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Clinical Trial Results:
Assessment of Safety, Tolerability, and Efficacy of Donanemab in Early Symptomatic Alzheimer’s Disease

Summary
EudraCT number	2020-000077-25
Trial protocol	PL NL CZ
Global end of trial date

Results information
Results version number	v1(current)
This version publication date	27 Apr 2024
First version publication date	27 Apr 2024
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

I5T-MC-AACI

ISRCTN number

US NCT number

NCT04437511

WHO universal trial number (UTN)

Other trial identifiers

Trial Number: 17737

Sponsor organisation name

Eli Lilly and Company

Sponsor organisation address

Lilly Corporate Center, Indianapolis, IN, United States, 46285

Public contact

Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,

Scientific contact

Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Interim

Date of interim/final analysis

14 Apr 2023

Is this the analysis of the primary completion data?

Yes

Primary completion date

14 Apr 2023

Global end of trial reached?

Main objective of the trial

The reason for this study is to see how safe and effective the study drug donanemab is in participants with early Alzheimer’s disease. Additional participants will be enrolled to an addendum safety cohort. The participants will be administered open-label donanemab.

Protection of trial subjects

This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.

Background therapy

Evidence for comparator

Actual start date of recruitment

19 Jun 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 17

Country: Number of subjects enrolled

Canada: 137

Country: Number of subjects enrolled

Czechia: 22

Country: Number of subjects enrolled

Japan: 88

Country: Number of subjects enrolled

Netherlands: 22

Country: Number of subjects enrolled

Poland: 159

Country: Number of subjects enrolled

United Kingdom: 39

Country: Number of subjects enrolled

United States: 1252

Worldwide total number of subjects

1736

EEA total number of subjects

203

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

176

From 65 to 84 years

1531

85 years and over

Subject disposition

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Recruitment details

Screening details

Not Applicable

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Subject

Are arms mutually exclusive

Yes

Donanemab

Arm description

Participants received 700 milligram (mg) Donanemab every 4 weeks (Q4W) x 3 doses, then 1400 mg Q4W given intravenously (IV) for up to 72 weeks

Arm type

Experimental

Investigational medicinal product name

Donanemab

Investigational medicinal product code

Other name

LY3002813

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Participants received 700 mg Donanemab Q4W x 3 doses, then 1400 mg Q4W given IV for up to 72 weeks.

Placebo

Arm description

Participants received placebo given IV.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Participants received placebo given IV.

Number of subjects in period 1	Donanemab	Placebo
Started	860	876
Received at Least One Dose of Drug	853	874
Completed	622	698
Not completed	238	178
Adverse event, serious fatal	15	10
Consent withdrawn by subject	111	94
Physician decision	19	10
Adverse event, non-fatal	50	21
Progressive Disease	4	7
Withdrawal due to Caregiver Circumstances	21	20
Lost to follow-up	11	11
Continuing Study	7	5

Baseline characteristics

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Reporting group title

Donanemab

Reporting group description

Participants received 700 milligram (mg) Donanemab every 4 weeks (Q4W) x 3 doses, then 1400 mg Q4W given intravenously (IV) for up to 72 weeks

Reporting group title

Placebo

Reporting group description

Participants received placebo given IV.

Reporting group values	Donanemab	Placebo	Total
Number of subjects	860	876	1736
Age categorical
Units: Subjects
Age continuous
All randomized participants.
Units: years
arithmetic mean (standard deviation)	72.98 ( 6.16 )	73.04 ( 6.20 )	-
Gender categorical
All randomized participants.
Units: Subjects
Female	493	503	996
Male	367	373	740
Ethnicity (NIH/OMB)
All randomized participants.
Units: Subjects
Hispanic or Latino	35	36	71
Not Hispanic or Latino	583	594	1177
Unknown or Not Reported	242	246	488
Race (NIH/OMB)
All randomized participants.
Units: Subjects
American Indian or Alaska Native	2	0	2
Asian	57	47	104
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	19	21	40
White	781	807	1588
More than one race	0	1	1
Unknown or Not Reported	1	0	1
Region of Enrollment
All randomized participants.
Units: Subjects
Australia	13	4	17
Canada	64	73	137
Czechia	12	10	22
Japan	45	43	88
Netherlands	13	9	22
Poland	77	82	159
United Kingdom	16	23	39
United States	620	632	1252
Screening Tau Category
All randomized participants who have only evaluable Screening Tau category data. Intermediate tau (Low-medium): All participants with baseline composite tau PET standardized uptake value ratio (SUVr) <= 1.46 and a topographic deposition pattern consistent with advanced AD (AD++) or 1.10 <= SUVr <= 1.46 and a topographic deposition pattern consistent with moderate AD (AD+). High tau: All participants with SUVr >1.46 and a topographic deposition pattern consistent with either moderate (AD+) or advanced AD (AD++).
Units: Subjects
Intermediate (Low-medium)	588	594	1182
High	271	281	552
Missing	1	1	2
Integrated Alzheimer's Disease Rating Scale (iADRS)
Integrated Alzheimer's Disease Rating Scale is used to assess whether donanemab slows down the clinical decline associated with AD compared with placebo. iADRS is an integrated assessment of cognition and daily function comprised of items from the Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog13) and the Alzheimer's disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). The scale ranges from 0 to 144, where lower scores indicate worse performance and higher score indicates better performance.
Units: Score on a scale
arithmetic mean (standard deviation)	104.10 ( 14.30 )	103.60 ( 14.02 )	-

End points

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Reporting group title

Donanemab

Reporting group description

Participants received 700 milligram (mg) Donanemab every 4 weeks (Q4W) x 3 doses, then 1400 mg Q4W given intravenously (IV) for up to 72 weeks

Reporting group title

Placebo

Reporting group description

Participants received placebo given IV.

Primary: Change from Baseline on the integrated Alzheimer’s Disease Rating Scale (iADRS) (Overall population)

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End point title

Change from Baseline on the integrated Alzheimer’s Disease Rating Scale (iADRS) (Overall population)

End point description

Integrated Alzheimer's Disease Rating Scale is used to assess whether donanemab slows down the clinical decline associated with AD compared with placebo. iADRS is an integrated assessment of cognition and daily function comprised of items from the Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog13) and the Alzheimer's disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). The scale ranges from 0 to 144, where lower scores indicate worse performance and higher score indicates better performance. Least Squares (LS) Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, baseline tau level, and baseline acetylcholinesterase inhibitor (AchI)/Memantine use. Analysis population description (APD) included all randomized participants with a baseline and at least one postbaseline iADRS data point.

End point type

Primary

End point timeframe

Baseline, Week 76

End point values	Donanemab	Placebo
Number of subjects analysed	775	824
Units: score on a scale
least squares mean (standard error)	-10.19 ( 0.53 )	-13.11 ( 0.50 )

Change from Baseline on iADRS

Statistical analysis description

Overall population

Comparison groups

Donanemab v Placebo

Number of subjects included in analysis

1599

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean change difference (Final Values)

Point estimate

2.92

Confidence interval

level

95%

sides

2-sided

lower limit

1.508

upper limit

4.331

Variability estimate

Standard error of the mean

Dispersion value

0.72

Primary: Change from Baseline on the integrated Alzheimer’s Disease Rating Scale (iADRS) (Intermediate (Low-medium) Tau Population)

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End point title

Change from Baseline on the integrated Alzheimer’s Disease Rating Scale (iADRS) (Intermediate (Low-medium) Tau Population)

End point description

Integrated Alzheimer's Disease Rating Scale is used to assess whether donanemab slows down the clinical decline associated with AD compared with placebo. iADRS is an integrated assessment of cognition and daily function comprised of items from the Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog13) and the Alzheimer's disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). The scale ranges from 0 to 144, where lower scores indicate worse performance and higher score indicates better performance. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, and baseline AchI/Memantine use. APD included all randomized participants with baseline Intermediate Tau level and with baseline and at least one postbaseline iADRS data point.

End point type

Primary

End point timeframe

Baseline, Week 76

End point values	Donanemab	Placebo
Number of subjects analysed	533	560
Units: score on a scale
least squares mean (standard error)	-6.02 ( 0.50 )	-9.27 ( 0.49 )

Change from Baseline on iADRS

Statistical analysis description

Intermediate (Low-medium) Tau Population

Comparison groups

Donanemab v Placebo

Number of subjects included in analysis

1093

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean change difference (Final Values)

Point estimate

3.25

Confidence interval

level

95%

sides

2-sided

lower limit

1.883

upper limit

4.618

Variability estimate

Standard error of the mean

Dispersion value

0.7

Secondary: Change from Baseline on the Mini Mental State Examination (MMSE) Score (Overall Population)

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End point title

Change from Baseline on the Mini Mental State Examination (MMSE) Score (Overall Population)

End point description

MMSE is an instrument used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures). Total score ranges from 0 to 30; lower score indicates greater disease severity. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, baseline tau level, and baseline AchI/Memantine use. APD included all randomized participants with a baseline and at least one postbaseline MMSE data point.

End point type

Secondary

End point timeframe

Baseline, Week 76

End point values	Donanemab	Placebo
Number of subjects analysed	796	841
Units: score on a scale
least squares mean (standard error)	-2.47 ( 0.14 )	-2.94 ( 0.13 )

Change from Baseline on MMSE Score

Statistical analysis description

Overall Population

Comparison groups

Donanemab v Placebo

Number of subjects included in analysis

1637

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012

Method

Mixed models analysis

Parameter type

LS Mean change difference (Final Values)

Point estimate

0.47

Confidence interval

level

95%

sides

2-sided

lower limit

0.104

upper limit

0.841

Variability estimate

Standard error of the mean

Dispersion value

0.19

Secondary: Change from Baseline on the Mini Mental State Examination (MMSE) Score (Intermediate (Low-medium) Tau Population)

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End point title

Change from Baseline on the Mini Mental State Examination (MMSE) Score (Intermediate (Low-medium) Tau Population)

End point description

MMSE is an instrument used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures). Total score ranges from 0 to 30; lower score indicates greater disease severity. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, and baseline AchI/Memantine use. APD included all randomized participants with baseline Intermediate Tau level and with baseline and at least one postbaseline MMSE data point.

End point type

Secondary

End point timeframe

Baseline, Week 76

End point values	Donanemab	Placebo
Number of subjects analysed	549	573
Units: score on a scale
least squares mean (standard error)	-1.61 ( 0.14 )	-2.09 ( 0.14 )

Change from Baseline on MMSE Score

Statistical analysis description

Intermediate (Low-medium) Tau Population

Comparison groups

Donanemab v Placebo

Number of subjects included in analysis

1122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.016

Method

Mixed models analysis

Parameter type

LS Mean change difference (Final Values)

Point estimate

0.48

Confidence interval

level

95%

sides

2-sided

lower limit

0.089

upper limit

0.868

Variability estimate

Standard error of the mean

Dispersion value

0.2

Secondary: Change from Baseline on the Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog13) (Overall Population)

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End point title

Change from Baseline on the Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog13) (Overall Population)

End point 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-cog consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS-Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, baseline tau level, and baseline AchI/Memantine use. APD included all randomized participants with a baseline and at least one postbaseline ADAS-Cog13 data point.

End point type

Secondary

End point timeframe

Baseline, Week 76

End point values	Donanemab	Placebo
Number of subjects analysed	797	841
Units: score on a scale
least squares mean (standard error)	5.46 ( 0.28 )	6.79 ( 0.27 )

Change from Baseline on ADAS-Cog13

Statistical analysis description

Overall Population

Comparison groups

Donanemab v Placebo

Number of subjects included in analysis

1638

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0006

Method

Mixed models analysis

Parameter type

LS Mean change difference (Final Values)

Point estimate

-1.33

Confidence interval

level

95%

sides

2-sided

lower limit

-2.086

upper limit

-0.565

Variability estimate

Standard error of the mean

Dispersion value

0.39

Secondary: Change from Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) (Overall Population)

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End point title

Change from Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) (Overall Population)

End point 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 adjusted for treatment, visit, treatment-by-visit interaction, and covariates for baseline score, baseline score-by-visit interaction, age at baseline, baseline tau category, pooled investigator, and baseline AchI/Memantine use. APD included all randomized participants with a baseline and at least one postbaseline CDR-SB data point.

End point type

Secondary

End point timeframe

Baseline, Week 76

End point values	Donanemab	Placebo
Number of subjects analysed	794	838
Units: score on a scale
least squares mean (standard error)	1.72 ( 0.096 )	2.42 ( 0.092 )

Change from Baseline on CDR-SB

Statistical analysis description

Overall Population

Comparison groups

Donanemab v Placebo

Number of subjects included in analysis

1632

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean change difference (Final Values)

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-0.95

upper limit

-0.45

Variability estimate

Standard error of the mean

Dispersion value

0.127

Secondary: Change from Baseline on the Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog13) (Intermediate (Low-medium) Tau Population)

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End point title

Change from Baseline on the Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog13) (Intermediate (Low-medium) Tau Population)

End point description

The ADAS-Cog13 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-Cog13 consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS-Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, and baseline AchI/Memantine use. APD included all randomized participants with baseline Intermediate Tau level and with baseline and at least one postbaseline ADAS-Cog13 data point.

End point type

Secondary

End point timeframe

Baseline, Week 76

End point values	Donanemab	Placebo
Number of subjects analysed	550	570
Units: score on a scale
least squares mean (standard error)	3.17 ( 0.27 )	4.69 ( 0.26 )

Change from Baseline on ADAS-Cog13

Statistical analysis description

Intermediate (Low-medium) Tau Population

Comparison groups

Donanemab v Placebo

Number of subjects included in analysis

1120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean change difference (Final Values)

Point estimate

-1.52

Confidence interval

level

95%

sides

2-sided

lower limit

-2.25

upper limit

-0.794

Variability estimate

Standard error of the mean

Dispersion value

0.37

Secondary: Change from Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) (Intermediate (Low-medium) Tau Population)

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End point title

Change from Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) (Intermediate (Low-medium) Tau Population)

End point 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 adjusted for treatment, visit, treatment-by-visit interaction, and covariates for baseline score, baseline score-by-visit interaction, age at baseline, pooled investigator, and baseline AchI/Memantine use. APD included all randomized participants with baseline Intermediate Tau level and with baseline and at least one postbaseline CDR-SB data point.

End point type

Secondary

End point timeframe

Baseline, Week 76

End point values	Donanemab	Placebo
Number of subjects analysed	546	569
Units: score on a scale
least squares mean (standard error)	1.20 ( 0.105 )	1.88 ( 0.102 )

Change from Baseline on CDR-SB

Statistical analysis description

Intermediate (Low-medium) Tau Population

Comparison groups

Donanemab v Placebo

Number of subjects included in analysis

1115

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean change difference (Final Values)

Point estimate

-0.67

Confidence interval

level

95%

sides

2-sided

lower limit

-0.95

upper limit

-0.4

Variability estimate

Standard error of the mean

Dispersion value

0.141

Secondary: Change from Baseline on the Alzheimer’s Disease Cooperative Study – instrumental Activities of Daily Living (ADCS-iADL) Score (Overall Population)

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End point title

Change from Baseline on the Alzheimer’s Disease Cooperative Study – instrumental Activities of Daily Living (ADCS-iADL) Score (Overall Population)

End point 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 (instrumental activity items 6a, 7-23) of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, baseline tau level, and baseline AchI/Memantine use. APD included all randomized participants with a baseline and at least one postbaseline ADCS-iADL data point.

End point type

Secondary

End point timeframe

Baseline, Week 76

End point values	Donanemab	Placebo
Number of subjects analysed	780	826
Units: score on a scale
least squares mean (standard error)	-4.42 ( 0.32 )	-6.13 ( 0.30 )

Change from Baseline on ADCS-iADL Score

Statistical analysis description

Overall Population

Comparison groups

Donanemab v Placebo

Number of subjects included in analysis

1606

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0001

Method

Mixed models analysis

Parameter type

LS Mean change difference (Final Values)

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

2.566

Variability estimate

Standard error of the mean

Dispersion value

0.44

Secondary: Change from Baseline in Brain Amyloid Plaque Deposition as Measured by Amyloid Positron Emission Tomography (PET) Scan

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End point title

Change from Baseline in Brain Amyloid Plaque Deposition as Measured by Amyloid Positron Emission Tomography (PET) Scan

End point description

Florbetapir or florbetaben PET imaging was used as a quantitative amyloid biomarker. Amyloid PET scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in amyloid plaques. Quantitative amyloid burden was first formalized as the average Standardized Uptake Value Ratio (SUVR) in six predetermined cortical brain regions relative to the cerebellum as a reference region. Larger SUVR reflects the larger cortical amyloid burden relative to cerebellum. SUVR values were further calibrated to a centiloid (CL) scale. The Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scan. LS Mean value was adjusted for treatment, visit, treatment-by-visit interaction, and covariates for baseline score, baseline score-by-visit interaction, baseline tau category, and age at baseline.

End point type

Secondary

End point timeframe

Baseline, Week 76 APD included all randomized participants with a baseline and at least one postbaseline amyloid PET scan data point.

End point values	Donanemab	Placebo
Number of subjects analysed	765	812
Units: centiloids
least squares mean (standard error)	-87.03 ( 0.950 )	-0.67 ( 0.909 )

Change from Baseline in Brain Amyloid Plaque

Comparison groups

Donanemab v Placebo

Number of subjects included in analysis

1577

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

LS Mean change difference (Final Values)

Point estimate

-86.37

Confidence interval

level

95%

sides

2-sided

lower limit

-88.87

upper limit

-83.87

Variability estimate

Standard error of the mean

Dispersion value

1.275

Secondary: Change from Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan

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End point title

Change from Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan

End point description

Flortaucipir PET imaging was used as a quantitative tau biomarker. Tau PET scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in aggregated tau neurofibrillary tangles (NFTs). Quantitative tau burden was formalized using Standardized Uptake Value Ratio (SUVR) in frontal lobe relative to the cerebellum gray as a reference region. Larger SUVR reflects larger tau burden in the frontal lobe relative to cerebellum gray. LS Mean value was adjusted for baseline score, screening tau category, age and treatment (Type III sum of squares). APD included all randomized participants with a baseline and post-baseline tau PET scan.

End point type

Secondary

End point timeframe

Baseline, Week 76

End point values	Donanemab	Placebo
Number of subjects analysed	578	654
Units: standardized uptake value ratio (SUVR)
least squares mean (standard error)	0.0401 ( 0.00398 )	0.0442 ( 0.00374 )

Change from Baseline in Brain Tau Deposition

Comparison groups

Donanemab v Placebo

Number of subjects included in analysis

1232

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4522

Method

ANCOVA

Parameter type

LS Mean change difference (Final Values)

Point estimate

-0.0041

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0148

upper limit

0.0066

Secondary: Change from Baseline in Brain Volume as Measured by volumetric Magnetic Resonance Imaging (vMRI)

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End point title

Change from Baseline in Brain Volume as Measured by volumetric Magnetic Resonance Imaging (vMRI)

End point description

MRI scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in brain volume. Volumetric MRI parameters were measured in bilateral hippocampus, bilateral whole brain, and bilateral ventricles. LS Mean value was adjusted for treatment, visit, treatment-by-visit interaction, and covariates for baseline score, baseline tau category, and age at baseline. APD included all randomized participants with a baseline and at least one postbaseline vMRI data point

End point type

Secondary

End point timeframe

Baseline, Week 76

End point values	Donanemab	Placebo
Number of subjects analysed	786	831
Units: cubic centimeter (cm^3)
least squares mean (standard error)
Bilateral Hippocampus	-0.20 ( 0.005 )	-0.22 ( 0.005 )
Bilateral Whole Brain	-27.46 ( 0.409 )	-20.79 ( 0.392 )
Bilateral Ventricles	10.07 ( 0.185 )	7.05 ( 0.178 )

Change from Baseline in Brain Volume by vMRI

Statistical analysis description

Bilateral Hippocampus

Comparison groups

Donanemab v Placebo

Number of subjects included in analysis

1617

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Mixed models analysis

Parameter type

LS Mean change difference (Final Values)

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.01

upper limit

0.04

Variability estimate

Standard error of the mean

Dispersion value

0.007

Change from Baseline in Brain Volume by vMRI

Statistical analysis description

Bilateral Whole Brain

Comparison groups

Donanemab v Placebo

Number of subjects included in analysis

1617

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean change difference (Final Values)

Point estimate

-6.66

Confidence interval

level

95%

sides

2-sided

lower limit

-7.76

upper limit

-5.56

Variability estimate

Standard error of the mean

Dispersion value

0.561

Change from Baseline in Brain Volume by vMRI

Statistical analysis description

Bilateral Ventricles

Comparison groups

Donanemab v Placebo

Number of subjects included in analysis

1617

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean change difference (Final Values)

Point estimate

3.02

Confidence interval

level

95%

sides

2-sided

lower limit

2.52

upper limit

3.52

Variability estimate

Standard error of the mean

Dispersion value

0.256

Secondary: Pharmacokinetics (PK): Average Serum Concentration at Steady State of Donanemab

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End point title

Pharmacokinetics (PK): Average Serum Concentration at Steady State of Donanemab ^[1]

End point description

The average serum concentration at steady state, calculated as Cav = AUCtau/tau, where tau is the dosing interval (4 weeks). APD included all randomized participants who received at least one dose of study drug and had evaluable PK data.

End point type

Secondary

End point timeframe

Predose: Week 4, 8, 12, 16, 24, 36, 52, 64; Postdose: Week 0, 12, 24, 52 and random at week 76

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: PK endpoint is evaluated only for Donanemab.

End point values	Donanemab
Number of subjects analysed	853
Units: micrograms per milliliter (μg/mL)
geometric mean (geometric coefficient of variation)	63 ( 32 )

No statistical analyses for this end point

Secondary: Number or Participants with Anti-Donanemab Antibodies

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End point title

Number or Participants with Anti-Donanemab Antibodies

End point description

Number of participants with treatment-emergent positive Anti-Donanemab antibodies was summarized by treatment group. APD included all randomized participants who received at least one dose of study drug and had evaluable anti-drug antibody measurement.

End point type

Secondary

End point timeframe

Baseline through Week 76

End point values	Donanemab	Placebo
Number of subjects analysed	793	821
Units: participants	693	48

No statistical analyses for this end point

Secondary: Change From Baseline on the Alzheimer’s Disease Cooperative Study – Instrumental Activities of Daily Living (ADCS-iADL) Score (Intermediate (Low-medium) Tau Population)

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End point title

Change From Baseline on the Alzheimer’s Disease Cooperative Study – Instrumental Activities of Daily Living (ADCS-iADL) Score (Intermediate (Low-medium) Tau Population)

End point 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 (instrumental activity items 6a, 7-23) of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, and baseline AchI/Memantine use. APD included all randomized participants with a baseline Intermediate Tau level and with baseline and at least one postbaseline ADCS-iADL data point.

End point type

Secondary

End point timeframe

Baseline, Week 76

End point values	Donanemab	Placebo
Number of subjects analysed	535	562
Units: score on a scale
least squares mean (standard error)	-2.76 ( 0.34 )	-4.59 ( 0.32 )

Change from Baseline on ADAS-iADL Score

Statistical analysis description

Intermediate (Low-medium) Tau Population

Comparison groups

Donanemab v Placebo

Number of subjects included in analysis

1097

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed models analysis

Parameter type

LS Mean change difference (Final Values)

Point estimate

1.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.913

upper limit

2.748

Variability estimate

Standard error of the mean

Dispersion value

0.47

Adverse events

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Timeframe for reporting adverse events

Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.

Adverse event reporting additional description

Safety population included all randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.1

Reporting group title

Donanemab

Reporting group description

Participants received 700 mg Donanemab Q4W x 3 doses, then 1400 mg Q4W given IV for up to 72 weeks.

Reporting group title

Placebo

Reporting group description

Participants received placebo given IV.

Serious adverse events	Donanemab	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	148 / 853 (17.35%)	138 / 874 (15.79%)
number of deaths (all causes)	16	10
number of deaths resulting from adverse events		0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
adenocarcinoma pancreas
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
bladder cancer
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
bladder papilloma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
breast cancer stage i
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
cervix carcinoma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[1]	0 / 488 (0.00%)	1 / 501 (0.20%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
choroid melanoma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
diffuse large b-cell lymphoma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
endometrial adenocarcinoma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[2]	1 / 488 (0.20%)	0 / 501 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
invasive ductal breast carcinoma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
invasive lobular breast carcinoma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
lung neoplasm malignant
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
lung adenocarcinoma stage iv
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
lymphoproliferative disorder
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
metaplastic breast carcinoma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[3]	0 / 488 (0.00%)	1 / 501 (0.20%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
mucinous breast carcinoma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
non-hodgkin's lymphoma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
pancreatic carcinoma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
plasma cell myeloma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 853 (0.23%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
prostate cancer
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[4]	2 / 365 (0.55%)	1 / 373 (0.27%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
rectal cancer
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	2 / 874 (0.23%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
schwannoma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
aortic stenosis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
arteriosclerosis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
circulatory collapse
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
essential hypertension
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
hypertensive emergency
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
hypotension
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
labile hypertension
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
orthostatic hypotension
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	2 / 874 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
subclavian steal syndrome
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
asthenia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
chest pain
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
chest discomfort
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
death
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	3 / 853 (0.35%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	1 / 3	0 / 1
deaths causally related to treatment / all	1 / 3	0 / 1
medical device site pain
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
non-cardiac chest pain
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 853 (0.23%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Immune system disorders
infusion related hypersensitivity reaction
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
benign prostatic hyperplasia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[5]	2 / 365 (0.55%)	0 / 373 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
priapism
alternative dictionary used: MedDRA 25.1
subjects affected / exposed ^[6]	1 / 365 (0.27%)	0 / 373 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
acute respiratory failure
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
dyspnoea
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
haemoptysis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
hypoxia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
pneumonitis aspiration
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
pneumothorax
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	3 / 853 (0.35%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
pulmonary embolism
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	4 / 853 (0.47%)	2 / 874 (0.23%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 2	0 / 0
respiratory distress
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
respiratory arrest
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
respiratory failure
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
sleep apnoea syndrome
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
agitation
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	4 / 853 (0.47%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
alcohol abuse
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
anxiety
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
behaviour disorder
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
completed suicide
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 853 (0.23%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 2	0 / 1
confusional state
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	2 / 874 (0.23%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
delirium
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	3 / 853 (0.35%)	3 / 874 (0.34%)
occurrences causally related to treatment / all	1 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
hallucination, visual
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
mental status changes
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 853 (0.23%)	3 / 874 (0.34%)
occurrences causally related to treatment / all	0 / 2	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
mental disorder
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
suicide attempt
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
electrocardiogram qt prolonged
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
troponin increased
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
accidental overdose
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
anaesthetic complication
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
carbon monoxide poisoning
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
contusion
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
fall
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	5 / 853 (0.59%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 5	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
femur fracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 853 (0.23%)	2 / 874 (0.23%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
femoral neck fracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	2 / 874 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
forearm fracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
head injury
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
hip fracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
infusion related reaction
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
lower limb fracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
lumbar vertebral fracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
multiple fractures
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
periprosthetic fracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
pelvic fracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
pneumothorax traumatic
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
post procedural haemorrhage
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
radius fracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
respiratory fume inhalation disorder
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
rib fracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
road traffic accident
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
skin laceration
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
spinal compression fracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
spinal fracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
stress fracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
sternal fracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
subdural haematoma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	3 / 853 (0.35%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
thoracic vertebral fracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 853 (0.23%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
wrist fracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
acute myocardial infarction
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	5 / 853 (0.59%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
angina pectoris
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 853 (0.23%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	1 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
atrioventricular block complete
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
atrial fibrillation
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	4 / 874 (0.46%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
bradycardia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	2 / 874 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
cardiac arrest
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
coronary artery disease
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	2 / 874 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
myocardial infarction
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
sinus bradycardia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
sinus node dysfunction
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
ventricular fibrillation
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
amnesia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
amyloid related imaging abnormality-oedema/effusion
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	13 / 853 (1.52%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	13 / 13	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0
amyloid related imaging abnormality-microhaemorrhages and haemosiderin deposits
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	4 / 853 (0.47%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	4 / 4	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0
balance disorder
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
cerebellar infarction
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
cerebrovascular accident
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
cervical radiculopathy
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
dementia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
dementia alzheimer's type
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 853 (0.23%)	2 / 874 (0.23%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 1
dizziness
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
dysarthria
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
embolic stroke
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
haemorrhagic stroke
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
ischaemic cerebral infarction
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
ischaemic stroke
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
loss of consciousness
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
neurological symptom
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
presyncope
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	2 / 874 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
seizure
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	3 / 853 (0.35%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	1 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
subarachnoid haemorrhage
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 853 (0.23%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
syncope
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	9 / 853 (1.06%)	13 / 874 (1.49%)
occurrences causally related to treatment / all	1 / 9	0 / 13
deaths causally related to treatment / all	0 / 0	0 / 0
transient ischaemic attack
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	3 / 874 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Ear and labyrinth disorders
vertigo
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
visual impairment
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
abdominal discomfort
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
abdominal wall haematoma
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
colitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
diarrhoea
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
duodenitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
enterovesical fistula
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
femoral hernia strangulated
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
gastric ulcer perforation
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
gastric antral vascular ectasia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
gastritis erosive
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
gastrooesophageal reflux disease
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
intestinal obstruction
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
inguinal hernia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 853 (0.23%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
intestinal perforation
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
large intestine perforation
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
large intestine polyp
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
lower gastrointestinal haemorrhage
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
oesophagitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
obstruction gastric
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
obstructive pancreatitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
pancreatitis acute
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 853 (0.23%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
pancreatitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
rectal prolapse
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
retroperitoneal haemorrhage
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
small intestinal obstruction
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	3 / 853 (0.35%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
small intestinal perforation
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
upper gastrointestinal haemorrhage
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
bile duct stone
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
cholecystitis acute
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
cholelithiasis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
erythema
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
urticaria
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
acute kidney injury
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	4 / 853 (0.47%)	2 / 874 (0.23%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
chronic kidney disease
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
haematuria
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
nephrolithiasis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	2 / 874 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
urinary bladder haemorrhage
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
urinary retention
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
urinary tract obstruction
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
arthritis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
musculoskeletal chest pain
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
osteoporotic fracture
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
rotator cuff syndrome
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	2 / 874 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
spinal stenosis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
abscess limb
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
appendicitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	2 / 874 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
appendicitis perforated
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
bacterial sepsis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
covid-19
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	9 / 853 (1.06%)	4 / 874 (0.46%)
occurrences causally related to treatment / all	0 / 9	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 0
covid-19 pneumonia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	3 / 874 (0.34%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 1	0 / 0
cellulitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
cystitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
diverticulitis intestinal perforated
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
diverticulitis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
enterococcal bacteraemia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
escherichia sepsis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
influenza
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	2 / 874 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
pelvic abscess
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
pneumonia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	5 / 853 (0.59%)	5 / 874 (0.57%)
occurrences causally related to treatment / all	1 / 6	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 2
pneumonia aspiration
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
pneumonia legionella
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
pyelonephritis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
sepsis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 853 (0.23%)	3 / 874 (0.34%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1
staphylococcal bacteraemia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
staphylococcal infection
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
urinary tract infection
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	3 / 853 (0.35%)	4 / 874 (0.46%)
occurrences causally related to treatment / all	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
urinary tract infection pseudomonal
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
urosepsis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
decreased appetite
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
dehydration
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	3 / 853 (0.35%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
diabetes mellitus inadequate control
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
diabetic ketoacidosis
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
hypokalaemia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	1 / 853 (0.12%)	0 / 874 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
hyponatraemia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	2 / 853 (0.23%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
hypovolaemia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	0 / 853 (0.00%)	1 / 874 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Donanemab	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	567 / 853 (66.47%)	425 / 874 (48.63%)
Injury, poisoning and procedural complications
infusion related reaction
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	73 / 853 (8.56%)	4 / 874 (0.46%)
occurrences all number	166	7
fall
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	111 / 853 (13.01%)	109 / 874 (12.47%)
occurrences all number	149	141
Nervous system disorders
amyloid related imaging abnormality-microhaemorrhages and haemosiderin deposits
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	166 / 853 (19.46%)	65 / 874 (7.44%)
occurrences all number	225	77
amyloid related imaging abnormality-oedema/effusion
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	200 / 853 (23.45%)	17 / 874 (1.95%)
occurrences all number	270	17
dizziness
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	52 / 853 (6.10%)	48 / 874 (5.49%)
occurrences all number	59	60
headache
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	119 / 853 (13.95%)	86 / 874 (9.84%)
occurrences all number	188	105
superficial siderosis of central nervous system
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	58 / 853 (6.80%)	10 / 874 (1.14%)
occurrences all number	84	12
General disorders and administration site conditions
fatigue
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	42 / 853 (4.92%)	45 / 874 (5.15%)
occurrences all number	43	68
Gastrointestinal disorders
diarrhoea
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	43 / 853 (5.04%)	50 / 874 (5.72%)
occurrences all number	51	56
Musculoskeletal and connective tissue disorders
arthralgia
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	49 / 853 (5.74%)	41 / 874 (4.69%)
occurrences all number	55	44
Infections and infestations
covid-19
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	130 / 853 (15.24%)	150 / 874 (17.16%)
occurrences all number	135	157
urinary tract infection
alternative dictionary used: MedDRA 25.1
subjects affected / exposed	42 / 853 (4.92%)	56 / 874 (6.41%)
occurrences all number	52	65

More information

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Were there any global substantial amendments to the protocol? Yes

14 Dec 2020

- Added titration period of 700 mg for first 3 doses; - Added instructions for when a participant does not complete the titration phase; - Added instructions for when a participant develops amyloid-related imaging abnormalities (ARIA).

17 Feb 2021

- Updated study to Phase 3; - Updated screening window and follow up and clarified notes in schedule of activities; - Clarification for scientific rationale for study design, justification for dose, Inclusion criteria, study interventions, efficacy and Clinical Safety laboratory assessments, Pharmacokinetics, Statistical considerations; - Modified language describing interim analyses, data monitoring committee (DMC) members description, -safety profile of flortaucipir.

03 Sep 2021

- Modified Number of Participants; - Added description of blinding for Cohorts 1 and 2; - Added and defined Cohorts 1 and 2; - Added details related to the Cohort 1 statistical analysis plan (SAP) and Study SAP; - Added “Interim analyses of Cohort 1 will be conducted by Lilly. Specified that other interim analyses involving Cohort 2 will be executed through the external data monitoring committee (DMC).

05 Oct 2021

- Clarification on schedule of Activities; - Modified description of primary endpoint. Added rationale and design details for long-term extension period; -Modified Inclusion Criteria; -Added recommendation of data monitoring committee (DMC); - Clarification on text regarding magnetic resonance imaging; - Clarification on time period and frequency for collecting AE and SAE Information; - Added clarifying text regarding Sample size determination; - Added details related to the Primary, secondary and tertiary/exploratory endpoint(s).

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: Assessment of Safety, Tolerability, and Efficacy of Donanemab in Early Symptomatic Alzheimer’s Disease

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from Baseline on the integrated Alzheimer’s Disease Rating Scale (iADRS) (Overall population)

Primary: Change from Baseline on the integrated Alzheimer’s Disease Rating Scale (iADRS) (Overall population)

Primary: Change from Baseline on the integrated Alzheimer’s Disease Rating Scale (iADRS) (Intermediate (Low-medium) Tau Population)

Primary: Change from Baseline on the integrated Alzheimer’s Disease Rating Scale (iADRS) (Intermediate (Low-medium) Tau Population)

Secondary: Change from Baseline on the Mini Mental State Examination (MMSE) Score (Overall Population)

Secondary: Change from Baseline on the Mini Mental State Examination (MMSE) Score (Overall Population)

Secondary: Change from Baseline on the Mini Mental State Examination (MMSE) Score (Intermediate (Low-medium) Tau Population)

Secondary: Change from Baseline on the Mini Mental State Examination (MMSE) Score (Intermediate (Low-medium) Tau Population)

Secondary: Change from Baseline on the Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog13) (Overall Population)

Secondary: Change from Baseline on the Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog13) (Overall Population)

Secondary: Change from Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) (Overall Population)

Secondary: Change from Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) (Overall Population)

Secondary: Change from Baseline on the Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog13) (Intermediate (Low-medium) Tau Population)

Secondary: Change from Baseline on the Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog13) (Intermediate (Low-medium) Tau Population)

Secondary: Change from Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) (Intermediate (Low-medium) Tau Population)

Secondary: Change from Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) (Intermediate (Low-medium) Tau Population)

Secondary: Change from Baseline on the Alzheimer’s Disease Cooperative Study – instrumental Activities of Daily Living (ADCS-iADL) Score (Overall Population)

Secondary: Change from Baseline on the Alzheimer’s Disease Cooperative Study – instrumental Activities of Daily Living (ADCS-iADL) Score (Overall Population)

Secondary: Change from Baseline in Brain Amyloid Plaque Deposition as Measured by Amyloid Positron Emission Tomography (PET) Scan

Secondary: Change from Baseline in Brain Amyloid Plaque Deposition as Measured by Amyloid Positron Emission Tomography (PET) Scan

Secondary: Change from Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan

Secondary: Change from Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan

Secondary: Change from Baseline in Brain Volume as Measured by volumetric Magnetic Resonance Imaging (vMRI)

Secondary: Change from Baseline in Brain Volume as Measured by volumetric Magnetic Resonance Imaging (vMRI)

Secondary: Pharmacokinetics (PK): Average Serum Concentration at Steady State of Donanemab

Secondary: Pharmacokinetics (PK): Average Serum Concentration at Steady State of Donanemab

Secondary: Number or Participants with Anti-Donanemab Antibodies

Secondary: Number or Participants with Anti-Donanemab Antibodies

Secondary: Change From Baseline on the Alzheimer’s Disease Cooperative Study – Instrumental Activities of Daily Living (ADCS-iADL) Score (Intermediate (Low-medium) Tau Population)

Secondary: Change From Baseline on the Alzheimer’s Disease Cooperative Study – Instrumental Activities of Daily Living (ADCS-iADL) Score (Intermediate (Low-medium) Tau Population)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Assessment of Safety, Tolerability, and Efficacy of Donanemab in Early Symptomatic Alzheimer’s Disease