Simufilam 100 mg for Mild-to-Moderate Alzheimer's Disease | NCT04994483

Status Module

Name	Class
Premier Research	OTHER

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 52 weeks	Drug: Placebo
Simufilam 100 mg	Experimental	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 52 weeks	Drug: Simufilam

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Simufilam	Drug	Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 52 weeks at a dose of 100 mg.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in the 12-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12)	The change from baseline to Week 52 in the ADAS-Cog12, a psychometrician-administered battery comprised of several cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Scores range from 0 (best) to 80 (worst).	Baseline (Study Day 1) to Week 52
Change From Baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)	The change from baseline to Week 52 in the ADCS-ADL, a 23-item study partner questionnaire that covers both basic activities of daily living (ADL) and more complex ADL or instrumental ADL. Scores range from 0 to 78, with a lower score indicating greater severity of functional loss.	Baseline (Study Day 1) to Week 52

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in the Integrated Alzheimer's Disease Rating Scale (iADRS)	The change from baseline to Week 52 in the iADRS, where scores range from 0 to 146 with lower scores indicating worse performance.	Baseline (Study Day 1) to Week 52
Change From Baseline in the Neuropsychiatric Inventory (NPI)

Other Outcomes

Measure	Description	Time Frame
Changes From Baseline in Plasma Biomarkers	Change from baseline in the following plasma biomarkers of AD pathology, neurodegeneration, and neuroinflammation: phospho-tau217 (P-tau217), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and total tau.	Baseline (Study Day 1) to Week 52
Changes From Baseline in the Plasma SavaDx Biomarker

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Meets National Institute on Aging and Alzheimer's Association Research Framework criteria for individuals in clinical Stage 4 or 5 of the Alzheimer's continuum.
Evidence for AD pathophysiology, confirmed either prior to or during screening.
MMSE score ≥ 16 and ≤ 27 at screening.
Clinical Dementia Rating - Global Score must be 0.5, 1 or 2.
If receiving background AD medications, the dosing regimen must be stable for at least 12 weeks prior to randomization. Chronic medications for conditions other than AD (such as depression) must be prescribed at a stable dose for at least 4 weeks prior to screening.
The subject has not been a cigarette smoker or chewed tobacco for at least 3 years.
Availability of a study partner.
Individuals who have participated in a clinical study with an investigational drug targeting the underlying AD process may be permitted to participate in this study.
Completed a COVID-19 vaccine primary series ("fully vaccinated") at least 2 weeks prior to randomization or had an unambiguous COVID-19 infection diagnosed more than 3 months before the start of the Screening Period.

Key Exclusion Criteria:

A neurologic condition other than AD that significantly contributes to the subject's dementia.
Any current primary psychiatric diagnosis other than AD if it is likely to confound cognitive assessment or ability to comply with study procedures.
Geriatric Depression Scale (15-item) score > 8. (Note - a subject with a score > 8 may continue in screening if, in the judgment of the Investigator, the elevated score is not attributed to a major depressive episode).
Suicidal ideation during the past 3 months or suicidal behavior during the past 12 months.
Alcohol or substance use disorder within 2 years of screening.
MRI presence of cerebral vascular or other significant pathology.
History of transient ischemic attack or stroke within 12 months of screening
Seizure within 12 months of screening.
Severe head trauma or head trauma considered likely to be contributing to the subject's cognitive impairment.
Sleep apnea that is considered likely to be contributing to the subject's cognitive impairment.
Insufficiently controlled diabetes mellitus or hypertension.
Body mass index < 18.5 or > 37.5.
History or diagnosis of clinically significant cardiac disease
Currently or previously prescribed/administered aducanumab, lecanemab, or any anti-amyloid monoclonal antibody, more than 2 doses.

Name	Affiliation	Role
James Kupiec, MD	Cassava Sciences	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
MDFirst Research		Chandler	Arizona	85286	United States
CCT Research - Gilbert Neurology Partners

PubMed Identifier	Type	Citation	Retractions
41500915	Derived	Kupiec JW, Porsteinsson AP, Turner RS, Hendrix S, Mallinckrodt C, Khan A, Cohen I, Liss J, Clarnette R, Park KH, Hernandez AM, Burns LH. Phase 3 randomized clinical trials of simufilam in mild-to-moderate Alzheimer's disease. J Prev Alzheimers Dis. 2026 Mar;13(3):100469. doi: 10.1016/j.tjpad.2025.100469. Epub 2026 Jan 6.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 52 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 52 weeks at a dose of 100 mg.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 7, 2024	Apr 9, 2025

Masking Info

Arm/Group Information

ID	Title	Description
BG000	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 52 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 52 weeks at a dose of 100 mg.
BG001	Placebo	Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 52 weeks Placebo: Matching placebo given b.i.d. for 52 weeks.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00073.72± 7.911 BG00174.31± 7.555 BG00274.02± 7.737

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

<65 years

Title	Measurements
	BG00062 BG00147 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000225 BG001222 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00062 BG00151 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

American Indian or Alaska Native

Title	Measurements
	BG0000 BG0011 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Canada

Title	Measurements
	BG00031 BG00121 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in the 12-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12)

The change from baseline to Week 52 in the ADAS-Cog12, a psychometrician-administered battery comprised of several cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Scores range from 0 (best) to 80 (worst).

Data are from subjects in the Intent-to-treat population (all randomized subjects) who completed the assessment.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline (Study Day 1) to Week 52

ID	Title	Description
OG000	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 52 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 52 weeks at a dose of 100 mg.
OG001	Placebo	Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 52 weeks Placebo: Matching placebo given b.i.d. for 52 weeks.

Units	Counts
Participants	OG000306 OG001320

Title

Denominators

Categories

Title	Measurements
	OG0002.79± 0.363 OG0013.19± 0.359

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis		0.4308		Mean Difference (Final Values)	-0.39			2-Sided	95	-1.37	0.59					Superiority

Primary

Change From Baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)

The change from baseline to Week 52 in the ADCS-ADL, a 23-item study partner questionnaire that covers both basic activities of daily living (ADL) and more complex ADL or instrumental ADL. Scores range from 0 to 78, with a lower score indicating greater severity of functional loss.

Data are from subjects in the Intent-to-treat population (all randomized subjects) who completed the assessment.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline (Study Day 1) to Week 52

ID	Title	Description
OG000	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 52 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 52 weeks at a dose of 100 mg.
OG001	Placebo	Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 52 weeks Placebo: Matching placebo given b.i.d. for 52 weeks.

Secondary

Change From Baseline in the Integrated Alzheimer's Disease Rating Scale (iADRS)

The change from baseline to Week 52 in the iADRS, where scores range from 0 to 146 with lower scores indicating worse performance.

Data are from subjects in the Intent-to-treat population (all randomized subjects) who completed the assessment.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline (Study Day 1) to Week 52

ID	Title	Description
OG000	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 52 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 52 weeks at a dose of 100 mg.
OG001	Placebo	Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 52 weeks Placebo: Matching placebo given b.i.d. for 52 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in the Neuropsychiatric Inventory (NPI)

The change from baseline to Week 52 in the NPI, a 12-item study partner interview, which records the frequency and severity of common neuropsychiatric symptoms in dementia, as well as the level of study partner distress due to each of the neuropsychiatric problems. Scores range from 0 to 144, with higher scores indicating more frequent and severe symptoms, and greater levels of partner distress.

Data are from subjects in the Intent-to-treat population (all randomized subjects) who completed the assessment.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline (Study Day 1) to Week 52

ID	Title	Description
OG000	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 52 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 52 weeks at a dose of 100 mg.
OG001	Placebo	Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 52 weeks Placebo: Matching placebo given b.i.d. for 52 weeks.

Secondary

Change From Baseline in the Mini-Mental State Exam (MMSE)

The change from baseline to Week 52 in the MMSE, a set of standardized questions covering several target areas: orientation, registration, attention and calculation, short-term verbal recall, naming, repetition, 3-step command, reading, writing, and visuospatial cognitive assessment. Scores range from 0 to 30, lower scores indicate more severe impairment.

Data are from subjects in the Intent-to-treat population (all randomized subjects) who completed the assessment.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline (Study Day 1) to Week 52

ID	Title	Description
OG000	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 52 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 52 weeks at a dose of 100 mg.
OG001	Placebo	Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 52 weeks Placebo: Matching placebo given b.i.d. for 52 weeks.

Secondary

Change From Baseline in the Clinical Dementia Rating Sum of Boxes (CDR-SB)

The change from baseline to Week 52 in the CDR-SB, which characterizes 6 domains of cognitive and functional performance applicable to AD and related dementias: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Scores for each domain have a minimum of 0 and a maximum of 3, and the 6 domain scores are summed to give the CDR-SB, which has a minimum score of 0 and a maximum score of 18. Higher scores indicate more severe impairment.

Data are from subjects in the Intent-to-treat population (all randomized subjects) who completed the assessment.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline (Study Day 1) to Week 52

ID	Title	Description
OG000	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 52 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 52 weeks at a dose of 100 mg.
OG001	Placebo	Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 52 weeks Placebo: Matching placebo given b.i.d. for 52 weeks.

Secondary

Change From Baseline in the Zarit Burden Interview (ZBI)

The change from baseline to Week 52 in the ZBI, a 22-item study partner questionnaire designed to assess the stress or burden experienced by caregivers of people with dementia. Scores range from 0 to 88, with a higher score indicating greater stress or burden.

Data are from subjects in the Intent-to-treat population (all randomized subjects) who completed the assessment.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline (Study Day 1) to Week 52

ID	Title	Description
OG000	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 52 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 52 weeks at a dose of 100 mg.
OG001	Placebo	Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 52 weeks Placebo: Matching placebo given b.i.d. for 52 weeks.

Units	Counts

Other Pre-specified

Changes From Baseline in Plasma Biomarkers

Change from baseline in the following plasma biomarkers of AD pathology, neurodegeneration, and neuroinflammation: phospho-tau217 (P-tau217), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and total tau.

The overall number of participants analyzed is the number of participants who consented to take part in the biomarker analysis substudy and for whom there were baseline values for each biomarker. Plasma samples were not obtained from the whole substudy population at Week 52.

Posted

Mean

Standard Deviation

pg/mL

Baseline (Study Day 1) to Week 52

ID	Title	Description
OG000	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 52 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 52 weeks at a dose of 100 mg.
OG001	Placebo	Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 52 weeks Placebo: Matching placebo given b.i.d. for 52 weeks.

Other Pre-specified

Changes From Baseline in the Plasma SavaDx Biomarker

Change from baseline in SavaDx, a novel plasma biomarker

Change from baseline in SavaDx, a novel plasma biomarker, was included in the protocol as part of the secondary analysis as a biomarker which may have been measured. The final SAP, which postdated the protocol, included the analysis of biomarkers as an exploratory/tertiary endpoint. However, analysis of SavaDx was not conducted due to a sponsor decision and therefore, no results are available.

Posted

Baseline (Study Day 1) to Week 52

ID	Title	Description
OG000	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 52 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 52 weeks at a dose of 100 mg.
OG001	Placebo	Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 52 weeks Placebo: Matching placebo given b.i.d. for 52 weeks.

Units

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 52 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 52 weeks at a dose of 100 mg.	1	399	52	399	161	399
EG001	Placebo	Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 52 weeks Placebo: Matching placebo given b.i.d. for 52 weeks.	3	398	36	398	140	398

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hip fracture	Injury, poisoning and procedural complications	MedDRA v24.0	Systematic Assessment	EG0007 events7 affected399 at risk EG0011 events1 affected398 at risk
Fall	Injury, poisoning and procedural complications	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected399 at risk EG0012 events2 affected398 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0011 events1 affected398 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0011 events1 affected398 at risk
Cervical vertebral fracture	Injury, poisoning and procedural complications	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Craniocerebral injury	Injury, poisoning and procedural complications	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Post procedural hypotension	Injury, poisoning and procedural complications	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Syncope	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0004 events4 affected399 at risk EG0012 events2 affected398 at risk
Cerebral infarction	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0011 events1 affected398 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0012 events2 affected398 at risk
Presyncope	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0012 events2 affected398 at risk
Amyotrophic lateral sclerosis	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Cerebral artery occlusion	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Cervical radiculopathy	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Hyponatraemic encephalopathy	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Metabolic encephalopathy	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Partial seizures	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Seizure	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Thalamic infarction	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Urinary tract infection	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected399 at risk EG0013 events3 affected398 at risk
COVID-19	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0003 events3 affected399 at risk EG0011 events1 affected398 at risk
Pneumonia	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected399 at risk EG0012 events2 affected398 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected399 at risk EG0010 events0 affected398 at risk
Influenza	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0011 events1 affected398 at risk
Diverticulitis	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Norovirus infection	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Pneumonia viral	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Pyelonephritis	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Atrial fibrillation	Cardiac disorders	MedDRA v24.0	Systematic Assessment	EG0003 events3 affected399 at risk EG0010 events0 affected398 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Angina pectoris	Cardiac disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Bradycardia	Cardiac disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Cardiac arrest	Cardiac disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Sinus arrest	Cardiac disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Sinus node dysfunction	Cardiac disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Ventricular extrasystoles	Cardiac disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Colitis	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0011 events1 affected398 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Constipation	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Gastrointestinal inflammation	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Intestinal ischaemia	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Pancreatic duct dilatation	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Pancreatic mass	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Stomach mass	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Vomiting	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0011 events1 affected398 at risk
Adenocarcinoma pancreas	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Clear cell renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Neuroendocrine carcinoma of the bladder	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Prostate cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Asthenia	General disorders	MedDRA v24.0	Systematic Assessment	EG0004 events4 affected399 at risk EG0011 events1 affected398 at risk
Death	General disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Non-cardiac chest pain	General disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Pyrexia	General disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Delirium	Psychiatric disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected399 at risk EG0010 events0 affected398 at risk
Aggression	Psychiatric disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Anxiety	Psychiatric disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Confusional state	Psychiatric disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Hallucination	Psychiatric disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Paranoia	Psychiatric disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected399 at risk EG0013 events2 affected398 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Failure to thrive	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Blood phosphorus decreased	Investigations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Lipase increased	Investigations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Magnetic resonance imaging hepatobiliary abnormal	Investigations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Amaurosis fugax	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Retinal detachment	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Hypotension	Vascular disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk
Internal haemorrhage	Vascular disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected399 at risk EG0010 events0 affected398 at risk
Haematuria	Renal and urinary disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected399 at risk EG0011 events1 affected398 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
COVID-19	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG00029 events29 affected399 at risk EG00136 events35 affected398 at risk
Urinary tract infection	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG00034 events29 affected399 at risk EG00135 events27 affected398 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG00013 events11 affected399 at risk EG0018 events8 affected398 at risk
Headache	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG00019 events18 affected399 at risk EG00114 events11 affected398 at risk
Dizziness	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG00023 events21 affected399 at risk EG0011 events1 affected398 at risk
Fall	Injury, poisoning and procedural complications	MedDRA v24.0	Systematic Assessment	EG00038 events30 affected399 at risk EG00135 events28 affected398 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG00017 events16 affected399 at risk EG00116 events16 affected398 at risk
Constipation	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG00012 events11 affected399 at risk EG0018 events8 affected398 at risk
Nausea	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG00011 events10 affected399 at risk EG0015 events5 affected398 at risk
Weight decreased	Investigations	MedDRA v24.0	Systematic Assessment	EG0006 events6 affected399 at risk EG00110 events10 affected398 at risk
Anxiety	Psychiatric disorders	MedDRA v24.0	Systematic Assessment	EG00014 events14 affected399 at risk EG00111 events9 affected398 at risk
Depression	Psychiatric disorders	MedDRA v24.0	Systematic Assessment	EG00010 events10 affected399 at risk EG00111 events11 affected398 at risk
Agitation	Psychiatric disorders	MedDRA v24.0	Systematic Assessment	EG0009 events9 affected399 at risk EG0015 events5 affected398 at risk
Fatigue	General disorders	MedDRA v24.0	Systematic Assessment	EG00011 events11 affected399 at risk EG00111 events11 affected398 at risk
Hypertension	Vascular disorders	MedDRA v24.0	Systematic Assessment	EG0008 events8 affected399 at risk EG0015 events5 affected398 at risk

ID	Term
D003704	Dementia
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D024801	Tauopathies
D019636	Neurodegenerative Diseases
D019965	Neurocognitive Disorders
D001523	Mental Disorders