Evaluating The Efficacy And Safety Of Donepezil Hydrochlo... | NCT00570128

ID	Type	Description	Link
A2501059	Other Identifier	Pfizer

Name	Class
Pfizer	INDUSTRY

Label	Type	Description	Intervention Names
Donepezil HCl	Active Comparator		Drug: Donepezil HCl
Placebo	Placebo Comparator		Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Donepezil HCl	Drug	Blinded donepezil 2.5 milligram per day (mg/day) (2.5 milliliter per day [mL/day]) orally for participants with body weight (BW) 20 and less than (<) 25 kilogram (kg), 5 mg/day (5 mL/day) orally for participants with BW 25 to <50 kg, and 10 mg/day (10 mL/day) orally for participants with BW greater than or equal to (>=) 50 kg liquid formulation (1 milligram per 1 milliliter [1 mg/1 mL]) (titrated to 0.1 to 0.2 milligram per kilogram per day [mg/kg/day] based on BW).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Mean Change From Baseline in V-Scale Composite Score (Sum of 9 Sub-Domains) of Vineland Adaptive Behavior Scales Second Edition-Parent Caregiver Rating Form (VABS-II/PCRF) at Week 10-Last Observation Carried Forward (LOCF)	The VABS-II/PCRF instrument was used in this study to assess 3 domains (each with 3 sub-domains): communication (sub-domains: receptive, expressive, and writing), daily living skills (sub-domains: personal, domestic, community), and socialization (sub-domains: interpersonal relationships, play/leisure time, coping skills). Raw scores (2=always present, 1=sometimes present, 0=seldom or never present) rated by the parent/caregiver from each sub-domain were converted to standardized scores called V-scores, which are based on age and a national sample of normal children. Each sub-domain v-scale score ranged from 1 (weakness) to 24 (strength). V-scores for the 9 sub-domains were summed to obtain a composite V-score ranging from 9 to 216. Higher scores indicate a higher level of adaptive functioning. A positive change from baseline indicates an improvement in adaptive functioning. Composite V-scores have a mean (50th percentile) of 100 and a standard deviation (SD) of 15.	Baseline, Week 10

Secondary Outcomes

Measure	Description	Time Frame
Mean Change From Baseline in V-Scale Composite Score (Sum of 9 Sub-domains) of Vineland Adaptive Behavior Scales Second Edition-Parent Caregiver Rating Form (VABS-II/PCRF) at Week 4 and 10-Observed Cases (OC)	The VABS-II/PCRF instrument was used in this study to assess 3 domains (each with 3 sub-domains): communication (sub-domains: receptive, expressive, writing), daily living skills (sub-domains: personal, domestic, community), and socialization (sub-domains: interpersonal relationships, play/leisure time, coping skills). Raw scores (2=always present, 1=sometimes present, 0=seldom or never present) rated by the parent/caregiver from each sub-domain were converted to standardized scores called V-scores, which are based on age and a national sample of normal children. Each sub-domain v-scale score ranged from 1 (weakness) to 24 (strength). V-scores for the 9 sub-domains were summed to obtain a composite V-score ranging from 9 to 216. Higher scores indicate a higher level of adaptive functioning. A positive change from baseline indicates an improvement in adaptive functioning. Composite V-scores have a mean (50th percentile) of 100 and a SD of 15.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Ages 10 to 17 years old, weight more than or equal to 20 kg
Male and female
Vineland-II Adaptive Behavior Scales (VABS-II)/Parent/Caregiver Rating Form (PCRF) standard composite score greater than (>) 55
Diagnosis of DS (trisomy 21) documented by chromosomal analysis (karyotyping). If such documentation is not available at screening, karyotyping will be performed with the screening labs and must be documented prior to baseline visit.
Naïve to approved or unapproved cholinesterase inhibitors is preferred however, prior use of these medications is allowed, provided that the medication was discontinued at least 3 months prior to screening and that it was not discontinued for lack of tolerability or efficacy or for the sole purpose of enrolling the subject in the study.
Subjects residing in the community
Must be expected to complete all procedures scheduled during the Screening and Baseline visits including all efficacy and safety parameters.
Must speak English and be verbal and able to be understood most of the time and must not use other forms of communication, signs, symbol boards or devices to supplement his/her communication ability
Must have a parent or other reliable caregiver who agrees to accompany the subject to all clinic visits, provide information about the subject as required by the protocol, and ensure compliance with the medication schedule
a Parent or Caregiver must be a constant and reliable informant with sufficient contact with the subject to have detailed knowledge of the subject's adaptive behavior in order to be able to complete the VABS-II/PCRF accurately. The same individual should complete the form at every visit.
Should be in good general health with no medical conditions that are considered both clinically significant and unstable
Clinical laboratory values within normal limits or abnormalities considered not clinically significant by the investigator and sponsor
Stable Type I (insulin-dependent) or Type II diabetes are eligible provided they are monitored regularly prior to and during the study to ensure adequate glucose control (fasting blood glucose <140 milligram per deciliter (mg/dl) and glycosylated hemoglobin [hemoglobin A1c] <8 percent (%) at screening).
Thyroid disease also may be included in the study provided they are euthyroid and stable on treatment for at least 3 months prior to screening.
History of seizure disorder is allowed provided that subjects are on stable treatment for at least 3 months and have not had a seizure within the past 6 months.
Independent in ambulation or ambulatory aided (example, walker or cane, wheelchair), vision and hearing (eyeglasses and/or hearing aid permissible) sufficient for achieving VABS-II/PCRF composite standard scores >55 and for cooperating with examinations and the Test of Verbal Expression and Reasoning (TOVER).

Exclusion Criteria:

Ages <10 or >17 years
Active or clinically significant conditions affecting absorption, distribution or metabolism of the study medication (example, inflammatory bowel disease, gastric or duodenal ulcers or severe lactose intolerance)
Known hypersensitivity to piperidine derivatives or cholinesterase inhibitors
Currently receiving cholinesterase inhibitors or who have received them in the 3 months prior to screening or with prior use >3 months prior to screening who stopped for lack of efficacy or tolerability
No reliable parent or caregiver, or participants, or caregivers who are unwilling or unable to complete any of the outcome measures and fulfill the requirements of this study
Clinically significant obstructive pulmonary disease or asthma untreated or not controlled by treatment within 3 months prior to screening
Recent (less than or equal to 2 years) hematologic/oncologic disorders (mild anemia allowed)
Evidence of active, clinically significant, and unstable gastrointestinal, renal, hepatic, endocrine or cardiovascular system disease
Current Diagnostic and Statistical Manual IV Text Revision (DSM-IV-TR) diagnosis of Major Depressive Disorder (MDD) or any current primary psychiatric diagnosis other than DS (as per DSM-IV)
Any condition which would make the subject or the caregiver, in the opinion of the investigator, unsuitable for the study
Unsuitability which includes female subjects who have begun menstruation and are thus of child-bearing potential, who may be sexually active and who are not practicing an effective means of birth control.

Facility	Status	City	State	ZIP	Country	Contacts
Phoenix Children's Hospital		Phoenix	Arizona	85016	United States
Clinical Study Centers, L.L.C.

ID	Title	Description
FG000	Donepezil HCl	Blinded donepezil hydrochloride (HCl) 2.5 milligram per day (mg/day) (2.5 milliliter per day [mL/day]) orally for participants with body weight (BW) 20 and less than (<) 25 kilogram (kg), 5 mg/day (5 mL/day) orally for participants with BW 25 to <50 kg, and 10 mg/day (10 mL/day) orally for participants with BW greater than or equal to (>=) 50 kg liquid formulation (1 milligram per 1 milliliter [1 mg/1 mL]) (titrated to 0.1 to 0.2 milligram per kilogram per day [mg/kg/day] based on BW).

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

Mean Change From Baseline in V-Scale Composite Score (Sum of 9 Sub-Domains) of Vineland Adaptive Behavior Scales Second Edition-Parent Caregiver Rating Form (VABS-II/PCRF) at Week 10-Last Observation Carried Forward (LOCF)

The VABS-II/PCRF instrument was used in this study to assess 3 domains (each with 3 sub-domains): communication (sub-domains: receptive, expressive, and writing), daily living skills (sub-domains: personal, domestic, community), and socialization (sub-domains: interpersonal relationships, play/leisure time, coping skills). Raw scores (2=always present, 1=sometimes present, 0=seldom or never present) rated by the parent/caregiver from each sub-domain were converted to standardized scores called V-scores, which are based on age and a national sample of normal children. Each sub-domain v-scale score ranged from 1 (weakness) to 24 (strength). V-scores for the 9 sub-domains were summed to obtain a composite V-score ranging from 9 to 216. Higher scores indicate a higher level of adaptive functioning. A positive change from baseline indicates an improvement in adaptive functioning. Composite V-scores have a mean (50th percentile) of 100 and a standard deviation (SD) of 15.

ITT population: all randomized participants who received at least one dose of study drug and had at least one post-baseline assessment for at least one efficacy variable irrespective of compliance and protocol violations. Here "Overall number of participants analyzed, N" signifies participants who were evaluable for this outcome measure.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Week 10

ID	Title	Description
OG000	Donepezil HCl	Blinded donepezil HCl 2.5 mg/day (2.5 mL/day) orally for participants with BW 20 and <25 kg, 5 mg/day (5 mL/day) orally for participants with BW 25 to <50 kg, and 10 mg/day (10 mL/day) orally for participants with BW >=50 kg liquid formulation (1 mg/1 mL) (titrated to 0.1 to 0.2 mg/kg/day based on BW).
OG001	Placebo	Liquid formulation matched to active treatment for oral administration.

Units	Counts
Participants	OG00061 OG00165

Title

Denominators

Categories

Baseline

Title	Measurements
	OG00083.1± 15.5 OG00185.7± 15.8

Mean change from baseline at Week 10

Title	Measurements
	OG000

Secondary

Mean Change From Baseline in V-Scale Composite Score (Sum of 9 Sub-domains) of Vineland Adaptive Behavior Scales Second Edition-Parent Caregiver Rating Form (VABS-II/PCRF) at Week 4 and 10-Observed Cases (OC)

The VABS-II/PCRF instrument was used in this study to assess 3 domains (each with 3 sub-domains): communication (sub-domains: receptive, expressive, writing), daily living skills (sub-domains: personal, domestic, community), and socialization (sub-domains: interpersonal relationships, play/leisure time, coping skills). Raw scores (2=always present, 1=sometimes present, 0=seldom or never present) rated by the parent/caregiver from each sub-domain were converted to standardized scores called V-scores, which are based on age and a national sample of normal children. Each sub-domain v-scale score ranged from 1 (weakness) to 24 (strength). V-scores for the 9 sub-domains were summed to obtain a composite V-score ranging from 9 to 216. Higher scores indicate a higher level of adaptive functioning. A positive change from baseline indicates an improvement in adaptive functioning. Composite V-scores have a mean (50th percentile) of 100 and a SD of 15.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Week 4 and Week 10

ID	Title	Description
OG000	Donepezil HCl

Secondary

Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER) Total Score at Week 4 and 10-OC

The TOVER is a participant-performance-based measure of expressive language function and verbal reasoning in response to questions about a series of stylized pictures showing identifiable scenarios. The 64-item test was specifically designed to assess language function in children and adults with down syndrome (DS) across a broad range of functional ability. The test used 23 multi-colored pictures to stimulate verbal responses to questions. The test was short (completed in 15 minutes) and fast-paced (2 to 4 questions per picture). Total score ranging from 0 to 64, was derived from 64 questions, where higher score indicates better functional ability.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Week 4 and Week 10

ID	Title	Description
OG000	Donepezil HCl	Blinded donepezil HCl 2.5 mg/day (2.5 mL/day) orally for participants with BW 20 and <25 kg, 5 mg/day (5 mL/day) orally for participants with BW 25 to <50 kg, and 10 mg/day (10 mL/day) orally for participants with BW >=50 kg liquid formulation (1 mg/1 mL) (titrated to 0.1 to 0.2 mg/kg/day based on BW).

Secondary

Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER) Total Score at Week 10-LOCF

The TOVER is a participant-performance-based measure of expressive language function and verbal reasoning in response to questions about a series of stylized pictures showing identifiable scenarios. The 64-item test was specifically designed to assess language function in children and adults with DS across a broad range of functional ability. The test used 23 multi-colored pictures to stimulate verbal responses to questions. The test was short (completed in 15 minutes) and fast-paced (2 to 4 questions per picture). Total score ranging from 0 to 64, was derived from 64 questions, where higher score indicates better functional ability.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Week 10

ID	Title	Description
OG000	Donepezil HCl	Blinded donepezil HCl 2.5 mg/day (2.5 mL/day) orally for participants with BW 20 and <25 kg, 5 mg/day (5 mL/day) orally for participants with BW 25 to <50 kg, and 10 mg/day (10 mL/day) orally for participants with BW >=50 kg liquid formulation (1 mg/1 mL) (titrated to 0.1 to 0.2 mg/kg/day based on BW).
OG001	Placebo

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain, upper	Gastrointestinal disorders	MedDRA 11.0	Systematic Assessment	EG0002 affected64 at risk EG0011 affected65 at risk
Constipation	Gastrointestinal disorders	MedDRA 11.0	Systematic Assessment	EG0000 affected64 at risk EG0012 affected65 at risk
Diarrhea	Gastrointestinal disorders	MedDRA 11.0	Systematic Assessment	EG00011 affected64 at risk EG00110 affected65 at risk
Fecal incontinence	Gastrointestinal disorders	MedDRA 11.0	Systematic Assessment	EG0002 affected64 at risk EG0010 affected65 at risk
Nausea	Gastrointestinal disorders	MedDRA 11.0	Systematic Assessment	EG0005 affected64 at risk EG0012 affected65 at risk
Vomiting	Gastrointestinal disorders	MedDRA 11.0	Systematic Assessment	EG0008 affected64 at risk EG0012 affected65 at risk
Fatigue	General disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected64 at risk EG0012 affected65 at risk
Pyrexia	General disorders	MedDRA 11.0	Systematic Assessment	EG0002 affected64 at risk EG0012 affected65 at risk
Bronchitis	Infections and infestations	MedDRA 11.0	Systematic Assessment	EG0002 affected64 at risk EG0010 affected65 at risk
Ear infection	Infections and infestations	MedDRA 11.0	Systematic Assessment	EG0001 affected64 at risk EG0013 affected65 at risk
Gastroenteritis	Infections and infestations	MedDRA 11.0	Systematic Assessment	EG0000 affected64 at risk EG0012 affected65 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 11.0	Systematic Assessment	EG0002 affected64 at risk EG0011 affected65 at risk
Nasopharyngitis	Infections and infestations	MedDRA 11.0	Systematic Assessment	EG0000 affected64 at risk EG0014 affected65 at risk
Pharyngitis	Infections and infestations	MedDRA 11.0	Systematic Assessment	EG0003 affected64 at risk EG0011 affected65 at risk
Sinusitis	Infections and infestations	MedDRA 11.0	Systematic Assessment	EG0001 affected64 at risk EG0013 affected65 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 11.0	Systematic Assessment	EG0006 affected64 at risk EG0015 affected65 at risk
Viral infection	Infections and infestations	MedDRA 11.0	Systematic Assessment	EG0002 affected64 at risk EG0010 affected65 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected64 at risk EG0013 affected65 at risk
Headache	Nervous system disorders	MedDRA 11.0	Systematic Assessment	EG0005 affected64 at risk EG0012 affected65 at risk
Lethargy	Nervous system disorders	MedDRA 11.0	Systematic Assessment	EG0002 affected64 at risk EG0010 affected65 at risk
Somnolence	Nervous system disorders	MedDRA 11.0	Systematic Assessment	EG0002 affected64 at risk EG0010 affected65 at risk
Insomnia	Psychiatric disorders	MedDRA 11.0	Systematic Assessment	EG0000 affected64 at risk EG0012 affected65 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 11.0	Systematic Assessment	EG0004 affected64 at risk EG0011 affected65 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 11.0	Systematic Assessment	EG0001 affected64 at risk EG0012 affected65 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 11.0	Systematic Assessment	EG0002 affected64 at risk EG0010 affected65 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 11.0	Systematic Assessment	EG0003 affected64 at risk EG0012 affected65 at risk

ID	Term
D008607	Intellectual Disability
D019954	Neurobehavioral Manifestations
D009461	Neurologic Manifestations
D009422	Nervous System Diseases
D000015	Abnormalities, Multiple
D000013	Congenital Abnormalities
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D025063	Chromosome Disorders
D030342	Genetic Diseases, Inborn

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 HCl	Blinded donepezil HCl 2.5 mg/day (2.5 mL/day) orally for participants with BW 20 and <25 kg, 5 mg/day (5 mL/day) orally for participants with BW 25 to <50 kg, and 10 mg/day (10 mL/day) orally for participants with BW >=50 kg liquid formulation (1 mg/1 mL) (titrated to 0.1 to 0.2 mg/kg/day based on BW).
BG001	Placebo	Liquid formulation matched to active treatment for oral administration.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Donepezil HCl	Blinded donepezil HCl 2.5 mg/day (2.5 mL/day) orally for participants with BW 20 and <25 kg, 5 mg/day (5 mL/day) orally for participants with BW 25 to <50 kg, and 10 mg/day (10 mL/day) orally for participants with BW >=50 kg liquid formulation (1 mg/1 mL) (titrated to 0.1 to 0.2 mg/kg/day based on BW).	0	64	0	64	45	64
EG001	Placebo	Liquid formulation matched to active treatment for oral administration.	0	65	1	65	42	65