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EXPEDITION EXT: Continued Safety Monitoring of Solanezumab (LY2062430) in Alzheimer's Disease

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Terminated
CT.gov ID
NCT01127633
Collaborator
(none)
1,457
Enrollment
147
Locations
2
Arms
74.1
Duration (Months)
9.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is an open-label extension study in Alzheimer's patients who have completed participation in either solanezumab Clinical Trial H8A-MC-LZAM (NCT00905372) or H8A-MC-LZAN (NCT00904683).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
1457 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Continued Efficacy and Safety Monitoring of Solanezumab, an Anti-Amyloid β Antibody in Patients With Alzheimer's Disease
Study Start Date :
Dec 1, 2010
Actual Primary Completion Date :
Jul 1, 2014
Actual Study Completion Date :
Feb 1, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Solanezumab

Drug: Solanezumab
400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
Other Names:
  • LY2062430

    		•
    Placebo Comparator: Placebo

    Drug: Placebo
    Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80.

    Outcome Measures

    Primary Outcome Measures

    1. Assess the Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) [Baseline through Week 104]

      The number of participants with 1 or more AEs assessed as related to the study drug and is summarized cumulatively. In addition, the number of participants with 1 or more serious AEs is summarized cumulatively. A serious AE is defined as an event that results in death, initial or prolonged hospitalization, is life-threatening, leads to persistent or significant disability/incapacity, is associated with congenital anomaly/birth defect, or is considered significant by the investigator for any other reason. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

    Secondary Outcome Measures

    1. Change From Baseline to 104-week Endpoint in Alzheimer's Disease Assessment Scale - Cognitive 14-Item Scale (ADAS-Cog14) [Baseline, Week 104]

      ADAS-Cog14 is ADAS-Cog11 augmented with delayed free recall, digit cancellation, and maze completion measures. A score of 0 to 10 for delayed free recall and a conversion code of 0 to 5 for digit cancellation and maze completion provide total score ranges for this extended ADAS-Cog14 of 0 to 90. Higher scores indicate greater disease severity. Least Squares (LS) Mean was determined by mixed model repeated measures (MMRM) methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 Mini-Mental State Examination (MMSE) status (mild/moderate), concomitant acetylcholinesterase inhibitors (AChEI)/Memantine use at baseline (yes/no), baseline age and treatment*visit.

    2. Change From Baseline to 104-week Endpoint in Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) [Baseline, Week 104]

      ADCS-ADL is a 23-item inventory developed as a Rater-administered questionnaire answered by the participant's caregiver. It measures performance of 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 was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.

    3. Change From Baseline to 104-week Endpoint in Clinical Dementia Rating - Sum of Boxes (CDR-SB) [Baseline, Week 104]

      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 was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.

    4. Change From Baseline to 104-week Endpoint in Neuropsychiatric Inventory (NPI) [Baseline, Week 104]

      The NPI is a questionnaire administered to caregivers that quantifies behavioral changes in dementia. Each of the 12 behavioral domains the caregiver reports as present are scored for Frequency, scale: 1 (Occasionally) to 4 (Very Frequently), and Severity, scale: 1 (Mild) to 3 (Severe). If the domain is reported by the caregiver as 'Not Affected,' that domain is scored as 0. The individual domain scores are calculated by multiplying the frequency times the severity for each domain. NPI Total Score is calculated by adding the individual domain scores together for all 12 domains, with a scores range from 0 to 144. Lower scores indicated less severity and higher scores indicated a greater severity of neuropsychiatric disturbance. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.

    5. Change From Baseline to 104-week Endpoint in Resource Utilization in Dementia - Lite (RUD-Lite) Caregiver Hours [Baseline, Week 104]

      The RUD-Lite is a caregiver-completed assessment designed to assess the amount of formal and informal resources used by participants and the primary caregiver. It is completed by the caregiver and compiles data on the following resources: length of time the caregiver spends giving care, assisting participants with basic activities of daily living (BADL: eating dressing, grooming, bathing); assisting participants with instrumental activities of daily living (IADLs: shopping, cooking, housekeeping, laundry, transportation, taking medication, managing finances), and providing supervision. Scores range from 0 to 24 hours. Higher values indicate greater resource use. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.

    6. Change From Baseline to 104-week Endpoint in EuroQol 5-Dimensional Health-Related Quality of Life Scale Proxy Version (EQ-5D Proxy) [Baseline, Week 104]

      EQ-5D (proxy version) is a generic, multidimensional, health-related, quality-of-life instrument assessing caregiver's impression of participants overall health state. Profile allows caregivers to rate participant's health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale: 1 (no problem), 2 (some problems), and 3 (major problems). These attribute combinations are converted into a weighted Health-State Index Score according to the United States (US) population-based algorithm. EQ-5D US Population-Based Index Scores range from -0.11 to 1.0. A score of 1.0 indicated perfect health. The Overall Health State Index Score is caregiver-reported using a visual analogue scale marked 0 (worst imaginable health) to 100 (best imaginable health state). LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.

    7. Change From Baseline to 104-week Endpoint in Quality of Life in Alzheimer's Disease (QoL-AD) [Baseline, Week 104]

      The QoL-AD (Caregiver Total Score) is a disease-specific measure of quality of life for an Alzheimer's Disease (AD) population administered to the participant's primary caregiver, who answers on behalf of the participant. The assessment consists of 13 items covering physical health, energy, mood, living situations, memory, family, marriage, friends, chores, fun, money, self and life as a whole. The assessment is scored on a 4-point Likert scale with scores ranging from 1 (poor) to 4 (excellent). QoL-AD Total Score is defined as the sum of the 13 items with a scores range from 13 to 52. Higher scores denote a better quality of life. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.

    8. Change From Baseline to 104-week Endpoint in Mini-Mental State Examination (MMSE) [Baseline, Week 104]

      The MMSE is an instrument used to assess a participant's cognitive function. The instrument is divided into 2 sections. The first section measures orientation, memory, and attention with scores ranging from 0 to 21 (lower scores indicate greater impairment). The second section tests the ability of the participant to name objects, follow verbal and written commands, write a sentence, and copy figures with scores ranging from 0 to 9 (lower scores indicate greater impairment). The range for MMSE Total Score is 0 to 30. Lower scores indicate more impairment. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.

    9. Change From Baseline to 52-week Endpoint in Plasma Amyloid Beta (Aβ) Levels [Baseline, Week 52]

      Concentration of the peptide Aβ 1-40 and Aβ 1-42 in plasma measured by immunoassay. The immunoassays for plasma Aβ 1-40 and Aβ 1-42 peptides were modified to render them tolerant to the presence of Solanezumab which would otherwise interfere with non-modified assays. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.

    10. Change From Baseline to 104-week Endpoint in Volumetric Magnetic Resonance Imaging (vMRI) [Baseline, Week 104]

      The vMRI assessment of right and left hippocampal volume is reported. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.

    11. Change From Baseline to 104-week Endpoint in Alzheimer's Disease Assessment Scale - Cognitive Subscore 11-Item Scale (ADAS-Cog11) [Baseline, Week 104]

      The cognitive subscale of the ADAS (ADAS Cog11) was used as a primary efficacy measure and consists of 11 items assessing areas of function most typically impaired in Alzheimer's disease: orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.

    12. Mean Change From Baseline to Endpoint in Amyloid Imaging Parameters in Subjects With Mild Alzheimer's Disease [Baseline, Week 104]

      Florbetapir PET imaging was used to test for change from baseline. The hypothesis that amyloid burden was reduced in participants between the treatment groups from the feeder studies was tested. The change from baseline to the postbaseline visit of the composite summary standard uptake value ratio of florbetapir F18 was calculated. 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 and to subject-specific white matter.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    55 Years and Older
    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 Alzheimer's Disease

    • Has completed participation in solanezumab Study LZAM or Study LZAN through 80 weeks

    • Must continue to have a reliable caregiver who is in frequent contact with the patient for the entire study

    • Must have good vein access to administer infusions

    • Agrees not to participate in studies of any other investigational compounds for the duration of their participation in Study LZAO

    Exclusion Criteria:

    • Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

    • Meets LZAM or LZAN discontinuation criteria at the end of treatment in LZAM or LZAN study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 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. Phoenix Arizona United States 85006
    2 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. Sun City Arizona United States 85351
    3 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. Tucson Arizona United States 85718
    4 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. Little Rock Arkansas United States 72211
    5 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. Carson California United States 90746
    6 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. Laguna Hills California United States 92653
    7 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. Lomita California United States 90717
    8 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. Los Angeles California United States 90073
    9 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. Oxnard California United States 93030
    10 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. San Diego California United States 92103
    11 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. San Francisco California United States 94109
    12 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. Santa Ana California United States 92705
    13 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. Santa Monica California United States 90404
    14 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. Denver Colorado United States 80239
    15 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. Fairfield Connecticut United States 06824
    16 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. Hamden Connecticut United States 06518
    17 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. New Haven Connecticut United States 06510
    18 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. Norwalk Connecticut United States 06851
    19 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. Newark Delaware United States 19713
    20 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. Washington District of Columbia United States 20057
    21 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. Boca Raton Florida United States 33431
    22 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. Fort Myers Florida United States 33912
    23 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. Hollywood Florida United States 33021
    24 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. Miami Springs Florida United States 33166
    25 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. Miami Florida United States 33137
    26 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. Orange City Florida United States 32763
    27 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. Orlando Florida United States 32806
    28 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. Sunrise Florida United States 33351
    29 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. Tampa Florida United States 33613
    30 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. Atlanta Georgia United States 30341
    31 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. Canton Georgia United States 30114
    32 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. Decatur Georgia United States 30033
    33 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. Indianapolis Indiana United States 46202
    34 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. Lexington Kentucky United States 40503
    35 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. Baltimore Maryland United States 21285
    36 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. Rockville Maryland United States 20852
    37 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. Belmont Massachusetts United States 02478
    38 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. Traverse City Michigan United States 49684
    39 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. Creve Coeur Missouri United States 63141
    40 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. Albuquerque New Mexico United States 87109
    41 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. Albany New York United States 12205
    42 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. Amherst New York United States 14226
    43 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. Brooklyn New York United States 11235
    44 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. Latham New York United States 12210
    45 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. New York New York United States 10032
    46 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. Staten Island New York United States 10312
    47 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. Raleigh North Carolina United States 27607
    48 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. Winston-Salem North Carolina United States 27103
    49 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. Beachwood Ohio United States 44122
    50 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. Toledo Ohio United States 43623
    51 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. Oklahoma City Oklahoma United States 73116
    52 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. Eugene Oregon United States 97401
    53 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. Portland Oregon United States 97210
    54 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. Philadelphia Pennsylvania United States 19104
    55 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. East Providence Rhode Island United States 02914
    56 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. Charleston South Carolina United States 29425
    57 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. Greer South Carolina United States 29650
    58 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. Sioux Falls South Dakota United States 57105
    59 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. Salt Lake City Utah United States 84108
    60 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. Bennington Vermont United States 05201
    61 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. Burlington Vermont United States 05401
    62 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. Norfolk Virginia United States 23502
    63 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. Roanoke Virginia United States 24018
    64 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. Seattle Washington United States 98108
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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:
    NCT01127633
    Other Study ID Numbers:
    • 11935
    • H8A-MC-LZAO
    First Posted:
    May 21, 2010
    Last Update Posted:
    Oct 8, 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 Participants who completed one of the feeder studies (Study LZAM (NCT00905372) or Study LZAN (NCT00904683)) were enrolled in this study.
    Pre-assignment Detail
    Arm/Group Title Placebo Solanezumab
    Arm/Group Description Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80. 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
    Period Title: Overall Study
    STARTED 723 734
    Received at Least 1 Dose of Study Drug 723 734
    COMPLETED 70 61
    NOT COMPLETED 653 673

    Baseline Characteristics

    Arm/Group Title Placebo Solanezumab Total
    Arm/Group Description Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80. 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years. Total of all reporting groups
    Overall Participants 723 734 1457
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    73.10
    (8.004)
    72.96
    (7.766)
    73.03
    (7.883)
    Sex: Female, Male (Count of Participants)
    Female
    406
    56.2%
    415
    56.5%
    821
    56.3%
    Male
    317
    43.8%
    319
    43.5%
    636
    43.7%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    137
    18.9%
    149
    20.3%
    286
    19.6%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    13
    1.8%
    16
    2.2%
    29
    2%
    White
    571
    79%
    566
    77.1%
    1137
    78%
    More than one race
    2
    0.3%
    3
    0.4%
    5
    0.3%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    Argentina
    41
    5.7%
    40
    5.4%
    81
    5.6%
    United States
    264
    36.5%
    243
    33.1%
    507
    34.8%
    Japan
    69
    9.5%
    87
    11.9%
    156
    10.7%
    United Kingdom
    17
    2.4%
    18
    2.5%
    35
    2.4%
    Spain
    15
    2.1%
    22
    3%
    37
    2.5%
    Russia
    13
    1.8%
    15
    2%
    28
    1.9%
    Canada
    38
    5.3%
    40
    5.4%
    78
    5.4%
    South Korea
    33
    4.6%
    32
    4.4%
    65
    4.5%
    Sweden
    21
    2.9%
    15
    2%
    36
    2.5%
    Taiwan
    26
    3.6%
    23
    3.1%
    49
    3.4%
    Poland
    18
    2.5%
    25
    3.4%
    43
    3%
    Brazil
    38
    5.3%
    34
    4.6%
    72
    4.9%
    Italy
    41
    5.7%
    45
    6.1%
    86
    5.9%
    Australia
    30
    4.1%
    30
    4.1%
    60
    4.1%
    France
    22
    3%
    23
    3.1%
    45
    3.1%
    Germany
    37
    5.1%
    42
    5.7%
    79
    5.4%

    Outcome Measures

    1. Primary Outcome
    Title Assess the Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs)
    Description The number of participants with 1 or more AEs assessed as related to the study drug and is summarized cumulatively. In addition, the number of participants with 1 or more serious AEs is summarized cumulatively. A serious AE is defined as an event that results in death, initial or prolonged hospitalization, is life-threatening, leads to persistent or significant disability/incapacity, is associated with congenital anomaly/birth defect, or is considered significant by the investigator for any other reason. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
    Time Frame Baseline through Week 104

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least one dose of study drug.
    Arm/Group Title Placebo Solanezumab
    Arm/Group Description Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80. 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
    Measure Participants 723 734
    SAE
    308
    42.6%
    299
    40.7%
    Other AE
    485
    67.1%
    514
    70%
    2. Secondary Outcome
    Title Change From Baseline to 104-week Endpoint in Alzheimer's Disease Assessment Scale - Cognitive 14-Item Scale (ADAS-Cog14)
    Description ADAS-Cog14 is ADAS-Cog11 augmented with delayed free recall, digit cancellation, and maze completion measures. A score of 0 to 10 for delayed free recall and a conversion code of 0 to 5 for digit cancellation and maze completion provide total score ranges for this extended ADAS-Cog14 of 0 to 90. Higher scores indicate greater disease severity. Least Squares (LS) Mean was determined by mixed model repeated measures (MMRM) methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 Mini-Mental State Examination (MMSE) status (mild/moderate), concomitant acetylcholinesterase inhibitors (AChEI)/Memantine use at baseline (yes/no), baseline age and treatment*visit.
    Time Frame Baseline, Week 104

    Outcome Measure Data

    Analysis Population Description
    Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for ADAS-Cog14.
    Arm/Group Title Placebo Solanezumab
    Arm/Group Description Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80. 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
    Measure Participants 409 451
    Least Squares Mean (Standard Error) [Units on a scale]
    17.58
    (0.532)
    17.56
    (0.517)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Solanezumab
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence (legacy)
    Comments The noninferiority margin for this hypothesis was specified as 50% of the treatment difference observed at the end of the feeder study. If the lower limit of the confidence interval (CI) was greater than 0, the noninferiority criterion was met, indicating that at least 50% of the treatment difference observed at the end of the feeder studies was maintained at specified time points in the delayed-start period.
    Statistical Test of Hypothesis p-Value 0.974
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Median Difference (Net)
    Estimated Value -0.02
    Confidence Interval (2-Sided) 95%
    -1.14 to 1.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Change From Baseline to 104-week Endpoint in Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL)
    Description ADCS-ADL is a 23-item inventory developed as a Rater-administered questionnaire answered by the participant's caregiver. It measures performance of 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 was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.
    Time Frame Baseline, Week 104

    Outcome Measure Data

    Analysis Population Description
    Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for ADCS-ADL.
    Arm/Group Title Placebo Solanezumab
    Arm/Group Description Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80. 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
    Measure Participants 420 456
    Least Squares Mean (Standard Error) [Units on a scale]
    -26.77
    (0.888)
    -24.77
    (0.871)
    4. Secondary Outcome
    Title Change From Baseline to 104-week Endpoint 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 was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.
    Time Frame Baseline, Week 104

    Outcome Measure Data

    Analysis Population Description
    Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for CDR-SB.
    Arm/Group Title Placebo Solanezumab
    Arm/Group Description Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80. 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
    Measure Participants 416 452
    Least Squares Mean (Standard Error) [Units on a scale]
    5.59
    (0.174)
    5.27
    (0.169)
    5. Secondary Outcome
    Title Change From Baseline to 104-week Endpoint in Neuropsychiatric Inventory (NPI)
    Description The NPI is a questionnaire administered to caregivers that quantifies behavioral changes in dementia. Each of the 12 behavioral domains the caregiver reports as present are scored for Frequency, scale: 1 (Occasionally) to 4 (Very Frequently), and Severity, scale: 1 (Mild) to 3 (Severe). If the domain is reported by the caregiver as 'Not Affected,' that domain is scored as 0. The individual domain scores are calculated by multiplying the frequency times the severity for each domain. NPI Total Score is calculated by adding the individual domain scores together for all 12 domains, with a scores range from 0 to 144. Lower scores indicated less severity and higher scores indicated a greater severity of neuropsychiatric disturbance. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.
    Time Frame Baseline, Week 104

    Outcome Measure Data

    Analysis Population Description
    Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for NPI.
    Arm/Group Title Placebo Solanezumab
    Arm/Group Description Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80. 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
    Measure Participants 414 457
    Mild Alzheimer's Disease
    4.49
    (0.788)
    5.41
    (0.773)
    Moderate Alzheimer's Disease
    11.90
    (1.517)
    8.10
    (1.427)
    6. Secondary Outcome
    Title Change From Baseline to 104-week Endpoint in Resource Utilization in Dementia - Lite (RUD-Lite) Caregiver Hours
    Description The RUD-Lite is a caregiver-completed assessment designed to assess the amount of formal and informal resources used by participants and the primary caregiver. It is completed by the caregiver and compiles data on the following resources: length of time the caregiver spends giving care, assisting participants with basic activities of daily living (BADL: eating dressing, grooming, bathing); assisting participants with instrumental activities of daily living (IADLs: shopping, cooking, housekeeping, laundry, transportation, taking medication, managing finances), and providing supervision. Scores range from 0 to 24 hours. Higher values indicate greater resource use. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.
    Time Frame Baseline, Week 104

    Outcome Measure Data

    Analysis Population Description
    Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for RUD-Lite.
    Arm/Group Title Placebo Solanezumab
    Arm/Group Description Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80. 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
    Measure Participants 415 451
    Mild Alzheimer's Disease-Basic ADL
    1.96
    (0.184)
    1.21
    (0.182)
    Mild Alzheimer's Disease-Instrumental ADL
    1.65
    (0.207)
    1.05
    (0.205)
    Mild Alzheimer's Disease-Supervision
    2.84
    (0.368)
    2.59
    (0.361)
    Moderate Alzheimer's Disease-Basic ADL
    3.19
    (0.461)
    3.54
    (0.436)
    Moderate Alzheimer's Disease-Instrumental ADL
    1.75
    (0.461)
    1.72
    (0.433)
    Moderate Alzheimer's Disease-Supervision
    5.03
    (0.693)
    4.47
    (0.654)
    7. Secondary Outcome
    Title Change From Baseline to 104-week Endpoint in EuroQol 5-Dimensional Health-Related Quality of Life Scale Proxy Version (EQ-5D Proxy)
    Description EQ-5D (proxy version) is a generic, multidimensional, health-related, quality-of-life instrument assessing caregiver's impression of participants overall health state. Profile allows caregivers to rate participant's health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale: 1 (no problem), 2 (some problems), and 3 (major problems). These attribute combinations are converted into a weighted Health-State Index Score according to the United States (US) population-based algorithm. EQ-5D US Population-Based Index Scores range from -0.11 to 1.0. A score of 1.0 indicated perfect health. The Overall Health State Index Score is caregiver-reported using a visual analogue scale marked 0 (worst imaginable health) to 100 (best imaginable health state). LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.
    Time Frame Baseline, Week 104

    Outcome Measure Data

    Analysis Population Description
    Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for EQ-5D Proxy.
    Arm/Group Title Placebo Solanezumab
    Arm/Group Description Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80. 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
    Measure Participants 414 453
    Mild Alzheimer's Disease
    -0.07
    (0.010)
    -0.06
    (0.009)
    Moderate Alzheimer's Disease
    -0.16
    (0.020)
    -0.16
    (0.019)
    8. Secondary Outcome
    Title Change From Baseline to 104-week Endpoint in Quality of Life in Alzheimer's Disease (QoL-AD)
    Description The QoL-AD (Caregiver Total Score) is a disease-specific measure of quality of life for an Alzheimer's Disease (AD) population administered to the participant's primary caregiver, who answers on behalf of the participant. The assessment consists of 13 items covering physical health, energy, mood, living situations, memory, family, marriage, friends, chores, fun, money, self and life as a whole. The assessment is scored on a 4-point Likert scale with scores ranging from 1 (poor) to 4 (excellent). QoL-AD Total Score is defined as the sum of the 13 items with a scores range from 13 to 52. Higher scores denote a better quality of life. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.
    Time Frame Baseline, Week 104

    Outcome Measure Data

    Analysis Population Description
    Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for QoL-AD.
    Arm/Group Title Placebo Solanezumab
    Arm/Group Description Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80. 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
    Measure Participants 387 413
    QLAD Self-Report Total Score-Mild Alzheimer's
    -1.37
    (0.331)
    -0.98
    (0.327)
    QLAD Caregiver Total Score-Mild Alzheimer's
    -3.28
    (0.350)
    -3.63
    (0.345)
    QLAD Self-Report Total Score-Moderate Alzheimer's
    -2.52
    (0.605)
    -2.34
    (0.585)
    QLAD Caregiver Total Score-Moderate Alzheimer's
    -4.26
    (0.573)
    -3.14
    (0.552)
    9. Secondary Outcome
    Title Change From Baseline to 104-week Endpoint in Mini-Mental State Examination (MMSE)
    Description The MMSE is an instrument used to assess a participant's cognitive function. The instrument is divided into 2 sections. The first section measures orientation, memory, and attention with scores ranging from 0 to 21 (lower scores indicate greater impairment). The second section tests the ability of the participant to name objects, follow verbal and written commands, write a sentence, and copy figures with scores ranging from 0 to 9 (lower scores indicate greater impairment). The range for MMSE Total Score is 0 to 30. Lower scores indicate more impairment. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.
    Time Frame Baseline, Week 104

    Outcome Measure Data

    Analysis Population Description
    Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for MMSE.
    Arm/Group Title Placebo Solanezumab
    Arm/Group Description Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80. 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
    Measure Participants 412 446
    Least Squares Mean (Standard Error) [Units on a scale]
    -8.08
    (0.270)
    -7.60
    (0.263)
    10. Secondary Outcome
    Title Change From Baseline to 52-week Endpoint in Plasma Amyloid Beta (Aβ) Levels
    Description Concentration of the peptide Aβ 1-40 and Aβ 1-42 in plasma measured by immunoassay. The immunoassays for plasma Aβ 1-40 and Aβ 1-42 peptides were modified to render them tolerant to the presence of Solanezumab which would otherwise interfere with non-modified assays. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.
    Time Frame Baseline, Week 52

    Outcome Measure Data

    Analysis Population Description
    All Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for plasma Aβ 1-40 and Aβ 1-42.
    Arm/Group Title Placebo Solanezumab
    Arm/Group Description Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80. 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
    Measure Participants 515 532
    Aβ 1-40-Mild Alzheimer's Disease
    176412.04
    (3718.292)
    173064.99
    (3717.695)
    Aβ 1-42-Mild Alzheimer's Disease
    19854.92
    (366.392)
    19723.48
    (368.644)
    Aβ 1-40-Moderate Alzheimer's Disease
    169356
    (4627.8)
    169087
    (4511.6)
    Aβ 1-42-Moderate Alzheimer's Disease
    19237
    (556.3)
    19552
    (528.7)
    11. Secondary Outcome
    Title Change From Baseline to 104-week Endpoint in Volumetric Magnetic Resonance Imaging (vMRI)
    Description The vMRI assessment of right and left hippocampal volume is reported. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.
    Time Frame Baseline, Week 104

    Outcome Measure Data

    Analysis Population Description
    Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for vMRI.
    Arm/Group Title Placebo Solanezumab
    Arm/Group Description Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80. 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
    Measure Participants 310 325
    Right hippocampal volume-Mild Alzheimer's Disease
    -230.23
    (8.232)
    -230.07
    (8.195)
    Left hippocampal volume-Mild Alzheimer's Disease
    -257.15
    (8.153)
    -244.00
    (8.115)
    Right hippocampal volume-Moderate Alzheimer's
    -261.39
    (11.796)
    -256.52
    (11.246)
    Left hippocampal volume-Moderate Alzheimer's
    -255.16
    (11.466)
    -253.29
    (10.858)
    12. Secondary Outcome
    Title Change From Baseline to 104-week Endpoint in Alzheimer's Disease Assessment Scale - Cognitive Subscore 11-Item Scale (ADAS-Cog11)
    Description The cognitive subscale of the ADAS (ADAS Cog11) was used as a primary efficacy measure and consists of 11 items assessing areas of function most typically impaired in Alzheimer's disease: orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit.
    Time Frame Baseline, Week 104

    Outcome Measure Data

    Analysis Population Description
    Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for ADAS-Cog11.
    Arm/Group Title Placebo Solanezumab
    Arm/Group Description Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80. 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
    Measure Participants 375 409
    Least Squares Mean (Standard Error) [units on a scale]
    17.78
    (0.595)
    17.38
    (0.580)
    13. Secondary Outcome
    Title Mean Change From Baseline to Endpoint in Amyloid Imaging Parameters in Subjects With Mild Alzheimer's Disease
    Description Florbetapir PET imaging was used to test for change from baseline. The hypothesis that amyloid burden was reduced in participants between the treatment groups from the feeder studies was tested. The change from baseline to the postbaseline visit of the composite summary standard uptake value ratio of florbetapir F18 was calculated. 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 and to subject-specific white matter.
    Time Frame Baseline, Week 104

    Outcome Measure Data

    Analysis Population Description
    Feeder Intent-to-Treat Population: All randomized participants with mild Alzheimer's Disease from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for Amyloid Plaque Burden.
    Arm/Group Title Placebo Solanezumab
    Arm/Group Description Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80. 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
    Measure Participants 42 48
    Mean (Standard Deviation) [Standard Uptake Value ratio (SUVr)]
    0.00
    (0.131)
    -0.01
    (0.222)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
    Arm/Group Title Placebo Solanezumab
    Arm/Group Description Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80. 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
    All Cause Mortality
    Placebo Solanezumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Placebo Solanezumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 308/723 (42.6%) 299/734 (40.7%)
    Blood and lymphatic system disorders
    Anaemia 3/723 (0.4%) 3 2/734 (0.3%) 2
    Anaemia folate deficiency 1/723 (0.1%) 1 0/734 (0%) 0
    Coagulopathy 1/723 (0.1%) 1 0/734 (0%) 0
    Normochromic normocytic anaemia 1/723 (0.1%) 1 0/734 (0%) 0
    Cardiac disorders
    Acute myocardial infarction 4/723 (0.6%) 4 4/734 (0.5%) 5
    Angina pectoris 2/723 (0.3%) 2 4/734 (0.5%) 5
    Arrhythmia supraventricular 1/723 (0.1%) 1 0/734 (0%) 0
    Atrial fibrillation 5/723 (0.7%) 5 9/734 (1.2%) 9
    Atrial flutter 0/723 (0%) 0 1/734 (0.1%) 1
    Atrioventricular block 2/723 (0.3%) 2 2/734 (0.3%) 2
    Atrioventricular block second degree 1/723 (0.1%) 1 1/734 (0.1%) 1
    Bradycardia 1/723 (0.1%) 3 2/734 (0.3%) 2
    Cardiac arrest 5/723 (0.7%) 5 5/734 (0.7%) 5
    Cardiac failure 2/723 (0.3%) 2 3/734 (0.4%) 3
    Cardiac failure acute 0/723 (0%) 0 2/734 (0.3%) 2
    Cardiac failure congestive 6/723 (0.8%) 6 5/734 (0.7%) 5
    Cardiac perforation 1/723 (0.1%) 1 0/734 (0%) 0
    Cardio-respiratory arrest 2/723 (0.3%) 2 2/734 (0.3%) 2
    Cardiogenic shock 0/723 (0%) 0 1/734 (0.1%) 1
    Cardiomyopathy 1/723 (0.1%) 1 1/734 (0.1%) 1
    Cardiopulmonary failure 1/723 (0.1%) 1 0/734 (0%) 0
    Cardiovascular disorder 0/723 (0%) 0 1/734 (0.1%) 1
    Coronary artery stenosis 1/723 (0.1%) 1 0/734 (0%) 0
    Myocardial infarction 5/723 (0.7%) 5 4/734 (0.5%) 4
    Palpitations 1/723 (0.1%) 1 0/734 (0%) 0
    Pericardial effusion 0/723 (0%) 0 1/734 (0.1%) 1
    Sinus bradycardia 0/723 (0%) 0 1/734 (0.1%) 1
    Sinus node dysfunction 4/723 (0.6%) 4 1/734 (0.1%) 1
    Tachycardia 1/723 (0.1%) 1 0/734 (0%) 0
    Ventricular extrasystoles 0/723 (0%) 0 1/734 (0.1%) 1
    Ear and labyrinth disorders
    Vertigo 0/723 (0%) 0 1/734 (0.1%) 1
    Endocrine disorders
    Myxoedema 0/723 (0%) 0 1/734 (0.1%) 1
    Eye disorders
    Cataract 3/723 (0.4%) 3 2/734 (0.3%) 3
    Glaucoma 0/723 (0%) 0 1/734 (0.1%) 1
    Retinal detachment 0/723 (0%) 0 1/734 (0.1%) 1
    Strabismus 1/723 (0.1%) 1 0/734 (0%) 0
    Vitreous haemorrhage 0/723 (0%) 0 1/734 (0.1%) 1
    Gastrointestinal disorders
    Abdominal hernia 0/723 (0%) 0 1/734 (0.1%) 1
    Abdominal pain 3/723 (0.4%) 3 0/734 (0%) 0
    Abdominal pain upper 1/723 (0.1%) 1 0/734 (0%) 0
    Colitis ischaemic 0/723 (0%) 0 1/734 (0.1%) 1
    Colonic fistula 1/723 (0.1%) 1 0/734 (0%) 0
    Colonic pseudo-obstruction 1/723 (0.1%) 1 0/734 (0%) 0
    Constipation 1/723 (0.1%) 1 0/734 (0%) 0
    Diarrhoea 4/723 (0.6%) 4 0/734 (0%) 0
    Diarrhoea haemorrhagic 1/723 (0.1%) 1 0/734 (0%) 0
    Diverticular fistula 1/723 (0.1%) 1 0/734 (0%) 0
    Diverticulum 1/723 (0.1%) 1 0/734 (0%) 0
    Duodenal ulcer 0/723 (0%) 0 2/734 (0.3%) 2
    Dyspepsia 1/723 (0.1%) 1 0/734 (0%) 0
    Dysphagia 0/723 (0%) 0 1/734 (0.1%) 1
    Erosive oesophagitis 1/723 (0.1%) 1 0/734 (0%) 0
    Faecaloma 1/723 (0.1%) 1 3/734 (0.4%) 3
    Gastric ulcer 0/723 (0%) 0 1/734 (0.1%) 1
    Gastric ulcer haemorrhage 1/723 (0.1%) 1 1/734 (0.1%) 1
    Gastritis 0/723 (0%) 0 2/734 (0.3%) 2
    Gastrointestinal haemorrhage 1/723 (0.1%) 1 1/734 (0.1%) 1
    Gastrooesophageal reflux disease 1/723 (0.1%) 1 1/734 (0.1%) 1
    Haematochezia 0/723 (0%) 0 2/734 (0.3%) 2
    Haemorrhoids 0/723 (0%) 0 1/734 (0.1%) 1
    Hiatus hernia 0/723 (0%) 0 1/734 (0.1%) 1
    Ileus 1/723 (0.1%) 1 0/734 (0%) 0
    Ileus paralytic 2/723 (0.3%) 2 0/734 (0%) 0
    Inguinal hernia 2/723 (0.3%) 2 4/734 (0.5%) 4
    Intestinal obstruction 1/723 (0.1%) 1 3/734 (0.4%) 3
    Jejunal perforation 1/723 (0.1%) 1 0/734 (0%) 0
    Large intestine polyp 1/723 (0.1%) 1 0/734 (0%) 0
    Lower gastrointestinal haemorrhage 1/723 (0.1%) 1 0/734 (0%) 0
    Oesophageal perforation 0/723 (0%) 0 1/734 (0.1%) 1
    Oesophageal ulcer haemorrhage 1/723 (0.1%) 1 0/734 (0%) 0
    Pancreatitis 5/723 (0.7%) 5 3/734 (0.4%) 3
    Pancreatitis acute 0/723 (0%) 0 2/734 (0.3%) 2
    Peptic ulcer 0/723 (0%) 0 1/734 (0.1%) 1
    Rectal prolapse 0/723 (0%) 0 1/734 (0.1%) 1
    Rectal ulcer haemorrhage 0/723 (0%) 0 1/734 (0.1%) 1
    Small intestinal obstruction 3/723 (0.4%) 5 1/734 (0.1%) 1
    Small intestinal perforation 0/723 (0%) 0 1/734 (0.1%) 1
    Subileus 1/723 (0.1%) 1 0/734 (0%) 0
    Upper gastrointestinal haemorrhage 2/723 (0.3%) 2 3/734 (0.4%) 3
    Vomiting 2/723 (0.3%) 2 1/734 (0.1%) 1
    General disorders
    Abasia 0/723 (0%) 0 1/734 (0.1%) 1
    Adverse drug reaction 1/723 (0.1%) 1 0/734 (0%) 0
    Asthenia 5/723 (0.7%) 5 2/734 (0.3%) 2
    Catheter site haemorrhage 0/723 (0%) 0 1/734 (0.1%) 1
    Chest pain 2/723 (0.3%) 2 1/734 (0.1%) 1
    Complication associated with device 2/723 (0.3%) 2 0/734 (0%) 0
    Death 4/723 (0.6%) 4 1/734 (0.1%) 1
    Drowning 0/723 (0%) 0 1/734 (0.1%) 1
    Gait disturbance 0/723 (0%) 0 1/734 (0.1%) 1
    General physical health deterioration 2/723 (0.3%) 2 0/734 (0%) 0
    Non-cardiac chest pain 2/723 (0.3%) 2 1/734 (0.1%) 1
    Oedema peripheral 1/723 (0.1%) 1 1/734 (0.1%) 1
    Pain 1/723 (0.1%) 1 0/734 (0%) 0
    Pyrexia 1/723 (0.1%) 1 3/734 (0.4%) 3
    Sudden death 3/723 (0.4%) 3 1/734 (0.1%) 1
    Hepatobiliary disorders
    Bile duct obstruction 1/723 (0.1%) 1 0/734 (0%) 0
    Bile duct stone 1/723 (0.1%) 1 1/734 (0.1%) 1
    Cholangitis 1/723 (0.1%) 1 1/734 (0.1%) 1
    Cholecystitis 2/723 (0.3%) 2 0/734 (0%) 0
    Cholecystitis acute 2/723 (0.3%) 2 2/734 (0.3%) 3
    Cholelithiasis 2/723 (0.3%) 2 1/734 (0.1%) 1
    Drug-induced liver injury 0/723 (0%) 0 1/734 (0.1%) 1
    Gallbladder polyp 1/723 (0.1%) 1 0/734 (0%) 0
    Hepatic steatosis 1/723 (0.1%) 1 0/734 (0%) 0
    Infections and infestations
    Abdominal abscess 0/723 (0%) 0 1/734 (0.1%) 1
    Appendicitis 0/723 (0%) 0 2/734 (0.3%) 2
    Arthritis bacterial 0/723 (0%) 0 1/734 (0.1%) 1
    Bacteraemia 0/723 (0%) 0 1/734 (0.1%) 1
    Bacterial infection 1/723 (0.1%) 1 0/734 (0%) 0
    Bronchitis 0/723 (0%) 0 5/734 (0.7%) 5
    Campylobacter gastroenteritis 0/723 (0%) 0 1/734 (0.1%) 1
    Cellulitis 1/723 (0.1%) 1 7/734 (1%) 8
    Clostridium difficile colitis 2/723 (0.3%) 3 1/734 (0.1%) 1
    Clostridium difficile infection 1/723 (0.1%) 1 1/734 (0.1%) 1
    Colostomy infection 1/723 (0.1%) 1 0/734 (0%) 0
    Cystitis 0/723 (0%) 0 2/734 (0.3%) 2
    Device related infection 1/723 (0.1%) 1 0/734 (0%) 0
    Diverticulitis 4/723 (0.6%) 4 3/734 (0.4%) 3
    Erysipelas 0/723 (0%) 0 1/734 (0.1%) 1
    Escherichia sepsis 1/723 (0.1%) 1 0/734 (0%) 0
    Escherichia urinary tract infection 0/723 (0%) 0 1/734 (0.1%) 1
    Extradural abscess 1/723 (0.1%) 1 0/734 (0%) 0
    Gastroenteritis 1/723 (0.1%) 1 1/734 (0.1%) 1
    Gastroenteritis viral 0/723 (0%) 0 3/734 (0.4%) 3
    Groin abscess 1/723 (0.1%) 1 0/734 (0%) 0
    Herpes simplex encephalitis 1/723 (0.1%) 1 0/734 (0%) 0
    Herpes zoster 1/723 (0.1%) 1 1/734 (0.1%) 1
    Infected skin ulcer 0/723 (0%) 0 1/734 (0.1%) 1
    Influenza 2/723 (0.3%) 2 4/734 (0.5%) 4
    Labyrinthitis 1/723 (0.1%) 1 0/734 (0%) 0
    Lower respiratory tract infection 1/723 (0.1%) 1 1/734 (0.1%) 1
    Lung infection 0/723 (0%) 0 1/734 (0.1%) 1
    Mediastinitis 0/723 (0%) 0 1/734 (0.1%) 1
    Meningitis bacterial 1/723 (0.1%) 1 0/734 (0%) 0
    Orchitis 0/317 (0%) 0 1/319 (0.3%) 1
    Pericarditis tuberculous 0/723 (0%) 0 1/734 (0.1%) 1
    Pharyngitis 1/723 (0.1%) 1 0/734 (0%) 0
    Pneumonia 27/723 (3.7%) 31 27/734 (3.7%) 31
    Pneumonia bacterial 0/723 (0%) 0 1/734 (0.1%) 1
    Pneumonia pneumococcal 1/723 (0.1%) 1 1/734 (0.1%) 1
    Post procedural infection 0/723 (0%) 0 1/734 (0.1%) 1
    Postoperative wound infection 1/723 (0.1%) 1 0/734 (0%) 0
    Pulmonary sepsis 3/723 (0.4%) 3 0/734 (0%) 0
    Pulmonary tuberculosis 0/723 (0%) 0 1/734 (0.1%) 1
    Respiratory tract infection 0/723 (0%) 0 1/734 (0.1%) 1
    Sepsis 3/723 (0.4%) 4 6/734 (0.8%) 6
    Septic shock 2/723 (0.3%) 2 1/734 (0.1%) 1
    Sinusitis 1/723 (0.1%) 1 1/734 (0.1%) 1
    Tooth abscess 0/723 (0%) 0 1/734 (0.1%) 1
    Upper respiratory tract infection 0/723 (0%) 0 2/734 (0.3%) 2
    Urinary tract infection 16/723 (2.2%) 21 17/734 (2.3%) 19
    Urinary tract infection bacterial 0/723 (0%) 0 1/734 (0.1%) 1
    Urinary tract infection staphylococcal 1/723 (0.1%) 1 0/734 (0%) 0
    Urosepsis 3/723 (0.4%) 4 5/734 (0.7%) 7
    Viral infection 1/723 (0.1%) 1 0/734 (0%) 0
    Wound infection 1/723 (0.1%) 1 0/734 (0%) 0
    Injury, poisoning and procedural complications
    Acetabulum fracture 0/723 (0%) 0 1/734 (0.1%) 1
    Ankle fracture 1/723 (0.1%) 1 0/734 (0%) 0
    Bone contusion 0/723 (0%) 0 1/734 (0.1%) 1
    Cervical vertebral fracture 2/723 (0.3%) 2 2/734 (0.3%) 3
    Clavicle fracture 0/723 (0%) 0 1/734 (0.1%) 1
    Concussion 3/723 (0.4%) 3 1/734 (0.1%) 1
    Contusion 1/723 (0.1%) 1 1/734 (0.1%) 1
    Craniocerebral injury 1/723 (0.1%) 1 0/734 (0%) 0
    Facial bones fracture 1/723 (0.1%) 1 1/734 (0.1%) 1
    Fall 27/723 (3.7%) 27 23/734 (3.1%) 25
    Femoral neck fracture 4/723 (0.6%) 4 13/734 (1.8%) 13
    Femur fracture 11/723 (1.5%) 11 3/734 (0.4%) 3
    Fibula fracture 1/723 (0.1%) 1 0/734 (0%) 0
    Flail chest 1/723 (0.1%) 1 0/734 (0%) 0
    Foot fracture 0/723 (0%) 0 1/734 (0.1%) 1
    Forearm fracture 0/723 (0%) 0 1/734 (0.1%) 1
    Fractured ischium 0/723 (0%) 0 1/734 (0.1%) 1
    Head injury 2/723 (0.3%) 2 2/734 (0.3%) 2
    Hip fracture 8/723 (1.1%) 8 11/734 (1.5%) 12
    Humerus fracture 4/723 (0.6%) 4 1/734 (0.1%) 1
    Incisional hernia 1/723 (0.1%) 1 0/734 (0%) 0
    Injury 1/723 (0.1%) 1 0/734 (0%) 0
    Joint dislocation 1/723 (0.1%) 1 0/734 (0%) 0
    Joint injury 1/723 (0.1%) 1 0/734 (0%) 0
    Laceration 3/723 (0.4%) 3 0/734 (0%) 0
    Ligament sprain 0/723 (0%) 0 1/734 (0.1%) 1
    Lumbar vertebral fracture 1/723 (0.1%) 1 0/734 (0%) 0
    Patella fracture 2/723 (0.3%) 2 1/734 (0.1%) 1
    Pelvic fracture 0/723 (0%) 0 4/734 (0.5%) 4
    Periprosthetic fracture 0/723 (0%) 0 1/734 (0.1%) 1
    Pubis fracture 1/723 (0.1%) 1 0/734 (0%) 0
    Pulmonary contusion 1/723 (0.1%) 1 0/734 (0%) 0
    Radius fracture 2/723 (0.3%) 2 2/734 (0.3%) 2
    Rib fracture 3/723 (0.4%) 3 0/734 (0%) 0
    Road traffic accident 0/723 (0%) 0 1/734 (0.1%) 1
    Skull fracture 1/723 (0.1%) 1 0/734 (0%) 0
    Spinal column injury 1/723 (0.1%) 1 0/734 (0%) 0
    Spinal compression fracture 1/723 (0.1%) 1 2/734 (0.3%) 2
    Spinal fracture 1/723 (0.1%) 1 1/734 (0.1%) 1
    Subdural haematoma 4/723 (0.6%) 4 5/734 (0.7%) 5
    Subdural haemorrhage 1/723 (0.1%) 1 1/734 (0.1%) 1
    Tibia fracture 1/723 (0.1%) 1 0/734 (0%) 0
    Traumatic haematoma 0/723 (0%) 0 1/734 (0.1%) 1
    Traumatic intracranial haemorrhage 0/723 (0%) 0 1/734 (0.1%) 1
    Upper limb fracture 2/723 (0.3%) 2 1/734 (0.1%) 1
    Wound 0/723 (0%) 0 1/734 (0.1%) 1
    Wound dehiscence 0/723 (0%) 0 1/734 (0.1%) 1
    Wrist fracture 0/723 (0%) 0 2/734 (0.3%) 2
    Investigations
    Blood pressure increased 1/723 (0.1%) 3 0/734 (0%) 0
    Hepatic enzyme increased 1/723 (0.1%) 1 0/734 (0%) 0
    Metabolism and nutrition disorders
    Adult failure to thrive 0/723 (0%) 0 1/734 (0.1%) 1
    Decreased appetite 3/723 (0.4%) 3 2/734 (0.3%) 2
    Dehydration 7/723 (1%) 7 13/734 (1.8%) 15
    Diabetes mellitus 0/723 (0%) 0 1/734 (0.1%) 1
    Failure to thrive 1/723 (0.1%) 1 1/734 (0.1%) 1
    Gout 0/723 (0%) 0 1/734 (0.1%) 1
    Hyperammonaemia 1/723 (0.1%) 1 0/734 (0%) 0
    Hyperglycaemia 0/723 (0%) 0 1/734 (0.1%) 1
    Hyperkalaemia 1/723 (0.1%) 1 0/734 (0%) 0
    Hypernatraemia 1/723 (0.1%) 1 0/734 (0%) 0
    Hyperosmolar hyperglycaemic state 1/723 (0.1%) 1 0/734 (0%) 0
    Hypoglycaemia 4/723 (0.6%) 4 0/734 (0%) 0
    Hyponatraemia 0/723 (0%) 0 1/734 (0.1%) 1
    Hypophagia 1/723 (0.1%) 1 1/734 (0.1%) 2
    Malnutrition 1/723 (0.1%) 1 2/734 (0.3%) 2
    Type 2 diabetes mellitus 0/723 (0%) 0 1/734 (0.1%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/723 (0.1%) 1 1/734 (0.1%) 1
    Arthritis 2/723 (0.3%) 2 0/734 (0%) 0
    Arthropathy 0/723 (0%) 0 1/734 (0.1%) 1
    Back pain 2/723 (0.3%) 2 2/734 (0.3%) 2
    Cervical spinal stenosis 1/723 (0.1%) 1 0/734 (0%) 0
    Dupuytren's contracture 0/723 (0%) 0 1/734 (0.1%) 1
    Foot deformity 0/723 (0%) 0 1/734 (0.1%) 1
    Gouty arthritis 2/723 (0.3%) 2 0/734 (0%) 0
    Intervertebral disc protrusion 1/723 (0.1%) 1 1/734 (0.1%) 1
    Joint effusion 0/723 (0%) 0 1/734 (0.1%) 1
    Joint swelling 0/723 (0%) 0 1/734 (0.1%) 1
    Lumbar spinal stenosis 1/723 (0.1%) 1 0/734 (0%) 0
    Muscle spasms 0/723 (0%) 0 1/734 (0.1%) 1
    Muscular weakness 0/723 (0%) 0 1/734 (0.1%) 1
    Osteoarthritis 7/723 (1%) 7 13/734 (1.8%) 14
    Osteolysis 1/723 (0.1%) 1 0/734 (0%) 0
    Rhabdomyolysis 0/723 (0%) 0 1/734 (0.1%) 2
    Rotator cuff syndrome 0/723 (0%) 0 2/734 (0.3%) 2
    Spinal column stenosis 1/723 (0.1%) 1 0/734 (0%) 0
    Spondylolisthesis 0/723 (0%) 0 1/734 (0.1%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon 0/723 (0%) 0 1/734 (0.1%) 1
    Basal cell carcinoma 0/723 (0%) 0 1/734 (0.1%) 1
    Benign soft tissue neoplasm 1/723 (0.1%) 1 0/734 (0%) 0
    Bladder cancer 1/723 (0.1%) 1 2/734 (0.3%) 2
    Bladder cancer recurrent 0/723 (0%) 0 2/734 (0.3%) 2
    Bladder transitional cell carcinoma 1/723 (0.1%) 1 0/734 (0%) 0
    Brain neoplasm 1/723 (0.1%) 1 0/734 (0%) 0
    Breast cancer 0/723 (0%) 0 3/734 (0.4%) 3
    Breast cancer metastatic 1/723 (0.1%) 1 0/734 (0%) 0
    Chronic myeloid leukaemia 1/723 (0.1%) 1 0/734 (0%) 0
    Colon cancer 2/723 (0.3%) 2 0/734 (0%) 0
    Colon cancer metastatic 1/723 (0.1%) 1 0/734 (0%) 0
    Essential thrombocythaemia 1/723 (0.1%) 1 0/734 (0%) 0
    Gastric cancer 1/723 (0.1%) 1 2/734 (0.3%) 2
    Granular cell tumour 0/723 (0%) 0 1/734 (0.1%) 1
    Invasive ductal breast carcinoma 1/723 (0.1%) 1 0/734 (0%) 0
    Lung cancer metastatic 1/723 (0.1%) 1 0/734 (0%) 0
    Lung carcinoma cell type unspecified stage iv 1/723 (0.1%) 1 0/734 (0%) 0
    Lung neoplasm malignant 0/723 (0%) 0 1/734 (0.1%) 1
    Lymphoma 0/723 (0%) 0 1/734 (0.1%) 1
    Malignant melanoma 1/723 (0.1%) 1 0/734 (0%) 0
    Malignant neoplasm of unknown primary site 0/723 (0%) 0 1/734 (0.1%) 1
    Malignant neoplasm progression 0/723 (0%) 0 1/734 (0.1%) 1
    Metastases to liver 0/723 (0%) 0 1/734 (0.1%) 1
    Metastatic malignant melanoma 0/723 (0%) 0 1/734 (0.1%) 1
    Neoplasm 1/723 (0.1%) 1 0/734 (0%) 0
    Non-small cell lung cancer 3/723 (0.4%) 3 0/734 (0%) 0
    Oesophageal adenocarcinoma 0/723 (0%) 0 1/734 (0.1%) 1
    Pancreatic carcinoma 1/723 (0.1%) 1 0/734 (0%) 0
    Pancreatic carcinoma metastatic 0/723 (0%) 0 1/734 (0.1%) 1
    Pancreatic neoplasm 1/723 (0.1%) 1 0/734 (0%) 0
    Papillary thyroid cancer 0/723 (0%) 0 1/734 (0.1%) 1
    Plasma cell myeloma 1/723 (0.1%) 1 1/734 (0.1%) 1
    Plasmacytoma 1/723 (0.1%) 3 0/734 (0%) 0
    Prostate cancer metastatic 0/317 (0%) 0 1/319 (0.3%) 1
    Rectal cancer 0/723 (0%) 0 1/734 (0.1%) 1
    Renal cell carcinoma 0/723 (0%) 0 1/734 (0.1%) 1
    Renal neoplasm 1/723 (0.1%) 1 0/734 (0%) 0
    Salivary gland neoplasm 0/723 (0%) 0 1/734 (0.1%) 1
    Squamous cell carcinoma of skin 1/723 (0.1%) 1 0/734 (0%) 0
    Uterine cancer 1/406 (0.2%) 1 0/415 (0%) 0
    Nervous system disorders
    Altered state of consciousness 2/723 (0.3%) 2 0/734 (0%) 0
    Brain stem haemorrhage 2/723 (0.3%) 2 0/734 (0%) 0
    Brain stem infarction 1/723 (0.1%) 1 0/734 (0%) 0
    Cerebral haematoma 1/723 (0.1%) 1 0/734 (0%) 0
    Cerebral haemorrhage 3/723 (0.4%) 3 1/734 (0.1%) 1
    Cerebral infarction 3/723 (0.4%) 3 4/734 (0.5%) 4
    Cerebral microhaemorrhage 1/723 (0.1%) 1 0/734 (0%) 0
    Cerebrospinal fluid leakage 1/723 (0.1%) 3 0/734 (0%) 0
    Cerebrovascular accident 1/723 (0.1%) 1 3/734 (0.4%) 3
    Circadian rhythm sleep disorder 0/723 (0%) 0 1/734 (0.1%) 1
    Cognitive disorder 0/723 (0%) 0 3/734 (0.4%) 3
    Coma 0/723 (0%) 0 1/734 (0.1%) 1
    Complex partial seizures 2/723 (0.3%) 2 0/734 (0%) 0
    Dementia alzheimer's type 8/723 (1.1%) 8 5/734 (0.7%) 5
    Dementia with lewy bodies 1/723 (0.1%) 1 0/734 (0%) 0
    Depressed level of consciousness 1/723 (0.1%) 1 1/734 (0.1%) 1
    Dizziness 1/723 (0.1%) 1 1/734 (0.1%) 1
    Encephalopathy 3/723 (0.4%) 4 1/734 (0.1%) 1
    Epilepsy 1/723 (0.1%) 1 1/734 (0.1%) 1
    Generalised tonic-clonic seizure 2/723 (0.3%) 2 1/734 (0.1%) 1
    Haemorrhage intracranial 0/723 (0%) 0 1/734 (0.1%) 1
    Haemorrhagic cerebral infarction 1/723 (0.1%) 1 0/734 (0%) 0
    Haemorrhagic stroke 0/723 (0%) 0 1/734 (0.1%) 1
    Headache 3/723 (0.4%) 3 1/734 (0.1%) 1
    Hemiparesis 1/723 (0.1%) 1 0/734 (0%) 0
    Hypoxic-ischaemic encephalopathy 0/723 (0%) 0 1/734 (0.1%) 1
    Intracranial aneurysm 1/723 (0.1%) 1 0/734 (0%) 0
    Intraventricular haemorrhage 0/723 (0%) 0 1/734 (0.1%) 1
    Ischaemic cerebral infarction 1/723 (0.1%) 1 0/734 (0%) 0
    Ischaemic stroke 6/723 (0.8%) 6 0/734 (0%) 0
    Lethargy 0/723 (0%) 0 2/734 (0.3%) 2
    Loss of consciousness 2/723 (0.3%) 2 1/734 (0.1%) 1
    Metabolic encephalopathy 1/723 (0.1%) 1 1/734 (0.1%) 1
    Myoclonus 1/723 (0.1%) 1 1/734 (0.1%) 1
    Normal pressure hydrocephalus 2/723 (0.3%) 2 1/734 (0.1%) 1
    Presyncope 2/723 (0.3%) 2 2/734 (0.3%) 2
    Seizure 3/723 (0.4%) 3 11/734 (1.5%) 13
    Somnolence 0/723 (0%) 0 2/734 (0.3%) 2
    Subarachnoid haemorrhage 0/723 (0%) 0 1/734 (0.1%) 1
    Syncope 10/723 (1.4%) 10 15/734 (2%) 16
    Transient ischaemic attack 3/723 (0.4%) 3 2/734 (0.3%) 2
    Tremor 1/723 (0.1%) 1 0/734 (0%) 0
    Vasogenic cerebral oedema 1/723 (0.1%) 1 0/734 (0%) 0
    Psychiatric disorders
    Abnormal behaviour 0/723 (0%) 0 1/734 (0.1%) 1
    Affective disorder 0/723 (0%) 0 1/734 (0.1%) 1
    Aggression 2/723 (0.3%) 2 2/734 (0.3%) 7
    Agitation 11/723 (1.5%) 11 7/734 (1%) 7
    Alcohol abuse 0/723 (0%) 0 1/734 (0.1%) 1
    Behavioural and psychiatric symptoms of dementia 7/723 (1%) 10 3/734 (0.4%) 3
    Bipolar disorder 0/723 (0%) 0 1/734 (0.1%) 1
    Completed suicide 1/723 (0.1%) 1 0/734 (0%) 0
    Confusional state 1/723 (0.1%) 1 6/734 (0.8%) 6
    Delirium 5/723 (0.7%) 5 5/734 (0.7%) 5
    Delirium febrile 1/723 (0.1%) 1 0/734 (0%) 0
    Delusion 3/723 (0.4%) 3 2/734 (0.3%) 2
    Delusional perception 0/723 (0%) 0 1/734 (0.1%) 3
    Disorientation 1/723 (0.1%) 1 0/734 (0%) 0
    Insomnia 0/723 (0%) 0 1/734 (0.1%) 1
    Irritability 3/723 (0.4%) 4 0/734 (0%) 0
    Major depression 0/723 (0%) 0 1/734 (0.1%) 1
    Mental status changes 5/723 (0.7%) 5 2/734 (0.3%) 2
    Restlessness 2/723 (0.3%) 2 0/734 (0%) 0
    Suicidal behaviour 1/723 (0.1%) 1 0/734 (0%) 0
    Suicidal ideation 1/723 (0.1%) 1 0/734 (0%) 0
    Suicide attempt 0/723 (0%) 0 1/734 (0.1%) 1
    Renal and urinary disorders
    Acute kidney injury 6/723 (0.8%) 6 2/734 (0.3%) 2
    Acute prerenal failure 0/723 (0%) 0 1/734 (0.1%) 1
    Bladder tamponade 0/723 (0%) 0 1/734 (0.1%) 1
    Calculus bladder 0/723 (0%) 0 1/734 (0.1%) 1
    Haematuria 0/723 (0%) 0 1/734 (0.1%) 1
    Hydronephrosis 0/723 (0%) 0 1/734 (0.1%) 1
    Nephrolithiasis 2/723 (0.3%) 2 1/734 (0.1%) 1
    Renal failure 0/723 (0%) 0 1/734 (0.1%) 1
    Urinary bladder haemorrhage 1/723 (0.1%) 1 0/734 (0%) 0
    Urinary retention 3/723 (0.4%) 3 3/734 (0.4%) 3
    Reproductive system and breast disorders
    Acquired hydrocele 0/317 (0%) 0 1/319 (0.3%) 1
    Benign prostatic hyperplasia 2/317 (0.6%) 2 1/319 (0.3%) 1
    Cystocele 1/406 (0.2%) 1 0/415 (0%) 0
    Prostatomegaly 0/317 (0%) 0 1/319 (0.3%) 1
    Uterine prolapse 1/406 (0.2%) 1 0/415 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema 0/723 (0%) 0 1/734 (0.1%) 1
    Acute respiratory failure 1/723 (0.1%) 1 1/734 (0.1%) 1
    Aspiration 1/723 (0.1%) 1 1/734 (0.1%) 1
    Bronchospasm 0/723 (0%) 0 1/734 (0.1%) 2
    Chronic obstructive pulmonary disease 2/723 (0.3%) 2 1/734 (0.1%) 1
    Dyspnoea 3/723 (0.4%) 3 1/734 (0.1%) 1
    Hypoxia 1/723 (0.1%) 1 0/734 (0%) 0
    Interstitial lung disease 1/723 (0.1%) 1 0/734 (0%) 0
    Lung disorder 1/723 (0.1%) 1 0/734 (0%) 0
    Nasal polyps 1/723 (0.1%) 1 0/734 (0%) 0
    Organising pneumonia 0/723 (0%) 0 1/734 (0.1%) 1
    Pharyngeal oedema 1/723 (0.1%) 1 0/734 (0%) 0
    Pleural effusion 4/723 (0.6%) 4 0/734 (0%) 0
    Pneumonia aspiration 5/723 (0.7%) 5 5/734 (0.7%) 6
    Pneumothorax 0/723 (0%) 0 1/734 (0.1%) 1
    Pneumothorax spontaneous 0/723 (0%) 0 1/734 (0.1%) 1
    Pulmonary embolism 1/723 (0.1%) 1 6/734 (0.8%) 6
    Respiratory distress 1/723 (0.1%) 1 0/734 (0%) 0
    Respiratory failure 2/723 (0.3%) 2 3/734 (0.4%) 3
    Skin and subcutaneous tissue disorders
    Dermatitis contact 1/723 (0.1%) 1 0/734 (0%) 0
    Diabetic foot 0/723 (0%) 0 1/734 (0.1%) 1
    Drug eruption 1/723 (0.1%) 1 0/734 (0%) 0
    Hypersensitivity vasculitis 1/723 (0.1%) 1 0/734 (0%) 0
    Sebaceous gland disorder 0/723 (0%) 0 1/734 (0.1%) 1
    Urticaria 0/723 (0%) 0 1/734 (0.1%) 1
    Social circumstances
    Activities of daily living impaired 1/723 (0.1%) 1 0/734 (0%) 0
    Surgical and medical procedures
    Cataract operation 1/723 (0.1%) 2 0/734 (0%) 0
    Vascular disorders
    Aortic aneurysm 0/723 (0%) 0 1/734 (0.1%) 1
    Aortic stenosis 1/723 (0.1%) 1 0/734 (0%) 0
    Arterial thrombosis 0/723 (0%) 0 1/734 (0.1%) 1
    Arteriosclerosis 1/723 (0.1%) 1 0/734 (0%) 0
    Deep vein thrombosis 1/723 (0.1%) 1 6/734 (0.8%) 7
    Haematoma 1/723 (0.1%) 1 0/734 (0%) 0
    Hypertensive crisis 1/723 (0.1%) 2 1/734 (0.1%) 1
    Hypotension 1/723 (0.1%) 1 1/734 (0.1%) 1
    Peripheral artery thrombosis 1/723 (0.1%) 1 0/734 (0%) 0
    Peripheral ischaemia 1/723 (0.1%) 1 0/734 (0%) 0
    Shock 0/723 (0%) 0 1/734 (0.1%) 1
    Thromboangiitis obliterans 0/723 (0%) 0 1/734 (0.1%) 1
    Thrombophlebitis 1/723 (0.1%) 1 0/734 (0%) 0
    Venous thrombosis 1/723 (0.1%) 1 0/734 (0%) 0
    Other (Not Including Serious) Adverse Events
    Placebo Solanezumab
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 485/723 (67.1%) 514/734 (70%)
    Gastrointestinal disorders
    Constipation 51/723 (7.1%) 56 64/734 (8.7%) 71
    Diarrhoea 58/723 (8%) 72 76/734 (10.4%) 105
    Vomiting 41/723 (5.7%) 51 51/734 (6.9%) 70
    General disorders
    Oedema peripheral 31/723 (4.3%) 33 37/734 (5%) 38
    Infections and infestations
    Bronchitis 32/723 (4.4%) 47 43/734 (5.9%) 56
    Nasopharyngitis 78/723 (10.8%) 129 88/734 (12%) 145
    Upper respiratory tract infection 59/723 (8.2%) 73 47/734 (6.4%) 61
    Urinary tract infection 98/723 (13.6%) 153 84/734 (11.4%) 161
    Injury, poisoning and procedural complications
    Contusion 45/723 (6.2%) 62 58/734 (7.9%) 84
    Fall 145/723 (20.1%) 222 136/734 (18.5%) 245
    Investigations
    Weight decreased 48/723 (6.6%) 51 38/734 (5.2%) 40
    Metabolism and nutrition disorders
    Decreased appetite 35/723 (4.8%) 39 37/734 (5%) 44
    Musculoskeletal and connective tissue disorders
    Arthralgia 42/723 (5.8%) 51 33/734 (4.5%) 40
    Back pain 49/723 (6.8%) 54 67/734 (9.1%) 75
    Nervous system disorders
    Cerebral microhaemorrhage 42/723 (5.8%) 47 56/734 (7.6%) 61
    Dizziness 39/723 (5.4%) 43 43/734 (5.9%) 53
    Headache 49/723 (6.8%) 65 46/734 (6.3%) 64
    Psychiatric disorders
    Agitation 75/723 (10.4%) 83 64/734 (8.7%) 72
    Anxiety 56/723 (7.7%) 78 86/734 (11.7%) 114
    Insomnia 67/723 (9.3%) 70 74/734 (10.1%) 80
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 17/317 (5.4%) 17 9/319 (2.8%) 10
    Respiratory, thoracic and mediastinal disorders
    Cough 50/723 (6.9%) 61 66/734 (9%) 74
    Vascular disorders
    Hypertension 42/723 (5.8%) 43 36/734 (4.9%) 38

    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. 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:
    NCT01127633
    Other Study ID Numbers:
    • 11935
    • H8A-MC-LZAO
    First Posted:
    May 21, 2010
    Last Update Posted:
    Oct 8, 2019
    Last Verified:
    Sep 1, 2019