A Long-Term Safety And Tolerability Extension Study Of Ba... | NCT00998764

ID	Type	Description	Link
B2521004	Other Identifier	Alias Study Number
2009-015080-13	EudraCT Number

A Long-Term Safety And Tolerability Extension Study Of Ba... | NCT00998764 | Trialant

Arms/Interventions Module

Label	Type	Description	Intervention Names
Bapineuzumab 0.5 mg/kg	Experimental		Drug: Bapineuzumab 0.5 mg/kg

Name	Type	Description	Arm Group Labels	Other Names
Bapineuzumab 0.5 mg/kg	Drug	I.V., 0.5 mg/kg, infusion every 13 weeks for a total of 16 infusions.	Bapineuzumab 0.5 mg/kg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants Reporting a Serious Adverse Event	Safety was measured according to standard adverse event collection as described in the Adverse Event Section of the Results. Complete tables of events are provided there.	Up to Week 195

Secondary Outcomes

Measure	Description	Time Frame
Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78	The ADAS-Cog is a multi-item, objective measure of cognitive function. The scale evaluates memory, language, and praxis with items such as orientation, word recall, word recognition, object identification, comprehension, and the completion of simple tasks. Analysis of the ADAS-Cog for this study was based upon an 11 item score from the following items 1) word recall task, 2) naming objects and fingers, 3) following commands, 4)constructional praxis, 5) ideational praxis, 6) orientation, 7) word recognition, 8 remembering test instructions, 9) spoken language ability, 10) word finding difficulty in spontaneous speech, and 11) comprehension.This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced. The ADAS-Cog/11 ranged from 0 to 70 points, with higher scores indicating a greater degree of impairment. A negative change from baseline indicates a decrease in cognitive impairment.

Contacts/Locations Module

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University Of Alabama at Birmingham		Birmingham	Alabama	35249	United States
UAB Center for Psychiatric Medicine

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
27334799	Derived	Ivanoiu A, Pariente J, Booth K, Lobello K, Luscan G, Hua L, Lucas P, Styren S, Yang L, Li D, Black RS, Brashear HR, McRae T. Long-term safety and tolerability of bapineuzumab in patients with Alzheimer's disease in two phase 3 extension studies. Alzheimers Res Ther. 2016 Jun 23;8(1):24. doi: 10.1186/s13195-016-0193-y.

Label	URL
To obtain contact information for a study center near you, click here.	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo/Bapineuzumab	Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by intravenous (IV) infusion approximately every 13 weeks up to week 195.
FG001	Bapineuzumab/Bapineuzumab

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Comment	Reasons
Lack of Efficacy		FG0003 subjects FG0016 subjects
Adverse Event		FG00017 subjects FG00112 subjects
Withdrawal by Subject		FG00019 subjects FG00125 subjects
Physician Decision		FG0003 subjects FG0013 subjects
Death		FG0003 subjects FG0011 subjects
Discontinuation of Study by Sponsor		FG000164 subjects FG001217 subjects
Protocol Violation		FG0000 subjects FG0011 subjects
Failed to Return		FG0001 subjects FG0011 subjects
Lost to Follow-up		FG0001 subjects FG0011 subjects
Loss of Caregiver		FG0000 subjects FG0013 subjects
Other		FG0004 subjects FG0014 subjects
Recurrent Episode of vasogenic edema		FG0001 subjects FG0010 subjects

Arm/Group Information

ID	Title	Description
BG000	Placebo/Bapineuzumab	Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study Bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
BG001	Bapineuzumab/Bapineuzumab	Participants received Bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
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
	BG00071.4± 8.14 BG00172.1± 7.47 BG00271.8± 7.77

Age, Customized

Number

Participants

Title

Denominators

Categories

< 65 years

Title	Measurements
	BG00044 BG00142 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000135 BG001186 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

Number of Participants Reporting a Serious Adverse Event

Safety was measured according to standard adverse event collection as described in the Adverse Event Section of the Results. Complete tables of events are provided there.

Safety population

Posted

Number

Number of Participants

Up to Week 195

ID	Title	Description
OG000	Placebo/Bapineuzumab	Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
OG001	Bapineuzumab/Bapineuzumab	Participants received bapineuzumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.

Units	Counts
Participants	OG000215 OG001275

Title

Denominators

Categories

Title	Measurements
	OG00035 OG00133

Secondary

Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78

The ADAS-Cog is a multi-item, objective measure of cognitive function. The scale evaluates memory, language, and praxis with items such as orientation, word recall, word recognition, object identification, comprehension, and the completion of simple tasks. Analysis of the ADAS-Cog for this study was based upon an 11 item score from the following items 1) word recall task, 2) naming objects and fingers, 3) following commands, 4)constructional praxis, 5) ideational praxis, 6) orientation, 7) word recognition, 8 remembering test instructions, 9) spoken language ability, 10) word finding difficulty in spontaneous speech, and 11) comprehension.This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced. The ADAS-Cog/11 ranged from 0 to 70 points, with higher scores indicating a greater degree of impairment. A negative change from baseline indicates a decrease in cognitive impairment.

The Modified Intent-to-Treat (mITT) Population was defined as all randomly assigned participants who received investigational product in the base study, had a baseline for the base study, had at least one valid post-baseline assessment of the ADAS-Cog and DAD total score in the base study and signed informed consent in the extension study.

Posted

Least Squares Mean

Standard Error

Units on a scale

Base Study Baseline, Weeks 13, 26, 39, 52 and 78

ID	Title	Description
OG000	Placebo/Bapineuzumab	Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.

Secondary

Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.

The ADAS-Cog is a multi-item, objective measure of cognitive function. The scale evaluates memory, language, and praxis with items such as orientation, word recall, word recognition, object identification, comprehension, and the completion of simple tasks. Analysis of the ADAS-Cog for this study was based upon an 11 item score from the following items 1) word recall task, 2) naming objects and fingers, 3) following commands, 4)constructional praxis, 5) ideational praxis, 6) orientation, 7) word recognition, 8)remembering test instructions, 9) spoken language ability, 10) word finding difficulty in spontaneous speech, and 11) comprehension.This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced. The ADAS-Cog/11 ranged from 0 to 70 points, with higher scores indicating a greater degree of impairment. A negative change from baseline indicates a decrease in cognitive impairment.

Posted

Least Squares Mean

Standard Error

Units on a scale

Base Study Baseline, Weeks 13, 26, 39, 52 and 78

ID	Title	Description
OG000	Placebo/Bapineuzumab	Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.

Secondary

Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.

The DAD measures instrumental and basic activities of daily living in AD participants. The DAD is administered to the participant's caregiver in the form of an interview. The performance of basic activities of daily living is evaluated in 10 aspects including hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. The caregiver answers 40 questions as yes, no, or not applicable. A one-point score was assigned to each question if the answer is "yes" and a zero score was assigned if the answer is "no". For questions answered as "not applicable", no score will be assigned. The DAD total score was calculated as the total number of questions answered as "yes" divided by the total number of questions answered as "yes" or "no", times 100. The DAD score can range from 0 to 100, with higher scores indicating better function. A positive change indicates improvement from baseline.

Posted

Least Squares Mean

Standard Error

Units on a scale

Base Study Baseline, Weeks 13, 26, 39, 52 and 78

ID	Title	Description
OG000	Placebo/Bapineuzumab	Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.

Secondary

Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.

Posted

Least Squares Mean

Standard Error

Units on scale

Base Study Baseline, Weeks 13, 26, 39, 52 and 78

ID	Title	Description
OG000	Placebo/Bapineuzumab	Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.

Secondary

Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.

NPI:12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/ aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/ indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, nighttime behavior. Severity(1=Mild to 3=Severe),frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency*severity=each domain score(range 0-12). The NPI total score ranges from 0 to 144 with higher NPI scores indicate greater impairment. A negative change indicates improvement from baseline.

Posted

Least Squares Mean

Standard Error

Units on a scale

Base Study Baseline, Weeks 26, 52 and 78

ID	Title	Description
OG000	Placebo/Bapineuzumab	Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
OG001	Bapinezumab/Bapinezumab	Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.

Secondary

Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.

Posted

Least Squares Mean

Standard Error

Units on a scale

Base Study Baseline, Weeks 26, 52 and 78

ID	Title	Description
OG000	Placebo/Bapineuzumab	Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
OG001	Bapinezumab/Bapinezumab	Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.

Secondary

Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.

MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. The MMSE total score can range from 0 to 30, with lower scores indicating a greater degree of impairment. A positive change indicates improvement from baseline.

Posted

Least Squares Mean

Standard Error

Units on a scale

Base Study Baseline, Weeks 6, 19, 32, 45 and 78

ID	Title	Description
OG000	Placebo/Bapineuzumab	Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
OG001	Bapinezumab/Bapinezumab	Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.

Secondary

Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.

Posted

Least Squares Mean

Standard Error

Units on a scale

Base Study Baseline, Weeks 6, 19, 32, 45 and 78

ID	Title	Description
OG000	Placebo/Bapineuzumab	Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
OG001	Bapinezumab/Bapinezumab	Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.

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	Placebo/Bapineuzumab	Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.			35	215	57	215
EG001	Bapineuzumab/Bapineuzumab	Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.			33	275	45	275

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Aortic valve stenosis	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Atrial flutter	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Atrioventricular block	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Cardiac failure	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0011 events1 affected275 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0011 events1 affected275 at risk
Cardiomyopathy	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Mitral valve disease	Cardiac disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0002 events2 affected215 at risk EG0010 events0 affected275 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Asthenia	General disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0014 events4 affected275 at risk
Asthenia	General disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Chest pain	General disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Gait disturbance	General disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
General physical health deterioration	General disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 15.0	Non-systematic Assessment	EG0002 events1 affected215 at risk EG0010 events0 affected275 at risk
Hepatic steatosis	Hepatobiliary disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Bronchitis	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Gastritis viral	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Peritonsillar abscess	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Pneumonia	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Urinary tract infection	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG0002 events2 affected215 at risk EG0011 events1 affected275 at risk
Alcohol poisoning	Injury, poisoning and procedural complications	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Forearm fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Traumatic intracranial haemorrhage	Injury, poisoning and procedural complications	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Wrist fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Blood creatinine increased	Investigations	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Metastases to lymph nodes	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Metastases to peritoneum	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Ovarian cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Cerebellar infarction	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Cerebral infarction	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Cerebral microhaemorrhage	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0002 events2 affected215 at risk EG0010 events0 affected275 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Convulsion	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0012 events2 affected275 at risk
Epilepsy	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0003 events3 affected215 at risk EG0010 events0 affected275 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0011 events1 affected275 at risk
Lacunar infarction	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Lumbar radiculopathy	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Multiple system atrophy	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Partial seizures	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Presyncope	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0010 events0 affected275 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0002 events2 affected215 at risk EG0010 events0 affected275 at risk
Vasogenic cerebral oedema	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0006 events6 affected215 at risk EG0012 events2 affected275 at risk
Aggression	Psychiatric disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0012 events2 affected275 at risk
Agitation	Psychiatric disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected215 at risk EG0012 events2 affected275 at risk
Confusional state	Psychiatric disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0012 events2 affected275 at risk
Delusion	Psychiatric disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Hallucination	Psychiatric disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Mental status changes	Psychiatric disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Mood swings	Psychiatric disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Suicidal ideation	Psychiatric disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Incontinence	Renal and urinary disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk
Peripheral artery stenosis	Vascular disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected215 at risk EG0011 events1 affected275 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 15.0	Non-systematic Assessment	EG00012 events12 affected215 at risk EG00113 events10 affected275 at risk
Cerebral microhaemorrhage	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG00022 events18 affected215 at risk EG00116 events15 affected275 at risk
Headache	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG00029 events16 affected215 at risk EG0018 events8 affected275 at risk
Vasogenic cerebral oedema	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG00024 events17 affected215 at risk EG0018 events8 affected275 at risk
Anxiety	Psychiatric disorders	MedDRA 15.0	Non-systematic Assessment	EG00013 events11 affected215 at risk EG0017 events7 affected275 at risk

Ancestor Terms

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

Title

Denominators

Categories

Week 13 (N= 197, 253)

Title	Measurements
	OG0005.53± 0.57 OG0016.28± 0.50

Week 26 (N = 154, 221)

Title	Measurements
	OG0007.41± 0.63 OG0017.70± 0.54

Week 39 (N = 121, 184)

Title	Measurements
	OG0008.83± 0.72 OG0018.87± 0.61

Week 52 (N = 91, 139)

Title	Measurements
	OG00010.12± 0.75 OG00110.11± 0.63

Week 78 (N = 52, 80)

Title	Measurements
	OG00013.91± 0.96 OG00112.70± 0.80

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	Change from baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog) at week 13	Mixed Models Analysis	0.324	Mean Difference (Final Values)	0.74	2-Sided	95	-0.74	2.23	No	Superiority or Other
OG000 OG001	Change from baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog) at week 26	Mixed Models Analysis	0.723	Mean Difference (Final Values)	0.29	2-Sided	95	-1.33	1.92	No	Superiority or Other
OG000 OG001	Change from baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog) at week 39	Mixed Models Analysis	0.966	Mean Difference (Final Values)	0.04	2-Sided	95	-1.81	1.89	No	Superiority or Other
OG000 OG001	Change from baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog) at week 52	Mixed Models Analysis	0.996	Mean Difference (Final Values)	0.00	2-Sided	95	-1.93	1.92	No	Superiority or Other
OG000 OG001	Change from baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog) at week 78	Mixed Models Analysis	0.336	Mean Difference (Final Values)	-1.21	2-Sided	95	-3.67	1.26	No	Superiority or Other

Title

Denominators

Categories

Week 13 (N = 197, 253)

Title	Measurements
	OG0000.89± 0.36 OG0010.73± 0.32

Week 26 (N = 154, 221)

Title	Measurements
	OG0002.87± 0.42 OG0012.19± 0.35

Week 39 (N = 121, 184)

Title	Measurements
	OG0004.26± 0.50 OG0013.35± 0.42

Week 52 (N = 91, 139)

Title	Measurements
	OG0005.42± 0.55 OG0014.51± 0.45

Week 78 (N = 52, 80)

Title	Measurements
	OG0009.21± 0.82 OG0017.07± 0.66

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	Change from extension study baseline in ADAS-Cog at week 13	Mixed Models Analysis	0.737	Mean Difference (Final Values)	-0.16	2-Sided	95	-1.11	0.79	No	Superiority or Other
OG000 OG001	Change from extension study baseline in ADAS-Cog at week 26	Mixed Models Analysis	0.213	Mean Difference (Final Values)	-0.68	2-Sided	95	-1.76	0.40	No	Superiority or Other
OG000 OG001	Change from extension study baseline in ADAS-Cog at week 39	Mixed Models Analysis	0.168	Mean Difference (Final Values)	-0.90	2-Sided	95	-2.19	0.38	No	Superiority or Other
OG000 OG001	Change from extension study baseline in ADAS-Cog at week 52	Mixed Models Analysis	0.197	Mean Difference (Final Values)	-0.91	2-Sided	95	-2.30	0.48	No	Superiority or Other
OG000 OG001	Change from extension study baseline in ADAS-Cog at week 78	Mixed Models Analysis	0.044	Mean Difference (Final Values)	-2.13	2-Sided	95	-4.21	0.06	No	Superiority or Other

Title

Denominators

Categories

Week 13 (N = 194, 247)

Title	Measurements
	OG000-12.33± 1.27 OG00115.32± 1.11

Week 26 (N = 151, 222)

Title	Measurements
	OG000-15.37± 1.29 OG001-18.04± 1.11

Week 39 (N = 119, 180)

Title	Measurements
	OG000-17.74± 1.47 OG001-21.33± 1.24

Week 52 (N = 89, 137)

Title	Measurements
	OG000-20.96± 1.65 OG001-22.72± 1.36

Week 78 (N = 50, 81)

Title	Measurements
	OG000-26.33± 2.18 OG001-29.11± 1.75

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	Change from base study baseline in DAD score at Week 13	Mixed Models Analysis	0.077	Mean Difference (Final Values)	-2.99	2-Sided	95	-6.30	0.33	No	Superiority or Other
OG000 OG001	Change from base study baseline in DAD score at Week 26	Mixed Models Analysis	0.117	Mean Difference (Final Values)	-2.67	2-Sided	95	-6.02	0.67	No	Superiority or Other
OG000 OG001	Change from base study baseline in DAD score at Week 39	Mixed Models Analysis	0.063	Mean Difference (Final Values)	-3.60	2-Sided	95	-7.38	0.19	No	Superiority or Other
OG000 OG001	Change from base study baseline in DAD score at Week 52	Mixed Models Analysis	0.412	Mean Difference (Final Values)	-1.75	2-Sided	95	-5.95	2.44	No	Superiority or Other
OG000 OG001	Change from base study baseline in DAD score at Week 78	Mixed Models Analysis	0.321	Mean Difference (Final Values)	-2.78	2-Sided	95	-8.28	2.73	No	Superiority or Other

Title

Denominators

Categories

Week 13 (N = 194, 247)

Title	Measurements
	OG000-2.63± 0.83 OG001-3.71± 0.73

Week 26 (N = 151, 222)

Title	Measurements
	OG000-5.76± 1.01 OG001-6.46± 0.86

Week 39 (N = 119, 180)

Title	Measurements
	OG000-8.17± 1.22 OG001-9.72± 1.02

Week 52 (N = 89, 137)

Title	Measurements
	OG000-11.82± 1.34 OG001-11.11± 1.10

Week 78 (N = 50, 81)

Title	Measurements
	OG000-17.34± 1.94 OG001-17.48± 1.56

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	Change from extension study baseline in DAD score at Week 13	Mixed Models Analysis	0.329	Mean Difference (Final Values)	-1.08	2-Sided	95	-3.24	1.09	No	Superiority or Other
OG000 OG001	Change from extension study baseline in DAD score at Week 26	Mixed Models Analysis	0.601	Mean Difference (Final Values)	-0.70	2-Sided	95	-3.31	1.92	No	Superiority or Other
OG000 OG001	Change from extension study baseline in DAD score at Week 39	Mixed Models Analysis	0.328	Mean Difference (Final Values)	-1.55	2-Sided	95	-4.67	1.56	No	Superiority or Other
OG000 OG001	Change from extension study baseline in DAD score at Week 52	Mixed Models Analysis	0.680	Mean Difference (Final Values)	0.71	2-Sided	95	-2.70	4.13	No	Superiority or Other
OG000 OG001	Change from extension study baseline in DAD score at Week 78	Mixed Models Analysis	0.954	Mean Difference (Final Values)	-0.14	2-Sided	95	-5.05	4.77	No	Superiority or Other

Title

Denominators

Categories

Week 26 (N = 176, 240)

Title	Measurements
	OG0002.84± 0.97 OG0012.95± 0.83

Week 52 (N = 110, 163)

Title	Measurements
	OG0004.32± 0.96 OG0013.52± 0.80

Week 78 (N = 51, 81)

Title	Measurements
	OG0006.95± 1.70 OG0014.93± 1.36

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	Change from base study baseline in NPI score at week 26.	Mixed Models Analysis	0.931	Mean Difference (Final Values)	0.11	2-Sided	95	-2.40	2.62	No	Superiority or Other
OG000 OG001	Change from base study baseline in NPI score at week 52.	Mixed Models Analysis	0.524	Mean Difference (Final Values)	-0.80	2-Sided	95	-3.26	1.67	No	Superiority or Other
OG000 OG001	Change from base study baseline in NPI score at week 78.	Mixed Models Analysis	0.353	Mean Difference (Final Values)	-2.03	2-Sided	95	-6.32	2.27	No	Superiority or Other

Title

Denominators

Categories

Week 26 (N = 176, 240)

Title	Measurements
	OG0002.17± 0.86 OG0011.47± 0.73

Week 52 (N = 110, 163)

Title	Measurements
	OG0003.82± 0.95 OG0011.98± 0.79

Week 78 (N = 51, 81)

Title	Measurements
	OG0006.60± 1.69 OG0013.29± 1.35

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	Change from extension study baseline in NPI score at week 26.	Mixed Models Analysis	0.531	Mean Difference (Final Values)	-0.71	2-Sided	95	-2.92	1.51	No	Superiority or Other
OG000 OG001	Change from extension study baseline in NPI score at week 52.	Mixed Models Analysis	0.137	Mean Difference (Final Values)	-1.84	2-Sided	95	-4.28	0.59	No	Superiority or Other
OG000 OG001	Change from extension study baseline in NPI score at week 78.	Mixed Models Analysis	0.128	Mean Difference (Final Values)	-3.32	2-Sided	95	-7.60	0.96	No	Superiority or Other

Title

Denominators

Categories

Week 6 (N= 197, 255)

Title	Measurements
	OG000-2.61± 0.22 OG001-2.55± 0.19

Week 19 (N = 184, 241)

Title	Measurements
	OG000-3.13± 0.22 OG001-3.01± 0.19

Week 32 (N = 141, 204)

Title	Measurements
	OG000-3.75± 0.24 OG001-3.65± 0.20

Week 45 (N = 117, 171)

Title	Measurements
	OG000-4.44± 0.26 OG001-4.26± 0.21

Week 78 (N = 65, 94)

Title	Measurements
	OG000-5.50± 0.32 OG001-5.54± 0.26

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	Change from base study baseline in MMSE score at Week 6.	Mixed Models Analysis	0.811	Mean Difference (Final Values)	0.07	2-Sided	95	-0.49	0.63	No	Superiority or Other
OG000 OG001	Change from base study baseline in MMSE score at Week 19.	Mixed Models Analysis	0.681	Mean Difference (Final Values)	0.12	2-Sided	95	-0.45	0.69	No	Superiority or Other
OG000 OG001	Change from extension study baseline in MMSE score at Week 32.	Mixed Models Analysis	0.742	Mean Difference (Final Values)	0.10	2-Sided	95	-0.51	0.72	No	Superiority or Other
OG000 OG001	Change from extension study baseline in MMSE score at Week 45.	Mixed Models Analysis	0.598	Mean Difference (Final Values)	0.18	2-Sided	95	-0.48	0.83	No	Superiority or Other
OG000 OG001	Change from extension study baseline in MMSE score at Week 78.	Mixed Models Analysis	0.922	Mean Difference (Final Values)	-0.04	2-Sided	95	-0.85	0.77	No	Superiority or Other

Title

Denominators

Categories

Week 6 (N = 195, 255)

Title	Measurements
	OG000-0.67± 0.19 OG001-0.26± 0.16

Week 19 (N = 182, 241)

Title	Measurements
	OG000-1.16± 0.21 OG001-0.69± 0.18

Week 32 (N = 140, 204)

Title	Measurements
	OG000-1.85± 0.24 OG001-1.40± 0.20

Week 45 (N = 116, 171)

Title	Measurements
	OG000-2.57± 0.28 OG001-2.05± 0.24

Week 78 (N = 64, 94)

Title	Measurements
	OG000-3.69± 0.39 OG001-3.42± 0.32

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	Change from extension study baseline in MMSE score at Week 6.	Mixed Models Analysis	0.099	Mean Difference (Final Values)	0.41	2-Sided	95	-0.08	0.90	No	Superiority or Other
OG000 OG001	Change from extension study baseline in MMSE score at Week 19.	Mixed Models Analysis	0.089	Mean Difference (Final Values)	0.47	2-Sided	95	-0.07	1.01	No	Superiority or Other
OG000 OG001	Change from extension study baseline in MMSE score at Week 32.	Mixed Models Analysis	0.152	Mean Difference (Final Values)	0.45	2-Sided	95	-0.17	1.08	No	Superiority or Other
OG000 OG001	Change from extension study baseline in MMSE score at Week 45.	Mixed Models Analysis	0.160	Mean Difference (Final Values)	0.52	2-Sided	95	-0.21	1.25	No	Superiority or Other
OG000 OG001	Change from extension study baseline in MMSE score at Week 78.	Mixed Models Analysis	0.603	Mean Difference (Final Values)	0.26	2-Sided	95	-0.73	1.26	No	Superiority or Other