 1/856 (0.1%) 1
    Road traffic accident 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Skull fracture 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Spinal compression fracture 0/1054 (0%) 0 2/1067 (0.2%) 2 1/879 (0.1%) 1 3/856 (0.4%) 3
    Spinal fracture 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 1/856 (0.1%) 1
    Sternal fracture 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Subdural haematoma 2/1054 (0.2%) 2 4/1067 (0.4%) 4 1/879 (0.1%) 1 1/856 (0.1%) 1
    Upper limb fracture 1/1054 (0.1%) 1 2/1067 (0.2%) 2 0/879 (0%) 0 1/856 (0.1%) 1
    Wound 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Wrist fracture 2/1054 (0.2%) 2 1/1067 (0.1%) 1 1/879 (0.1%) 1 0/856 (0%) 0
    Investigations
    Heart rate irregular 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Troponin t increased 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Weight decreased 1/1054 (0.1%) 1 0/1067 (0%) 0 1/879 (0.1%) 1 1/856 (0.1%) 1
    Metabolism and nutrition disorders
    Cachexia 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Decreased appetite 0/1054 (0%) 0 2/1067 (0.2%) 2 0/879 (0%) 0 0/856 (0%) 0
    Dehydration 3/1054 (0.3%) 3 4/1067 (0.4%) 4 3/879 (0.3%) 3 2/856 (0.2%) 2
    Diabetic ketoacidosis 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Hyponatraemia 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Hypovolaemia 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Metabolic acidosis 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Musculoskeletal and connective tissue disorders
    Back pain 0/1054 (0%) 0 1/1067 (0.1%) 1 1/879 (0.1%) 1 0/856 (0%) 0
    Foot deformity 1/1054 (0.1%) 1 0/1067 (0%) 0 1/879 (0.1%) 2 0/856 (0%) 0
    Lumbar spinal stenosis 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Musculoskeletal chest pain 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Osteoarthritis 2/1054 (0.2%) 2 3/1067 (0.3%) 3 2/879 (0.2%) 2 1/856 (0.1%) 1
    Osteonecrosis 3/1054 (0.3%) 3 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Rhabdomyolysis 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Spinal osteoarthritis 1/1054 (0.1%) 1 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Spondylolisthesis 1/1054 (0.1%) 1 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Tenosynovitis 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Abdominal neoplasm 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Adenocarcinoma of colon 1/1054 (0.1%) 1 2/1067 (0.2%) 2 0/879 (0%) 0 0/856 (0%) 0
    B-cell lymphoma 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Basal cell carcinoma 2/1054 (0.2%) 3 2/1067 (0.2%) 3 0/879 (0%) 0 0/856 (0%) 0
    Benign small intestinal neoplasm 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Bladder cancer 1/1054 (0.1%) 1 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Bladder neoplasm 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Breast cancer 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 2/856 (0.2%) 2
    Breast cancer metastatic 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Cardiac myxoma 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Clear cell renal cell carcinoma 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Colon adenoma 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Colon cancer 1/1054 (0.1%) 1 1/1067 (0.1%) 1 1/879 (0.1%) 1 0/856 (0%) 0
    Endometrial adenocarcinoma 0/599 (0%) 0 1/627 (0.2%) 1 0/501 (0%) 0 0/508 (0%) 0
    Glioblastoma 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Glioblastoma multiforme 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Hepatic neoplasm 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Intraductal proliferative breast lesion 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Invasive ductal breast carcinoma 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Lip squamous cell carcinoma 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Lung adenocarcinoma 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Lung cancer metastatic 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Lung neoplasm malignant 1/1054 (0.1%) 1 2/1067 (0.2%) 2 0/879 (0%) 0 0/856 (0%) 0
    Malignant melanoma 0/1054 (0%) 0 2/1067 (0.2%) 2 0/879 (0%) 0 1/856 (0.1%) 1
    Malignant melanoma in situ 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Metastases to central nervous system 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Metastatic neoplasm 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Oesophageal adenocarcinoma 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Ovarian cancer stage iv 0/599 (0%) 0 1/627 (0.2%) 1 0/501 (0%) 0 0/508 (0%) 0
    Pancreatic neoplasm 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Parathyroid tumour benign 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Plasma cell myeloma 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Prostate cancer 2/455 (0.4%) 2 0/440 (0%) 0 2/378 (0.5%) 2 0/348 (0%) 0
    Prostate cancer metastatic 1/455 (0.2%) 1 1/440 (0.2%) 1 0/378 (0%) 0 1/348 (0.3%) 1
    Rectal adenocarcinoma 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Renal cell carcinoma 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Small cell lung cancer 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Squamous cell carcinoma of the tongue 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Transitional cell cancer of renal pelvis and ureter metastatic 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Transitional cell carcinoma 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Uterine cancer 1/599 (0.2%) 1 0/627 (0%) 0 0/501 (0%) 0 0/508 (0%) 0
    Nervous system disorders
    Altered state of consciousness 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Basal ganglia infarction 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Carotid artery stenosis 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Cerebellar haemorrhage 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Cerebellar infarction 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Cerebral haemorrhage 0/1054 (0%) 0 1/1067 (0.1%) 1 1/879 (0.1%) 1 0/856 (0%) 0
    Cerebral infarction 1/1054 (0.1%) 1 1/1067 (0.1%) 1 3/879 (0.3%) 4 0/856 (0%) 0
    Cerebrovascular accident 0/1054 (0%) 0 5/1067 (0.5%) 7 0/879 (0%) 0 3/856 (0.4%) 3
    Cognitive disorder 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Coma 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Dementia 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 2/856 (0.2%) 2
    Dementia alzheimer's type 1/1054 (0.1%) 1 2/1067 (0.2%) 2 0/879 (0%) 0 4/856 (0.5%) 5
    Dementia of the alzheimer's type, with delirium 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Dizziness 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Embolic stroke 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Encephalopathy 1/1054 (0.1%) 1 2/1067 (0.2%) 2 0/879 (0%) 0 1/856 (0.1%) 1
    Epilepsy 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 2/856 (0.2%) 2
    Generalised tonic-clonic seizure 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Haemorrhage intracranial 1/1054 (0.1%) 1 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Haemorrhagic stroke 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Headache 1/1054 (0.1%) 1 3/1067 (0.3%) 3 0/879 (0%) 0 0/856 (0%) 0
    Hypertensive encephalopathy 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Hypoaesthesia 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Ischaemic stroke 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Lacunar infarction 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Loss of consciousness 2/1054 (0.2%) 2 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Metabolic encephalopathy 1/1054 (0.1%) 1 1/1067 (0.1%) 1 1/879 (0.1%) 1 0/856 (0%) 0
    Presyncope 3/1054 (0.3%) 3 1/1067 (0.1%) 1 0/879 (0%) 0 2/856 (0.2%) 2
    Seizure 0/1054 (0%) 0 4/1067 (0.4%) 4 1/879 (0.1%) 1 1/856 (0.1%) 1
    Somnolence 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Spinal cord compression 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Spinal epidural haematoma 1/1054 (0.1%) 1 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Subarachnoid haemorrhage 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Syncope 8/1054 (0.8%) 11 14/1067 (1.3%) 14 5/879 (0.6%) 5 7/856 (0.8%) 7
    Thalamic infarction 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Thalamus haemorrhage 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Thrombotic cerebral infarction 0/1054 (0%) 0 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Tonic convulsion 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Transient ischaemic attack 2/1054 (0.2%) 2 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Pregnancy, puerperium and perinatal conditions
    Cephalhaematoma 1/1054 (0.1%) 1 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Product Issues
    Device dislocation 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Psychiatric disorders
    Abnormal behaviour 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Affective disorder 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Aggression 0/1054 (0%) 0 2/1067 (0.2%) 2 1/879 (0.1%) 1 2/856 (0.2%) 2
    Agitation 3/1054 (0.3%) 3 2/1067 (0.2%) 2 1/879 (0.1%) 1 1/856 (0.1%) 1
    Anxiety 2/1054 (0.2%) 2 2/1067 (0.2%) 2 0/879 (0%) 0 1/856 (0.1%) 1
    Behavioural and psychiatric symptoms of dementia 0/1054 (0%) 0 1/1067 (0.1%) 1 2/879 (0.2%) 2 0/856 (0%) 0
    Confusional state 3/1054 (0.3%) 3 1/1067 (0.1%) 1 2/879 (0.2%) 2 1/856 (0.1%) 1
    Delirium 1/1054 (0.1%) 1 5/1067 (0.5%) 5 1/879 (0.1%) 1 1/856 (0.1%) 1
    Delusion 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Depression 2/1054 (0.2%) 2 1/1067 (0.1%) 1 1/879 (0.1%) 1 0/856 (0%) 0
    Disorientation 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Hallucination 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Mental status changes 2/1054 (0.2%) 2 4/1067 (0.4%) 4 0/879 (0%) 0 2/856 (0.2%) 3
    Phobia 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Psychotic disorder 0/1054 (0%) 0 2/1067 (0.2%) 2 0/879 (0%) 0 0/856 (0%) 0
    Suicide attempt 2/1054 (0.2%) 2 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 2/1054 (0.2%) 2 3/1067 (0.3%) 3 2/879 (0.2%) 2 3/856 (0.4%) 3
    Nephrolithiasis 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Renal colic 0/1054 (0%) 0 0/1067 (0%) 0 2/879 (0.2%) 2 1/856 (0.1%) 1
    Renal failure 0/1054 (0%) 0 2/1067 (0.2%) 2 0/879 (0%) 0 0/856 (0%) 0
    Urinary bladder polyp 1/1054 (0.1%) 1 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Urinary incontinence 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Urinary retention 1/1054 (0.1%) 1 0/1067 (0%) 0 2/879 (0.2%) 2 0/856 (0%) 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 1/455 (0.2%) 1 1/440 (0.2%) 1 3/378 (0.8%) 3 0/348 (0%) 0
    Prostatitis 1/455 (0.2%) 1 0/440 (0%) 0 0/378 (0%) 0 0/348 (0%) 0
    Vulvar dysplasia 0/599 (0%) 0 1/627 (0.2%) 1 0/501 (0%) 0 0/508 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Asthma 1/1054 (0.1%) 1 1/1067 (0.1%) 1 2/879 (0.2%) 2 1/856 (0.1%) 1
    Chronic obstructive pulmonary disease 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Dyspnoea 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Epistaxis 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Organising pneumonia 0/1054 (0%) 0 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Pharyngeal mass 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Pleural effusion 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Pleurisy 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Pneumonia aspiration 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Pneumothorax 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 1/856 (0.1%) 1
    Pulmonary embolism 4/1054 (0.4%) 4 2/1067 (0.2%) 2 1/879 (0.1%) 1 2/856 (0.2%) 2
    Respiratory arrest 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Sleep apnoea syndrome 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 1/856 (0.1%) 1
    Skin and subcutaneous tissue disorders
    Angioedema 0/1054 (0%) 0 1/1067 (0.1%) 1 1/879 (0.1%) 1 0/856 (0%) 0
    Social circumstances
    Immobilisation prolonged 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Respite care 1/1054 (0.1%) 1 0/1067 (0%) 0 0/879 (0%) 0 0/856 (0%) 0
    Vascular disorders
    Aortic aneurysm 3/1054 (0.3%) 3 0/1067 (0%) 0 2/879 (0.2%) 2 0/856 (0%) 0
    Aortic stenosis 1/1054 (0.1%) 1 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Deep vein thrombosis 1/1054 (0.1%) 1 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Hypertension 1/1054 (0.1%) 1 0/1067 (0%) 0 2/879 (0.2%) 2 0/856 (0%) 0
    Hypertensive crisis 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Hypotension 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 2/856 (0.2%) 2
    Lymphoedema 1/1054 (0.1%) 1 0/1067 (0%) 0 1/879 (0.1%) 1 0/856 (0%) 0
    Orthostatic hypotension 1/1054 (0.1%) 1 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Peripheral arterial occlusive disease 0/1054 (0%) 0 1/1067 (0.1%) 1 0/879 (0%) 0 0/856 (0%) 0
    Other (Not Including 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 536/1054 (50.9%) 530/1067 (49.7%) 255/879 (29%) 260/856 (30.4%)
    Gastrointestinal disorders
    Diarrhoea 76/1054 (7.2%) 86 87/1067 (8.2%) 109 23/879 (2.6%) 24 17/856 (2%) 18
    Nausea 54/1054 (5.1%) 69 46/1067 (4.3%) 63 23/879 (2.6%) 32 15/856 (1.8%) 18
    Infections and infestations
    Nasopharyngitis 89/1054 (8.4%) 114 80/1067 (7.5%) 99 29/879 (3.3%) 31 32/856 (3.7%) 36
    Upper respiratory tract infection 64/1054 (6.1%) 74 54/1067 (5.1%) 61 23/879 (2.6%) 25 21/856 (2.5%) 23
    Urinary tract infection 58/1054 (5.5%) 79 72/1067 (6.7%) 103 38/879 (4.3%) 47 36/856 (4.2%) 46
    Injury, poisoning and procedural complications
    Fall 146/1054 (13.9%) 195 144/1067 (13.5%) 207 67/879 (7.6%) 97 80/856 (9.3%) 109
    Musculoskeletal and connective tissue disorders
    Arthralgia 44/1054 (4.2%) 51 56/1067 (5.2%) 62 21/879 (2.4%) 23 22/856 (2.6%) 22
    Back pain 63/1054 (6%) 70 60/1067 (5.6%) 67 26/879 (3%) 26 23/856 (2.7%) 23
    Nervous system disorders
    Dizziness 61/1054 (5.8%) 66 57/1067 (5.3%) 65 23/879 (2.6%) 24 29/856 (3.4%) 31
    Headache 86/1054 (8.2%) 96 86/1067 (8.1%) 151 28/879 (3.2%) 34 29/856 (3.4%) 42
    Psychiatric disorders
    Anxiety 54/1054 (5.1%) 57 58/1067 (5.4%) 59 15/879 (1.7%) 18 17/856 (2%) 17
    Depression 60/1054 (5.7%) 62 57/1067 (5.3%) 57 18/879 (2%) 18 20/856 (2.3%) 20
    Respiratory, thoracic and mediastinal disorders
    Cough 44/1054 (4.2%) 53 58/1067 (5.4%) 69 25/879 (2.8%) 27 18/856 (2.1%) 22

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    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
    Email
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01900665
    Other Study ID Numbers:
    • 15136
    • H8A-MC-LZAX
    First Posted:
    Jul 16, 2013
    Last Update Posted:
    Oct 9, 2019
    Last Verified:
    Sep 1, 2019