Trial Outcomes & Findings for Evaluating The Efficacy And Safety Of Donepezil Hydrochloride (HCl) (Aricept) In Treating Cognitive Dysfunction Exhibited By Children With Down Syndrome (NCT NCT00570128)
NCT ID: NCT00570128
Last Updated: 2021-04-19
Results Overview
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.
COMPLETED
PHASE2
129 participants
Baseline, Week 10
2021-04-19
Participant Flow
This study was conducted at 35 centers in the United States during the period of 16 November 2007 to 05 September 2008.
Participant milestones
| Measure |
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).
|
Placebo
Liquid formulation matched to active treatment for oral administration.
|
|---|---|---|
|
Overall Study
STARTED
|
64
|
65
|
|
Overall Study
Intent to Treat (ITT) Population
|
62
|
65
|
|
Overall Study
COMPLETED
|
60
|
65
|
|
Overall Study
NOT COMPLETED
|
4
|
0
|
Reasons for withdrawal
| Measure |
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).
|
Placebo
Liquid formulation matched to active treatment for oral administration.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
Baseline Characteristics
Evaluating The Efficacy And Safety Of Donepezil Hydrochloride (HCl) (Aricept) In Treating Cognitive Dysfunction Exhibited By Children With Down Syndrome
Baseline characteristics by cohort
| Measure |
Donepezil HCl
n=64 Participants
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).
|
Placebo
n=65 Participants
Liquid formulation matched to active treatment for oral administration.
|
Total
n=129 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
13.0 years
STANDARD_DEVIATION 2.3 • n=5 Participants
|
13.0 years
STANDARD_DEVIATION 2.1 • n=7 Participants
|
13.0 years
STANDARD_DEVIATION 2.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
63 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
36 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
66 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
54 Participants
n=5 Participants
|
57 Participants
n=7 Participants
|
111 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
6 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 10Population: 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.
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.
Outcome measures
| Measure |
Donepezil HCl
n=61 Participants
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).
|
Placebo
n=65 Participants
Liquid formulation matched to active treatment for oral administration.
|
|---|---|---|
|
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)
Baseline
|
83.1 score on a scale
Standard Deviation 15.5
|
85.7 score on a scale
Standard Deviation 15.8
|
|
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)
Mean change from baseline at Week 10
|
4.74 score on a scale
Standard Deviation 9.2
|
4.22 score on a scale
Standard Deviation 8.5
|
SECONDARY outcome
Timeframe: Baseline, Week 4 and Week 10Population: 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. Here "Number analyzed" signifies participants who were evaluable for this outcome measure at given time points.
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.
Outcome measures
| Measure |
Donepezil HCl
n=61 Participants
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).
|
Placebo
n=65 Participants
Liquid formulation matched to active treatment for oral administration.
|
|---|---|---|
|
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)
Baseline
|
83.1 score on a scale
Standard Deviation 15.5
|
85.7 score on a scale
Standard Deviation 15.8
|
|
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)
Mean change from baseline at Week 4
|
1.5 score on a scale
Standard Deviation 6.4
|
2.6 score on a scale
Standard Deviation 8.5
|
|
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)
Mean change from baseline at Week 10
|
5.1 score on a scale
Standard Deviation 9.6
|
4.2 score on a scale
Standard Deviation 8.6
|
SECONDARY outcome
Timeframe: Baseline, Week 4 and Week 10Population: 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. Here "Number analyzed" signifies participants who were evaluable for this outcome measure at given time points.
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.
Outcome measures
| Measure |
Donepezil HCl
n=62 Participants
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).
|
Placebo
n=64 Participants
Liquid formulation matched to active treatment for oral administration.
|
|---|---|---|
|
Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER) Total Score at Week 4 and 10-OC
Mean change from baseline at Week 4
|
1.2 score on a scale
Standard Deviation 6.4
|
0.9 score on a scale
Standard Deviation 8.5
|
|
Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER) Total Score at Week 4 and 10-OC
Mean change from baseline at Week 10
|
2.6 score on a scale
Standard Deviation 6.2
|
1.9 score on a scale
Standard Deviation 5.5
|
|
Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER) Total Score at Week 4 and 10-OC
Baseline
|
20.7 score on a scale
Standard Deviation 12.2
|
21.6 score on a scale
Standard Deviation 11.4
|
SECONDARY outcome
Timeframe: Baseline, Week 10Population: 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.
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.
Outcome measures
| Measure |
Donepezil HCl
n=62 Participants
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).
|
Placebo
n=64 Participants
Liquid formulation matched to active treatment for oral administration.
|
|---|---|---|
|
Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER) Total Score at Week 10-LOCF
Baseline
|
20.7 score on a scale
Standard Deviation 12.2
|
21.6 score on a scale
Standard Deviation 11.4
|
|
Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER) Total Score at Week 10-LOCF
Mean change from baseline at Week 10
|
2.4 score on a scale
Standard Deviation 6.0
|
2.1 score on a scale
Standard Deviation 5.5
|
Adverse Events
Donepezil HCl
Placebo
Serious adverse events
| Measure |
Donepezil HCl
n=64 participants at risk
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).
|
Placebo
n=65 participants at risk
Liquid formulation matched to active treatment for oral administration.
|
|---|---|---|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/64 • Baseline up to 10 months
|
1.5%
1/65 • Baseline up to 10 months
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/64 • Baseline up to 10 months
|
1.5%
1/65 • Baseline up to 10 months
|
Other adverse events
| Measure |
Donepezil HCl
n=64 participants at risk
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).
|
Placebo
n=65 participants at risk
Liquid formulation matched to active treatment for oral administration.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain, upper
|
3.1%
2/64 • Baseline up to 10 months
|
1.5%
1/65 • Baseline up to 10 months
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/64 • Baseline up to 10 months
|
3.1%
2/65 • Baseline up to 10 months
|
|
Gastrointestinal disorders
Diarrhea
|
17.2%
11/64 • Baseline up to 10 months
|
15.4%
10/65 • Baseline up to 10 months
|
|
Gastrointestinal disorders
Fecal incontinence
|
3.1%
2/64 • Baseline up to 10 months
|
0.00%
0/65 • Baseline up to 10 months
|
|
Gastrointestinal disorders
Nausea
|
7.8%
5/64 • Baseline up to 10 months
|
3.1%
2/65 • Baseline up to 10 months
|
|
Gastrointestinal disorders
Vomiting
|
12.5%
8/64 • Baseline up to 10 months
|
3.1%
2/65 • Baseline up to 10 months
|
|
General disorders
Fatigue
|
1.6%
1/64 • Baseline up to 10 months
|
3.1%
2/65 • Baseline up to 10 months
|
|
General disorders
Pyrexia
|
3.1%
2/64 • Baseline up to 10 months
|
3.1%
2/65 • Baseline up to 10 months
|
|
Infections and infestations
Bronchitis
|
3.1%
2/64 • Baseline up to 10 months
|
0.00%
0/65 • Baseline up to 10 months
|
|
Infections and infestations
Ear infection
|
1.6%
1/64 • Baseline up to 10 months
|
4.6%
3/65 • Baseline up to 10 months
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/64 • Baseline up to 10 months
|
3.1%
2/65 • Baseline up to 10 months
|
|
Infections and infestations
Gastroenteritis viral
|
3.1%
2/64 • Baseline up to 10 months
|
1.5%
1/65 • Baseline up to 10 months
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/64 • Baseline up to 10 months
|
6.2%
4/65 • Baseline up to 10 months
|
|
Infections and infestations
Pharyngitis
|
4.7%
3/64 • Baseline up to 10 months
|
1.5%
1/65 • Baseline up to 10 months
|
|
Infections and infestations
Sinusitis
|
1.6%
1/64 • Baseline up to 10 months
|
4.6%
3/65 • Baseline up to 10 months
|
|
Infections and infestations
Upper respiratory tract infection
|
9.4%
6/64 • Baseline up to 10 months
|
7.7%
5/65 • Baseline up to 10 months
|
|
Infections and infestations
Viral infection
|
3.1%
2/64 • Baseline up to 10 months
|
0.00%
0/65 • Baseline up to 10 months
|
|
Metabolism and nutrition disorders
Decreased appetite
|
1.6%
1/64 • Baseline up to 10 months
|
4.6%
3/65 • Baseline up to 10 months
|
|
Nervous system disorders
Headache
|
7.8%
5/64 • Baseline up to 10 months
|
3.1%
2/65 • Baseline up to 10 months
|
|
Nervous system disorders
Lethargy
|
3.1%
2/64 • Baseline up to 10 months
|
0.00%
0/65 • Baseline up to 10 months
|
|
Nervous system disorders
Somnolence
|
3.1%
2/64 • Baseline up to 10 months
|
0.00%
0/65 • Baseline up to 10 months
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/64 • Baseline up to 10 months
|
3.1%
2/65 • Baseline up to 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.2%
4/64 • Baseline up to 10 months
|
1.5%
1/65 • Baseline up to 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
1.6%
1/64 • Baseline up to 10 months
|
3.1%
2/65 • Baseline up to 10 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
3.1%
2/64 • Baseline up to 10 months
|
0.00%
0/65 • Baseline up to 10 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
4.7%
3/64 • Baseline up to 10 months
|
3.1%
2/65 • Baseline up to 10 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER