Study Evaluating Intepirdine (RVT-101) in Subjects With M... | NCT02585934

Label	Type	Description	Intervention Names
RVT-101	Experimental	RVT-101 adjunct to 5 mg or 10 mg donepezil	Drug: RVT-101
Placebo	Placebo Comparator	Placebo adjunct to 5 mg or 10 mg donepezil	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
RVT-101	Drug	once daily, oral, 35 mg tablets	RVT-101
Placebo

Measure	Description	Time Frame
Alzheimer's Disease Assessment Scale - Cognitive Subscale 11 Items (ADAS-Cog-11) Score Change From Baseline to Week 24	The 11-item ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place, and spontaneous speech. The ADAS-Cog-11 total score range is from 0 to 70, with a higher score indicating more severe cognitive impairment.	Baseline, 24 weeks
Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Score Change From Baseline to Week 24	The ADCS-ADL scale measures functional impairment in terms of activities of daily living. The score ranges from 0 to 78. The lower the score, the greater the impairment; higher scores indicate better (more desirable) function	Baseline, 24 weeks

Measure	Description	Time Frame
Clinical Global Impression of Change - Plus Caregiver Interview (CIBIC+) Score at Week 24	The CIBIC+ assessment measures the global functioning of the subject. The CIBIC+ is scored as a seven-point categorical rating, ranging from a score of 1 (indicating "very much improved"), to a score of 4 (indicating "no change"), or to a score of 7 (indicating "very much worse.") Lower CIBIC+ scores indicate better (more desirable) function

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female subject with AD
Ongoing donepezil therapy for AD
An MMSE score 12 to 24 inclusive at Screening; MMSE score 10-26 inclusive at Baseline
Hachinski Ischaemia score less than or equal to 4 at Screening.
If female, subject must be: a. of non-childbearing potential or surgically sterile; or, b. willing to use an adequate methods of birth control. Male subjects who are sexually active will also be required to use an adequate form of birth control.
Subject has the ability to comply with procedures for cognitive and other testing in the opinion of the investigator.
Subject has a reliable caregiver who is willing to report on subject's status throughout the study.

Exclusion Criteria:

Other Causes for Dementia

Diagnosis of vascular dementia
Atypical clinical features or clinical course of dementia that would lead the investigator to conclude symptoms are more likely due to an alternate dementia diagnosis including, but not limited to, frontotemporal dementia, Lewy body dementia, or others.

Confounding Medical Conditions

History of significant psychiatric illness such as schizophrenia or bipolar affective disorder or any other significant psychiatric illness that in the opinion of the investigator would interfere with participation in the study;
Any clinically relevant concomitant disease, which, in the opinion of the investigator, makes the subject unsuitable for inclusion in the study.

Name	Affiliation	Role
Ilise Lombardo, MD	Axovant Sciences, Inc., Vice President, Clinical Research	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
US112		Phoenix	Arizona	85005	United States
US220

ID	Title	Description
FG000	RVT-101	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets for up to 27 weeks
FG001	Placebo	Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet for up to 27 weeks

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol: Protocol	Apr 13, 2016	Sep 12, 2018

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

Alzheimer's Disease Assessment Scale - Cognitive Subscale 11 Items (ADAS-Cog-11) Score Change From Baseline to Week 24

The 11-item ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place, and spontaneous speech. The ADAS-Cog-11 total score range is from 0 to 70, with a higher score indicating more severe cognitive impairment.

ITT Population with data at both timepoints.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, 24 weeks

ID	Title	Description
OG000	RVT-101	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets
OG001	Placebo	Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet

Units	Counts
Participants	OG000584 OG001577

Title

Denominators

Categories

Title	Measurements
	OG0000.39± 0.211 OG0010.75± 0.213

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	Statistical Method: Mixed model for repeated measures	0.2249	the threshold for statistical significance was p=0.05	least square mean difference	-0.36			2-Sided	95	-0.95	0.22					Superiority

Primary

Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Score Change From Baseline to Week 24

The ADCS-ADL scale measures functional impairment in terms of activities of daily living. The score ranges from 0 to 78. The lower the score, the greater the impairment; higher scores indicate better (more desirable) function

ITT Population with data at both endpoints

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, 24 weeks

ID	Title	Description
OG000	RVT-101	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets
OG001	Placebo	Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet

Units	Counts
Participants	OG000

Secondary

Clinical Global Impression of Change - Plus Caregiver Interview (CIBIC+) Score at Week 24

The CIBIC+ assessment measures the global functioning of the subject. The CIBIC+ is scored as a seven-point categorical rating, ranging from a score of 1 (indicating "very much improved"), to a score of 4 (indicating "no change"), or to a score of 7 (indicating "very much worse.") Lower CIBIC+ scores indicate better (more desirable) function

ITT population at the Week 24 timepoint

Posted

Least Squares Mean

Standard Error

units on a scale

24 weeks

ID	Title	Description
OG000	RVT-101	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets
OG001	Placebo	Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet

Units	Counts
Participants	OG000

Secondary

The Dependence Scale (DS) Score Change From Baseline to Week 24

The DS measures the amount of assistance patients with dementia require in performing daily activities. The scale consists of 13 items, representing a range of severity from mild to severe levels of dependency. The score range is from 0 to 15 with higher scores indicating greater dependency.

ITT population at both timepoints

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, 24 weeks

ID	Title	Description
OG000	RVT-101	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets
OG001	Placebo	Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet

Units	Counts
Participants	OG000

Secondary

Neuropsychiatric Inventory (NPI) Score Change From Baseline to Week 24

The NPI is a behavior rating scale composed of a 12-item structured interview of the caregiver that is scored from 0 to 144 (the higher the score, the greater the psychiatric disturbance). It assesses 12 behavioral disturbances occurring in dementia patients: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor activity, night-time behavior disturbances, and eating disturbances. Both the frequency and the severity of each behavior are determined.

ITT Population at both timepoints

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline and Week 24

ID	Title	Description
OG000	RVT-101	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets
OG001	Placebo	Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet

Units	Counts
Participants

Secondary

ADAS-Cog-13 Score Change From Baseline to Week 24

13-item ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place, and spontaneous speech. Most items are evaluated by tests, but some are dependent on clinician ratings on a 5-point scale. The ADAS-Cog-13 is the ADAS-Cog-11 with 2 additional items: delayed word recall and total digit cancellation. Scores for the ADAS-Cog-13 range from 0 to 85 with higher scores indicating greater dysfunction.

ITT at both timepoints

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, 24 weeks

ID	Title	Description
OG000	RVT-101	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets
OG001	Placebo	Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet

Units	Counts
Participants	OG000

Secondary

Measurement of Concentrations of RVT-101 (Intepirdine) in Plasma

Measurement collected at timepoints Week 6, Week 12, Week 18, and Week 24

PK population at specified timepoints: Week 6, Week 12, Week 18, and Week 24

Posted

Geometric Mean

95% Confidence Interval

ng/mL

Week 6, Week 12, Week 18, Week 24

ID	Title	Description
OG000	RVT-101	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets for up to 27 weeks

Units	Counts
Participants	OG000656

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	RVT-101 Treatment	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets for up to 27 weeks	3	656	40	656	191	656
EG001	Placebo Treatment	Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet for up to 27 weeks	2	651	44	651	166	651
EG002	Screening Period	Participants screened (0-4 weeks) prior to entering to the first dose of single-blind study medication (ie, prior to the Run-In period)	1	2,173	12	2,173	0	2,173
EG003	Run-In Period	Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet (for 3 weeks)	1	1,470	14	1,470	0	1,470
EG004	RVT-101 Post-Treatment	Subjects reported adverse events after completing the treatment period. The Post-Treatment period - defined as up to 30 days post-last-dose	0	656	3	656	0	656
EG005	Placebo Post-Treatment	Subjects reported adverse events after completing the treatment period. The Post-Treatment period - defined as up to 30 days post-last-dose	1	651	3	651	0	651

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Cerebrovascular Accident	Nervous system disorders	Systematic Assessment	EG0000 affected656 at risk EG0013 affected651 at risk EG0020 affected2,173 at risk EG0030 affected1,470 at risk EG0040 affected656 at risk EG0050 affected651 at risk
Syncope	Nervous system disorders	Systematic Assessment	EG0002 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Transient ischaemic attack	Nervous system disorders	Systematic Assessment	EG0002 affected656 at risk EG0011 affected651 at risk EG0021 affected2,173 at risk EG003
Ischaemic stroke	Nervous system disorders	Systematic Assessment	EG0002 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Seizure	Nervous system disorders	Systematic Assessment	EG0000 affected656 at risk EG0012 affected651 at risk EG0020 affected2,173 at risk EG003
Dementia	Nervous system disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Dizziness	Nervous system disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Headache	Nervous system disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Hypoxic-ischaemic encephalopathy	Nervous system disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Lethargy	Nervous system disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Status epilepticus	Nervous system disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0002 affected656 at risk EG0013 affected651 at risk EG0020 affected2,173 at risk EG003
Acoustic neuroma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Hepatocellular carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Lung neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0021 affected2,173 at risk EG003
Meningioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Ovarian cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Myocardial infarction	Cardiac disorders	Systematic Assessment	EG0001 affected656 at risk EG0012 affected651 at risk EG0020 affected2,173 at risk EG003
Atrial Fibrillation	Cardiac disorders	Systematic Assessment	EG0001 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Angina pectoris	Cardiac disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Angina unstable	Cardiac disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Atrioventricular block	Cardiac disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0021 affected2,173 at risk EG003
Cardiac arrest	Cardiac disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Cardiac failure congestive	Cardiac disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Cardio-respiratory arrest	Cardiac disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Mitral valve prolapse	Cardiac disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Pericardial effusion	Cardiac disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Right ventricular failure	Cardiac disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Sinus node dysfunction	Cardiac disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Diverticulitis	Infections and infestations	Systematic Assessment	EG0002 affected656 at risk EG0012 affected651 at risk EG0020 affected2,173 at risk EG003
Pneumonia	Infections and infestations	Systematic Assessment	EG0002 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Urinary tract infection	Infections and infestations	Systematic Assessment	EG0001 affected656 at risk EG0011 affected651 at risk EG0021 affected2,173 at risk EG003
Appendicitis	Infections and infestations	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Cellulitis	Infections and infestations	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Gastroenteritis	Infections and infestations	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Fall	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 affected656 at risk EG0013 affected651 at risk EG0021 affected2,173 at risk EG003
Hip fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 affected656 at risk EG0013 affected651 at risk EG0022 affected2,173 at risk EG003
Contusion	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0021 affected2,173 at risk EG003
Patella fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Pelvic fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Stoma obstruction	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Subdural haematoma	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Upper limb fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Wrist fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Duodenal vascular ectasia	Gastrointestinal disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Proctitis	Gastrointestinal disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Aggression	Psychiatric disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Delirium	Psychiatric disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Mental status changes	Psychiatric disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Mood altered	Psychiatric disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Psychotic disorder	Psychiatric disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Somatic symptom disorder	Psychiatric disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0021 affected2,173 at risk EG003
Chest pain	General disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Hypothermia	General disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Non-cardiac chest pain	General disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Inner ear disorder	Ear and labyrinth disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Vertigo positonal	Ear and labyrinth disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Bile duct stone	Hepatobiliary disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Cholecystitis	Hepatobiliary disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Hypertension	Vascular disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Poor peripheral circulation	Vascular disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Haemoglobin decreased	Investigations	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected656 at risk EG0011 affected651 at risk EG0020 affected2,173 at risk EG003
Acute kidney injury	Renal and urinary disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Benign prostatic hyperplasia	Reproductive system and breast disorders	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Humerus fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected656 at risk EG0010 affected651 at risk EG0021 affected2,173 at risk EG003
Cardiac failure	Cardiac disorders	Systematic Assessment	EG0000 affected656 at risk EG0010 affected651 at risk EG0021 affected2,173 at risk EG003
Anaemia	Blood and lymphatic system disorders	Systematic Assessment	EG0000 affected656 at risk EG0010 affected651 at risk EG0021 affected2,173 at risk EG003
Volvulus	Gastrointestinal disorders	Systematic Assessment	EG0000 affected656 at risk EG0010 affected651 at risk EG0021 affected2,173 at risk EG003
lower respiratory tract infection	Infections and infestations	Systematic Assessment	EG0001 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Infected bite	Infections and infestations	Systematic Assessment	EG0000 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Foot fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Pubis fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Agitation	Psychiatric disorders	Systematic Assessment	EG0000 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Pneumothorax spontaneous	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Asthenia	General disorders	Systematic Assessment	EG0000 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Dehydration	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Hydrocephalus	Nervous system disorders	Systematic Assessment	EG0000 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Gait disturbance	General disorders	Systematic Assessment	EG0000 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
Sepsis	Infections and infestations	Systematic Assessment	EG0000 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003
invasive ductal breast carcinoma	Reproductive system and breast disorders	Systematic Assessment	EG0000 affected656 at risk EG0010 affected651 at risk EG0020 affected2,173 at risk EG003

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Fall	Injury, poisoning and procedural complications	Systematic Assessment	EG00037 affected656 at risk EG00129 affected651 at risk EG0020 affected2,173 at risk EG0030 affected1,470 at risk EG0040 affected656 at risk EG0050 affected651 at risk
Urinary tract infection	Infections and infestations	Systematic Assessment	EG00025 affected656 at risk EG00126 affected651 at risk EG0020 affected2,173 at risk EG003
Nasopharyngitis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00023 affected656 at risk EG00119 affected651 at risk EG0020 affected2,173 at risk EG003
Headache	Nervous system disorders	Systematic Assessment	EG00017 affected656 at risk EG00118 affected651 at risk EG0020 affected2,173 at risk EG003
Dizziness	Nervous system disorders	Systematic Assessment	EG00019 affected656 at risk EG00112 affected651 at risk EG0020 affected2,173 at risk EG003
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG00013 affected656 at risk EG00117 affected651 at risk EG0020 affected2,173 at risk EG003
Nausea	Gastrointestinal disorders	Systematic Assessment	EG00017 affected656 at risk EG00113 affected651 at risk EG0020 affected2,173 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG00011 affected656 at risk EG00115 affected651 at risk EG0020 affected2,173 at risk EG003
Bronchitis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00014 affected656 at risk EG00110 affected651 at risk EG0020 affected2,173 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00015 affected656 at risk EG0017 affected651 at risk EG0020 affected2,173 at risk EG003

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

ID	Title	Description
BG000	RVT-101	RVT-101 adjunct to 5 mg or 10 mg donepezil RVT-101: once daily, oral, 35 mg tablets for up to 27 weeks
BG001	Placebo	Placebo adjunct to 5 mg or 10 mg donepezil Placebo: once daily, oral, pill manufactured to match RVT-101 35 mg tablet for up to 27 weeks
BG002	Total	Total of all reporting groups