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Evaluating The Efficacy And Safety Of Donepezil Hydrochloride (HCl) (Aricept) In Treating Cognitive Dysfunction Exhibited By Children With Down Syndrome

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ClinicalTrials.gov Identifier: NCT00570128
Recruitment Status : Completed
First Posted : December 10, 2007
Results First Posted : April 19, 2021
Last Update Posted : April 19, 2021
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Eisai Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Down Syndrome
Interventions Drug: Donepezil HCl
Drug: Placebo
Enrollment 129
Recruitment Details This study was conducted at 35 centers in the United States during the period of 16 November 2007 to 05 September 2008.
Pre-assignment Details  
Arm/Group Title Donepezil HCl Placebo
Hide Arm/Group Description 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). Liquid formulation matched to active treatment for oral administration.
Period Title: Overall Study
Started 64 65
Intent to Treat (ITT) Population 62 65
Completed 60 65
Not Completed 4 0
Reason Not Completed
Adverse Event             1             0
Lost to Follow-up             1             0
Withdrawal by Subject             2             0
Arm/Group Title Donepezil HCl Placebo Total
Hide Arm/Group Description 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). Liquid formulation matched to active treatment for oral administration. Total of all reporting groups
Overall Number of Baseline Participants 64 65 129
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 64 participants 65 participants 129 participants
13.0  (2.3) 13.0  (2.1) 13.0  (2.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 64 participants 65 participants 129 participants
Female
28
  43.8%
35
  53.8%
63
  48.8%
Male
36
  56.3%
30
  46.2%
66
  51.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 64 participants 65 participants 129 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   1.6%
4
   6.2%
5
   3.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
   4.7%
3
   4.6%
6
   4.7%
White
54
  84.4%
57
  87.7%
111
  86.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
6
   9.4%
1
   1.5%
7
   5.4%
1.Primary Outcome
Title 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)
Hide Description 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.
Time Frame Baseline, Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Donepezil HCl Placebo
Hide Arm/Group Description:
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).
Liquid formulation matched to active treatment for oral administration.
Overall Number of Participants Analyzed 61 65
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline 83.1  (15.5) 85.7  (15.8)
Mean change from baseline at Week 10 4.74  (9.2) 4.22  (8.5)
2.Secondary Outcome
Title 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)
Hide Description 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.
Time Frame Baseline, Week 4 and Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Donepezil HCl Placebo
Hide Arm/Group Description:
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).
Liquid formulation matched to active treatment for oral administration.
Overall Number of Participants Analyzed 61 65
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 61 participants 65 participants
83.1  (15.5) 85.7  (15.8)
Mean change from baseline at Week 4 Number Analyzed 54 participants 60 participants
1.5  (6.4) 2.6  (8.5)
Mean change from baseline at Week 10 Number Analyzed 55 participants 63 participants
5.1  (9.6) 4.2  (8.6)
3.Secondary Outcome
Title Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER) Total Score at Week 4 and 10-OC
Hide Description 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.
Time Frame Baseline, Week 4 and Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Donepezil HCl Placebo
Hide Arm/Group Description:
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).
Liquid formulation matched to active treatment for oral administration.
Overall Number of Participants Analyzed 62 64
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline Number Analyzed 62 participants 64 participants
20.7  (12.2) 21.6  (11.4)
Mean change from baseline at Week 4 Number Analyzed 56 participants 59 participants
1.2  (6.4) 0.9  (8.5)
Mean change from baseline at Week 10 Number Analyzed 56 participants 62 participants
2.6  (6.2) 1.9  (5.5)
4.Secondary Outcome
Title Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER) Total Score at Week 10-LOCF
Hide Description 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.
Time Frame Baseline, Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Donepezil HCl Placebo
Hide Arm/Group Description:
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).
Liquid formulation matched to active treatment for oral administration.
Overall Number of Participants Analyzed 62 64
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline 20.7  (12.2) 21.6  (11.4)
Mean change from baseline at Week 10 2.4  (6.0) 2.1  (5.5)
Time Frame Baseline up to 10 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Donepezil HCl Placebo
Hide Arm/Group Description 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). Liquid formulation matched to active treatment for oral administration.
All-Cause Mortality
Donepezil HCl Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/64 (0.00%)   0/65 (0.00%) 
Hide Serious Adverse Events
Donepezil HCl Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/64 (0.00%)   1/65 (1.54%) 
Infections and infestations     
Gastroenteritis  1  0/64 (0.00%)  1/65 (1.54%) 
Metabolism and nutrition disorders     
Dehydration  1  0/64 (0.00%)  1/65 (1.54%) 
1
Term from vocabulary, MedDRA 11.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Donepezil HCl Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   45/64 (70.31%)   42/65 (64.62%) 
Gastrointestinal disorders     
Abdominal pain, upper  1  2/64 (3.13%)  1/65 (1.54%) 
Constipation  1  0/64 (0.00%)  2/65 (3.08%) 
Diarrhea  1  11/64 (17.19%)  10/65 (15.38%) 
Fecal incontinence  1  2/64 (3.13%)  0/65 (0.00%) 
Nausea  1  5/64 (7.81%)  2/65 (3.08%) 
Vomiting  1  8/64 (12.50%)  2/65 (3.08%) 
General disorders     
Fatigue  1  1/64 (1.56%)  2/65 (3.08%) 
Pyrexia  1  2/64 (3.13%)  2/65 (3.08%) 
Infections and infestations     
Bronchitis  1  2/64 (3.13%)  0/65 (0.00%) 
Ear infection  1  1/64 (1.56%)  3/65 (4.62%) 
Gastroenteritis  1  0/64 (0.00%)  2/65 (3.08%) 
Gastroenteritis viral  1  2/64 (3.13%)  1/65 (1.54%) 
Nasopharyngitis  1  0/64 (0.00%)  4/65 (6.15%) 
Pharyngitis  1  3/64 (4.69%)  1/65 (1.54%) 
Sinusitis  1  1/64 (1.56%)  3/65 (4.62%) 
Upper respiratory tract infection  1  6/64 (9.38%)  5/65 (7.69%) 
Viral infection  1  2/64 (3.13%)  0/65 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  1/64 (1.56%)  3/65 (4.62%) 
Nervous system disorders     
Headache  1  5/64 (7.81%)  2/65 (3.08%) 
Lethargy  1  2/64 (3.13%)  0/65 (0.00%) 
Somnolence  1  2/64 (3.13%)  0/65 (0.00%) 
Psychiatric disorders     
Insomnia  1  0/64 (0.00%)  2/65 (3.08%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  4/64 (6.25%)  1/65 (1.54%) 
Nasal congestion  1  1/64 (1.56%)  2/65 (3.08%) 
Rhinitis allergic  1  2/64 (3.13%)  0/65 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash  1  3/64 (4.69%)  2/65 (3.08%) 
1
Term from vocabulary, MedDRA 11.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Eisai Medical Information
Organization: Eisai Inc.
Phone: +1-888-274-2378
EMail: esi_medinfo@eisai.com
Layout table for additonal information
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00570128    
Other Study ID Numbers: E2020-A001-219
A2501059 ( Other Identifier: Pfizer )
First Submitted: December 6, 2007
First Posted: December 10, 2007
Results First Submitted: March 29, 2013
Results First Posted: April 19, 2021
Last Update Posted: April 19, 2021