Efficacy and Safety of Donepezil Hydrochloride in Preadol... | NCT00688376

ID	Type	Description	Link
E2020-G000-334	Registry Identifier	NCT00687635
2007-005435-28	EudraCT Number

Name	Class
Eisai Limited	INDUSTRY

Label	Type	Description	Intervention Names
1	Experimental		Drug: Donepezil hydrochloride
2	Placebo Comparator		Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Donepezil hydrochloride	Drug	During the 12-week Double-Blind Phase, subjects will receive oral donepezil hydrochloride tablets starting at a dose of 3 mg once daily. Doses will be increased incrementally at successive 3-week intervals on the basis of weight and tolerability. The final daily dose will be 3, 5, or 10 mg depending on body weight. During the Blinded Extension Phase, all subjects will receive active treatment (donepezil).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in the Test of Variables in Attention-Continuous Performance Test (TOVA-CPT) "D-prime" Standard Score (SS) at Week 12	TOVA-CPT test has a standardized computer game-like format that tests attention and simple impulse control. It precisely measures a person's reaction time to clicking on correct targets versus incorrect targets. Scores are based on the number of "Hits" (correct responses), omission errors (failure to respond), commission errors/"False Alarms" (incorrect responses), response time, and sensitivity ("d-prime"). "D-prime" a dimensionless statistics is a measure of distractibility and reflects how well a person reacts correctly versus incorrectly. A higher value of "d-prime" is reached by having more "Hits" (correct response) and fewer "False Alarms" (incorrect response). Analysis was based on three factors: the "d-prime" standard score, reaction time variability standard score, and response time standard score. Standard scores less than or equal to 80 were significant for an attention deficit disorder. Standard scores greater than 80 were not significant for an attention deficit disorder.	Baseline and Week 12

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in the TOVA-CPT "D-prime" Standard Score (SS) at Week 6	TOVA-CPT test has a standardized computer game-like format that tests attention and simple impulse control. It precisely measures a person's reaction time to clicking on correct targets versus incorrect targets. Scores are based on the number of "Hits" (correct responses), omission errors (failure to respond), commission errors/"False Alarms" (incorrect responses), response time, and sensitivity ("d-prime"). "D-prime" a dimensionless statistics is a measure of distractibility and reflects how well a person reacts correctly versus incorrectly. A higher value of "d-prime" is reached by having more "Hits" (correct response) and fewer "False Alarms" (incorrect response). Analysis was based on three factors: the "d-prime" standard score, reaction time variability standard score, and response time standard score. Standard scores less than or equal to 80 were significant for an attention deficit disorder. Standard scores greater than 80 were not significant for an attention deficit disorder.

Eligibility Module

Eligibility Criteria

The subject must have received at least one cycle of chemotherapy and/or cranial radiation, and must have completed this treatment at least one year before screening takes place for entry into this study.
Subjects may be male or female; age range: 6 - 17.5 years; weight ≥ 20 kg. They must be physically healthy and able to move about, with or without aids, must be living in the community, and must have adequate motor skills as shown by tests that will be given at the time of screening. The subject's eyesight and hearing must be good enough to allow cooperation with tests and physical examinations. Additionally, they must be able to swallow tablets.
There must be subjective complaints by subject and/or parent of difficulties in school or other daily activities, possibly related to impairments in attention. These difficulties must have emerged after treatment for cancer and must still be present 12 months after cessation of treatment. There must also be objective evidence for this impairment, as shown by a test that will be given to the subject at the time of screening.
The IQ must be >70 according to tests that will be given at the time of screening.
The first language in which the subject learned to read and write must be one that uses Roman lettering (a, b, c, etc.) and Arabic numerals (1, 2, 3, etc.).
The subject must not have previously taken any drugs in the class known as cholinesterase inhibitors.
A parent or legal guardian must be available who is willing and able to complete all of the outcome measures, to administer medications, and to accompany the subject to the required clinic visits.
Subjects with diabetes or thyroid disease may still be eligible if certain medical requirements are satisfied.
Female subjects who could become pregnant must undergo pregnancy testing and must agree to use contraception.

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from the study:

Inability to perform the required tests (for example, because of aphasia, motor deficits affecting the dominant hand, or mental retardation).
Motor coordination not sufficient, according to tests to be conducted at the time of screening.
Recurrence of cancer. If this happens, the subject will have to withdraw from the study.
Mental retardation/developmental disability.
Certain medications, such as methylphenidate, are not allowed during the study.
Major depression.
Problems with the digestive tract that could affect the subject's ability to absorb the study drug.
Hypersensitivity to a chemical class known as piperidine derivatives.
Certain other medical conditions as determined by clinical staff.
Alcoholism, drug abuse, or organic brain disease other than that caused by the cancer or its treatment.
Pregnancy, nursing, or unwillingness to undergo pregnancy testing if requested by clinical staff.
Pregnancy, lactation or plans to become pregnant, or unwilling to take a screening Beta-human chorionic gonadotropin (ßhCG) test if a female >10 years of age.
If sexually active, unwillingness to use birth control (males and females).
Plans for certain types of elective surgery that would occur while the study is in progress.
Plans for travel or other events that would interfere with the study schedule.
Active treatment with another investigational drug within 3 months of the screening visit.

Facility	Status	City	State	ZIP	Country	Contacts
		Stanford	California	94305-5826	United States

ID	Title	Description
FG000	Donepezil	Donepezil 3 mg, 5 mg, or 10 mg donepezil Immediate Release (IR) orally, once daily
FG001	Placebo	Placebo, matching 3 mg, 5 mg, and 10 mg placebo tablets administered orally, once daily

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 Test of Variables in Attention-Continuous Performance Test (TOVA-CPT) "D-prime" Standard Score (SS) at Week 12

TOVA-CPT test has a standardized computer game-like format that tests attention and simple impulse control. It precisely measures a person's reaction time to clicking on correct targets versus incorrect targets. Scores are based on the number of "Hits" (correct responses), omission errors (failure to respond), commission errors/"False Alarms" (incorrect responses), response time, and sensitivity ("d-prime"). "D-prime" a dimensionless statistics is a measure of distractibility and reflects how well a person reacts correctly versus incorrectly. A higher value of "d-prime" is reached by having more "Hits" (correct response) and fewer "False Alarms" (incorrect response). Analysis was based on three factors: the "d-prime" standard score, reaction time variability standard score, and response time standard score. Standard scores less than or equal to 80 were significant for an attention deficit disorder. Standard scores greater than 80 were not significant for an attention deficit disorder.

Intent-to-Treat (ITT) Last Observed Carried Forward (LOCF) population included all safety participants for whom the TOVA-CPT "d-prime" standard score was available at both Screening and at least one "d-prime" score from the treatment period, in addition to having a post-Baseline safety assessment.

Posted

Mean

Standard Deviation

d-prime

Baseline and Week 12

ID	Title	Description
OG000	Donepezil	Donepezil 3 mg, 5 mg, or 10 mg donepezil Immediate Release (IR) orally, once daily
OG001	Placebo	Placebo, matching 3 mg, 5 mg, and 10 mg placebo tablets administered orally, once daily

Units	Counts
Participants	OG00039 OG00130

Title

Denominators

Categories

Title	Measurements
	OG0005.2± 8.77 OG0014.5± 7.39

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	P-values, least squares (LS) mean, and 95% confidence interval (CI) were obtained from Analysis of Covariance (ANCOVA) model with treatment group as a factor and Baseline value as covariate.	ANCOVA		0.694		LS mean difference	0.8			2-Sided	95	-3.22	4.8					Superiority or Other (legacy)

Secondary

Change From Baseline in the TOVA-CPT "D-prime" Standard Score (SS) at Week 6

Intent-to-Treat (ITT) Last Observed Carried Forward (LOCF) population included all safety participants for whom the TOVA-CPT d-prime standard score was available at both Screening and at least one visit after the first dose of study drug during the Double-Blind Phase.

Posted

Mean

Standard Deviation

d-prime

Baseline and Week 6

ID	Title	Description
OG000	Donepezil	Donepezil 3 mg, 5 mg, or 10 mg donepezil Immediate Release (IR) orally, once daily
OG001	Placebo

Secondary

Change From Baseline in the Reaction Time Variability Standard Score (RTVSS) and Response Time Standard Score (RTSS) at Weeks 6 and 12

The Reaction Time Variability is defined as the time measurement of how consistently the switch is pressed. The Response Time is the measurement of how fast or slow information is processed and responded to by the participant. The testing process was as described in a previous outcome measure. Standard scores less than or equal to 80 were significant for an attention deficit disorder. Standard scores greater than 80 were not significant for an attention deficit disorder.

Posted

Mean

Standard Deviation

milliseconds

Baseline, Weeks 6 and 12

ID	Title	Description
OG000	Donepezil	Donepezil 3 mg, 5 mg, or 10 mg donepezil Immediate Release (IR) orally, once daily
OG001	Placebo	Placebo, matching 3 mg, 5 mg, and 10 mg placebo tablets administered orally, once daily

Units	Counts

Secondary

Change From Baseline in the Global Executive Composite Score, Behavioral Regulation Index, Metacognition Index, and Working Memory Subscale

Behavioral Rating Inventory of Executive Functioning test evaluates impairment of executive function(planning and organization),memory,and sustained attention in children aged 5-18 years with wide range of developmental and acquired neurological conditions.Survey assess parent/guardian's perception of their child's executive functioning in home and school environments,which relate to daily function(as judged by parent).Each survey contains 86 items scored as;1(behavior is never a problem),2(behavior is sometimes a problem),or 3(behavior is often a problem).Data was presented as t-scores(raw scale scores are used to generate t-scores)for Global Executive Composite Score(t-score range 72-216),Behavioral Regulation Index(t-score range 28-84;inhibit,shift,and emotional control),Metacognition Inde (t-score range 44-132;initiate,working memory,plan/organize,organization of materials, and monitor),and Working Memory Subscale(t-score range 35-90).Higher scores indicate decline in performance.

ITT population LOCF

Posted

Mean

Standard Deviation

t-scores

Baseline and Week 12

ID	Title	Description
OG000	Donepezil	Donepezil 3 mg, 5 mg, or 10 mg donepezil Immediate Release (IR) orally, once daily
OG001	Placebo	Placebo, matching 3 mg, 5 mg, and 10 mg placebo tablets administered orally, once daily

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG0030 affected25 at risk
Eosinophilia	Blood and lymphatic system disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Palpitations	Cardiac disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Hydrocele	Congenital, familial and genetic disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0021 affected34 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Vertigo positional	Ear and labyrinth disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Precocious puberty	Endocrine disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Eye discharge	Eye disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Photophobia	Eye disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Tear discoloration	Eye disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Vision blurred	Eye disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0003 affected40 at risk EG0013 affected31 at risk EG0021 affected34 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0002 affected40 at risk EG0012 affected31 at risk EG0022 affected34 at risk EG003
Bowel movement irregularity	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0021 affected34 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0003 affected40 at risk EG0011 affected31 at risk EG0022 affected34 at risk EG003
Frequent bowel movements	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0007 affected40 at risk EG0012 affected31 at risk EG0021 affected34 at risk EG003
Stomach discomfort	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0012 affected31 at risk EG0020 affected34 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (11.0)	Systematic Assessment	EG0002 affected40 at risk EG0011 affected31 at risk EG0022 affected34 at risk EG003
Asthenia	General disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0012 affected31 at risk EG0021 affected34 at risk EG003
Chills	General disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0021 affected34 at risk EG003
Fatigue	General disorders	MedDRA (11.0)	Systematic Assessment	EG0002 affected40 at risk EG0013 affected31 at risk EG0022 affected34 at risk EG003
Pyrexia	General disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0012 affected31 at risk EG0020 affected34 at risk EG003
Xerosis	General disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Bronchitis	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Cellulitis	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Ear infection	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0021 affected34 at risk EG003
Furuncle	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Influenza	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0004 affected40 at risk EG0013 affected31 at risk EG0022 affected34 at risk EG003
Otitis media	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Pharyngitis	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Pharyngitis streptococcal	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Rhinitis	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0011 affected31 at risk EG0022 affected34 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Limb injury	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Urine analysis abnormal	Investigations	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Weight increased	Investigations	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Anorexia	Metabolism and nutrition disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Coccydynia	Musculoskeletal and connective tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Kyphosis	Musculoskeletal and connective tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0004 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0002 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Ataxia	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Burning sensation	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Cerebellar syndrome	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Dizziness	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Dizziness exertional	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Headache	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG00010 affected40 at risk EG0017 affected31 at risk EG0022 affected34 at risk EG003
Hyperreflexia	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Hypersomnia	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Memory impairment	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0002 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Nervous system disorder	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Poor quality sleep	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Sinus headache	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Somnolence	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Syncope	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Tremor	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Abnormal behavior	Psychiatric disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Affect lability	Psychiatric disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Aggression	Psychiatric disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Anxiety	Nervous system disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Attention deficit/Hyperactivity disorder	Psychiatric disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Depressed mood	Psychiatric disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Mood swings	Psychiatric disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Nightmare	Psychiatric disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Tearfulness	Psychiatric disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Micturition urgency	Renal and urinary disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Amenorrhoea	Reproductive system and breast disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0021 affected34 at risk EG003
Menstruation delayed	Reproductive system and breast disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0004 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Pharyngeal erythema	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0021 affected34 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Sneezing	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0003 affected40 at risk EG0012 affected31 at risk EG0020 affected34 at risk EG003
Rash papular	Skin and subcutaneous tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Flushing	Vascular disorders	MedDRA (11.0)	Systematic Assessment	EG0000 affected40 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Pallor	Vascular disorders	MedDRA (11.0)	Systematic Assessment	EG0001 affected40 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003

ID	Term
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D007189	Indans
D007192	Indenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D010880	Piperidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011083	Polycyclic Compounds

ID	Title	Description
BG000	Donepezil	Donepezil 3 mg, 5 mg, or 10 mg donepezil Immediate Release (IR) orally, once daily
BG001	Placebo	Placebo, matching 3 mg, 5 mg, and 10 mg placebo tablets administered orally, once daily
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Donepezil Double-Blind Phase	Donepezil 3 mg, 5 mg, or 10 mg donepezil Immediate Release (IR) orally, once daily	40	1	40	30	40
EG001	Placebo Double-Blind Phase	Placebo, matching 3 mg, 5 mg, and 10 mg placebo tablets administered orally, once daily	31	1	31	20	31
EG002	Donepezil Blinded Extension Phase	Donepezil 3 mg, 5 mg, or 10 mg donepezil Immediate Release (IR) orally, once daily	34	0	34	21	34
EG003	Placebo Blinded Extension Phase	Placebo, matching 3 mg, 5 mg, and 10 mg placebo tablets administered orally, once daily	25	0	25	15	25