Down Syndrome
Conditions
Brief summary
The purpose of this study is to determine the safety of donepezil hydrochloride (Aricept) in children with Down syndrome who have finished the preceding 10-week, double-blind study of donepezil hydrochloride. Medical tests for drug safety will be conducted at each clinic visit.
Detailed description
All children in this study will take donepezil hydrochloride once a day, and will come back to the clinic at 8, 24 and 42 weeks after the study has begun. In between these clinic visits, the clinical staff will telephone the child's parent or caregiver to discuss drug safety observations and possible changes in drug dose. At the end of the study (42 weeks), psychological testing will also be given to determine how well the child is functioning.
Interventions
Liquid form Aricept - 5 mg/5 mL donepezil hydrochloride.
Sponsors
Pfizer
Eisai Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Down syndrome (established during study E2020-A001-220). * Completion of study E2020-A001-219 (NCT00570128 \[also known as A2501059\]) with no ongoing seroius adverse events and no severe drug reactions.
Exclusion criteria
* Weight less than 20 kg. * Clinically significant conditions affecting absorption, distribution or metabolism of the study medication. * No reliable parent or caregiver, or unwillingness or inability of parent or caregiver to fulfill the requirements of the study. * Females of childbearing potential who are not practicing an effective means of birth control.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Visit 1 (baseline); Early Termination Visit (Week 36) | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
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 \[NCT00570128\]).
Participants by arm
| Arm | Count |
|---|---|
| Prior Donepezil-DB 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. | 54 |
| 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. | 63 |
| Total | 117 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 11 |
| Overall Study | Lost to Follow-up | 6 | 4 |
| Overall Study | Study Terminated by Sponsor | 38 | 42 |
| Overall Study | Withdrawal by Subject | 4 | 6 |
Baseline characteristics
| Characteristic | Prior Placebo-DB | Total | Prior Donepezil-DB |
|---|---|---|---|
| Age, Continuous | 13.2 years STANDARD_DEVIATION 2.2 | 13.2 years STANDARD_DEVIATION 3.3 | 13.4 years STANDARD_DEVIATION 2.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 7 Participants | 6 Participants |
| Race (NIH/OMB) White | 55 Participants | 101 Participants | 46 Participants |
| Sex: Female, Male Female | 34 Participants | 57 Participants | 23 Participants |
| Sex: Female, Male Male | 29 Participants | 60 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 54 | 0 / 63 |
| other Total, other adverse events | 37 / 54 | 48 / 63 |
| serious Total, serious adverse events | 0 / 54 | 0 / 63 |
Outcome results
Primary
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
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Donepezil-DB | 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 |
| Prior Donepezil-DB | 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 |
| Prior Placebo-DB | 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) | 92.02 units on a scale | Standard Deviation 17.51 |
| Prior Placebo-DB | 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 | 91.25 units on a scale | Standard Deviation 18.45 |