Trial Outcomes & Findings for Evaluating The Safety Of Donepezil Hydrochloride (Aricept) For Up To 1 Year In The Treatment Of The Cognitive Dysfunction Exhibited By Children With Down Syndrome - Follow-Up To A 10-Week, Double-Blind, Placebo-Controlled Trial (NCT NCT00675025)

Last Updated: 2021-03-29

Results Overview

VABS-II/PCRF assessed participant's adaptive behaviors on 3 domains (each has 3 sub-domains): Communication (receptive, expressive, written), Daily Living Skills (personal, domestic, community), Socialization (interpersonal relationships, play a leisure time, coping skills). Parent/caregiver rated participant's behavior for sub-domains from 0 (never present) to 2 (always present). Raw scores from sub-domains converted into standardized score(V-scale scores) ranged:1-24 for each sub-domain, mean=15,standard deviation(SD)=3,higher scores=higher level of adaptive functioning and were summed to obtain V-scale composite score ranged 9-216, mean=100,SD=15,higher scores=higher level of adaptive functioning, positive change=improvement in adaptive functioning. Composite and individual analyses, both raw and standardized scores, were not performed due to lack of significant differences between donepezil and placebo in parent study.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

117 participants

Primary outcome timeframe

Visit 1 (baseline); Early Termination Visit (Week 36)

Results posted on

2021-03-29

Participant Flow

This study was recruited at 24 centers in the United States during the period of 4 Apr 2008 to 15 Dec 2008. All participants who completed the double-blind (DB) placebo-controlled, 10 week study (Study 2020-A001-219 \[NCT00570128\]) were offered enrollment in this study.

The Screening and baseline activities for this study took place on the same day as the Week 10 final visit of the double-blind (DB) study (2020-A001-219 \[NCT00570128\]).

Participant milestones

Participant milestones
Measure	Prior Donepezil-DB Participants who received donepezil in the double-blind study E2020-A001-219 (NCT00570128) were continued in this open label extension (OLE) study to be treated with donepezil titrated to achieve a final dose of 0.1 - 0.2 milligram per kilogram per day (mg/kg/day) using liquid formulated at 5 mg/5 milliliter (mL) for up to approximately Week 42.	Prior Placebo-DB Participants who received matched placebo in the double-blind study E2020-A001-219 (NCT00570128) were continued in this OLE study to be treated with donepezil titrated to achieve a final dose of 0.1 - 0.2 mg/kg/day using liquid formulated at 5 mg/5 mL for up to approximately Week 42.
Overall Study STARTED	54	63
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	54	63

Reasons for withdrawal

Reasons for withdrawal
Measure	Prior Donepezil-DB Participants who received donepezil in the double-blind study E2020-A001-219 (NCT00570128) were continued in this open label extension (OLE) study to be treated with donepezil titrated to achieve a final dose of 0.1 - 0.2 milligram per kilogram per day (mg/kg/day) using liquid formulated at 5 mg/5 milliliter (mL) for up to approximately Week 42.	Prior Placebo-DB Participants who received matched placebo in the double-blind study E2020-A001-219 (NCT00570128) were continued in this OLE study to be treated with donepezil titrated to achieve a final dose of 0.1 - 0.2 mg/kg/day using liquid formulated at 5 mg/5 mL for up to approximately Week 42.
Overall Study Study Terminated by Sponsor	38	42
Overall Study Adverse Event	6	11
Overall Study Lost to Follow-up	6	4
Overall Study Withdrawal by Subject	4	6

Baseline Characteristics

Evaluating The Safety Of Donepezil Hydrochloride (Aricept) For Up To 1 Year In The Treatment Of The Cognitive Dysfunction Exhibited By Children With Down Syndrome - Follow-Up To A 10-Week, Double-Blind, Placebo-Controlled Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Prior Donepezil-DB n=54 Participants Participants who received donepezil in the double-blind study E2020-A001-219 (NCT00570128) were continued in this OLE study to be treated with donepezil titrated to achieve a final dose of 0.1 - 0.2 mg/kg/day using liquid formulated at 5 mg/5 mL for up to approximately Week 42.	Prior Placebo-DB n=63 Participants Participants who received matched placebo in the double-blind study E2020-A001-219 (NCT00570128) were continued in this OLE study to be treated with donepezil titrated to achieve a final dose of 0.1 - 0.2 mg/kg/day using liquid formulated at 5 mg/5 mL for up to approximately Week 42.	Total n=117 Participants Total of all reporting groups
Age, Continuous	13.4 years STANDARD_DEVIATION 2.4 • n=93 Participants	13.2 years STANDARD_DEVIATION 2.2 • n=4 Participants	13.2 years STANDARD_DEVIATION 3.3 • n=27 Participants
Sex: Female, Male Female	23 Participants n=93 Participants	34 Participants n=4 Participants	57 Participants n=27 Participants
Sex: Female, Male Male	31 Participants n=93 Participants	29 Participants n=4 Participants	60 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	4 Participants n=4 Participants	4 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	2 Participants n=93 Participants	3 Participants n=4 Participants	5 Participants n=27 Participants
Race (NIH/OMB) White	46 Participants n=93 Participants	55 Participants n=4 Participants	101 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=93 Participants	1 Participants n=4 Participants	7 Participants n=27 Participants

PRIMARY outcome

Timeframe: Visit 1 (baseline); Early Termination Visit (Week 36)

Population: Analyses were performed on the Intent-to-treat population. The VABS-II/PCRF composite score, individual analyses of each of the 3 domains and the 9 sub-domains by both raw and standardized scores were not performed due to a lack of significant differences between donepezil and placebo subgroups; the data are provided as listings.

Outcome measures

Outcome measures
Measure	Prior Donepezil-DB n=44 Participants Participants who received donepezil in the double-blind study E2020-A001-219 (NCT00570128) were continued in this OLE study to be treated with donepezil titrated to achieve a final dose of 0.1 - 0.2 mg/kg/day using liquid formulated at 5 mg/5 mL for up to approximately Week 42.	Prior Placebo-DB n=45 Participants Participants who received matched placebo in the double-blind study E2020-A001-219 (NCT00570128) were continued in this OLE study to be treated with donepezil titrated to achieve a final dose of 0.1 - 0.2 mg/kg/day using liquid formulated at 5 mg/5 mL for up to approximately Week 42.
Change From Visit 1 (Baseline) to Visit 4 or Early Termination in the Vineland Adaptive Behavior Scales, 2nd Edition, Parent/Caregiver Rating Form (VABS-II/PCRF) Sum of the 9 Sub-domain V-scores Baseline (Week 10 of DB study)	87.73 units on a scale Standard Deviation 16.58	92.02 units on a scale Standard Deviation 17.51
Change From Visit 1 (Baseline) to Visit 4 or Early Termination in the Vineland Adaptive Behavior Scales, 2nd Edition, Parent/Caregiver Rating Form (VABS-II/PCRF) Sum of the 9 Sub-domain V-scores Early termination visit	89.37 units on a scale Standard Deviation 20.9	91.25 units on a scale Standard Deviation 18.45

Adverse Events

Prior Donepezil-DB

Serious events: 0 serious events

Other events: 37 other events

Deaths: 0 deaths

Prior Placebo-DB

Serious events: 0 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Eisai Medical Services

Eisai Inc

Phone: 1-888-422-4743

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Prior Donepezil-DB n=54 participants at risk Participants who received donepezil in the double-blind study E2020-A001-219 (NCT00570128) were continued in this OLE study to be treated with donepezil titrated to achieve a final dose of 0.1 - 0.2 mg/kg/day using liquid formulated at 5 mg/5 mL for up to approximately Week 42.	Prior Placebo-DB n=63 participants at risk Participants who received matched placebo in the double-blind study E2020-A001-219 (NCT00570128) were continued in this OLE study to be treated with donepezil titrated to achieve a final dose of 0.1 - 0.2 mg/kg/day using liquid formulated at 5 mg/5 mL up to approximately Week 42.
Ear and labyrinth disorders Ear pain	3.7% 2/54 • Baseline up to early termination visit (Week 36)	1.6% 1/63 • Baseline up to early termination visit (Week 36)
Gastrointestinal disorders Abdominal pain, upper	9.3% 5/54 • Baseline up to early termination visit (Week 36)	6.3% 4/63 • Baseline up to early termination visit (Week 36)
Gastrointestinal disorders Diarrhea	14.8% 8/54 • Baseline up to early termination visit (Week 36)	23.8% 15/63 • Baseline up to early termination visit (Week 36)
Gastrointestinal disorders Flatulence	0.00% 0/54 • Baseline up to early termination visit (Week 36)	3.2% 2/63 • Baseline up to early termination visit (Week 36)
Gastrointestinal disorders Frequent bowel movements	0.00% 0/54 • Baseline up to early termination visit (Week 36)	3.2% 2/63 • Baseline up to early termination visit (Week 36)
Gastrointestinal disorders Nausea	3.7% 2/54 • Baseline up to early termination visit (Week 36)	6.3% 4/63 • Baseline up to early termination visit (Week 36)
Gastrointestinal disorders Vomiting	7.4% 4/54 • Baseline up to early termination visit (Week 36)	6.3% 4/63 • Baseline up to early termination visit (Week 36)
General disorders Fatigue	1.9% 1/54 • Baseline up to early termination visit (Week 36)	4.8% 3/63 • Baseline up to early termination visit (Week 36)
General disorders Pyrexia	1.9% 1/54 • Baseline up to early termination visit (Week 36)	4.8% 3/63 • Baseline up to early termination visit (Week 36)
Infections and infestations Ear infection	1.9% 1/54 • Baseline up to early termination visit (Week 36)	3.2% 2/63 • Baseline up to early termination visit (Week 36)
Infections and infestations Gastroenteritis viral	0.00% 0/54 • Baseline up to early termination visit (Week 36)	3.2% 2/63 • Baseline up to early termination visit (Week 36)
Infections and infestations Nasopharyngitis	3.7% 2/54 • Baseline up to early termination visit (Week 36)	0.00% 0/63 • Baseline up to early termination visit (Week 36)
Infections and infestations Pharyngitis, streptococcal	3.7% 2/54 • Baseline up to early termination visit (Week 36)	0.00% 0/63 • Baseline up to early termination visit (Week 36)
Infections and infestations Sinusitis	11.1% 6/54 • Baseline up to early termination visit (Week 36)	12.7% 8/63 • Baseline up to early termination visit (Week 36)
Infections and infestations Upper respiratory tract infection	3.7% 2/54 • Baseline up to early termination visit (Week 36)	11.1% 7/63 • Baseline up to early termination visit (Week 36)
Nervous system disorders Headache	1.9% 1/54 • Baseline up to early termination visit (Week 36)	6.3% 4/63 • Baseline up to early termination visit (Week 36)
Nervous system disorders Somnolence	7.4% 4/54 • Baseline up to early termination visit (Week 36)	1.6% 1/63 • Baseline up to early termination visit (Week 36)
Psychiatric disorders Abnormal behavior	1.9% 1/54 • Baseline up to early termination visit (Week 36)	4.8% 3/63 • Baseline up to early termination visit (Week 36)
Psychiatric disorders Aggression	0.00% 0/54 • Baseline up to early termination visit (Week 36)	3.2% 2/63 • Baseline up to early termination visit (Week 36)
Psychiatric disorders Initial insomnia	3.7% 2/54 • Baseline up to early termination visit (Week 36)	0.00% 0/63 • Baseline up to early termination visit (Week 36)
Psychiatric disorders Irritability	5.6% 3/54 • Baseline up to early termination visit (Week 36)	1.6% 1/63 • Baseline up to early termination visit (Week 36)
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/54 • Baseline up to early termination visit (Week 36)	6.3% 4/63 • Baseline up to early termination visit (Week 36)
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/54 • Baseline up to early termination visit (Week 36)	6.3% 4/63 • Baseline up to early termination visit (Week 36)
Respiratory, thoracic and mediastinal disorders Oroparyngeal pain	0.00% 0/54 • Baseline up to early termination visit (Week 36)	3.2% 2/63 • Baseline up to early termination visit (Week 36)
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	5.6% 3/54 • Baseline up to early termination visit (Week 36)	1.6% 1/63 • Baseline up to early termination visit (Week 36)
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/54 • Baseline up to early termination visit (Week 36)	3.2% 2/63 • Baseline up to early termination visit (Week 36)
Skin and subcutaneous tissue disorders Furuncle	3.7% 2/54 • Baseline up to early termination visit (Week 36)	1.6% 1/63 • Baseline up to early termination visit (Week 36)
Skin and subcutaneous tissue disorders Rash	0.00% 0/54 • Baseline up to early termination visit (Week 36)	3.2% 2/63 • Baseline up to early termination visit (Week 36)