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Trial record 73 of 332 for:    DONEPEZIL

Comparison of 23 mg Donepezil Sustained Release (SR) to 10 mg Donepezil Immediate Release (IR) in Patients With Moderate to Severe Alzheimer's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00478205
Recruitment Status : Completed
First Posted : May 24, 2007
Results First Posted : February 5, 2013
Last Update Posted : July 11, 2014
Sponsor:
Collaborator:
Eisai Limited
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 Alzheimer's Disease
Interventions Drug: Aricept (donepezil SR 23 mg)
Drug: Aricept (donepezil IR 10 mg)
Enrollment 1467
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Donepezil SR 23 mg Donepezil IR 10 mg
Hide Arm/Group Description Donepezil sustained release (SR) 23 mg in combination with placebo corresponding to donepezil IR 10 mg ; dosing continued for a 24-week treatment period. Donepezil immediate release (IR) 10 mg in combination with placebo corresponding to donepezil SR 23 mg; dosing continued for a 24-week treatment period.
Period Title: Overall Study
Started 981 486
Completed 685 399
Not Completed 296 87
Reason Not Completed
Adverse Event             182             39
Medication Non-compliance             9             4
Protocol Violation             15             5
Request of Investigator or Sponsor             4             5
Withdrawal by Subject             61             22
Lack of Efficacy             1             0
Not specified             24             12
Arm/Group Title Donepezil SR 23 mg Donepezil IR 10 mg Total
Hide Arm/Group Description Donepezil sustained release (SR) 23 mg in combination with placebo corresponding to donepezil IR 10 mg ; dosing continued for a 24-week treatment period. Donepezil immediate release (IR) 10 mg in combination with placebo corresponding to donepezil SR 23 mg; dosing continued for a 24-week treatment period. Total of all reporting groups
Overall Number of Baseline Participants 963 471 1434
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 963 participants 471 participants 1434 participants
73.9  (8.53) 73.8  (8.56) 73.8  (8.53)
[1]
Measure Description: Safety Population
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 963 participants 471 participants 1434 participants
Female
607
  63.0%
294
  62.4%
901
  62.8%
Male
356
  37.0%
177
  37.6%
533
  37.2%
[1]
Measure Description: Safety Population: All patients randomized who took at least one dose of study medication and who had at least one postbaseline safety assessment.
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 963 participants 471 participants 1434 participants
Black 22 9 31
White 708 346 1054
Hispanic 67 26 93
Native American 0 0 0
Asian/Pacific 161 87 248
Other 5 3 8
[1]
Measure Description: Race (Safety Population)
1.Primary Outcome
Title Change From Baseline to Week 24 in SIB Total Score
Hide Description The SIB is an assessment of cognitive dysfunction across nine domains such as memory, language, and orientation. The score ranges from 0 (worst) to 100 (best). This outcome was calculated using the LOCF (last observation carried forward) method.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: All Randomized patients in Safety Population and Severe Impairment Battery (SIB) or Clinician Interview-Based Impression of Severity Plus Caregiver Input (CIBIS+) data available at Baseline and SIB or Clinician Interview-Based Impression of Change Plus caregiver Input (CIBIC+ ) data available post-Baseline; LOCF
Arm/Group Title Donepezil SR 23 mg Donepezil IR 10 mg
Hide Arm/Group Description:
Donepezil sustained release (SR) 23 mg in combination with placebo corresponding to donepezil IR 10 mg ; dosing continued for a 24-week treatment period.
Donepezil immediate release (IR) 10 mg in combination with placebo corresponding to donepezil SR 23 mg; dosing continued for a 24-week treatment period.
Overall Number of Participants Analyzed 909 462
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
2.6  (0.58) 0.4  (0.66)
2.Primary Outcome
Title Overall Change From Baseline in Modified CIBIC+ to Week 24
Hide Description The CIBIC+ is a rating scale derived from an interview with the patient and caregiver with an independent rater designed to measure several domains of patient function, such as mental/cognitive state, behavior, and activities of daily living. The scores range from 1 (marked improvement) to 7 (marked worsening).
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population, LOCF
Arm/Group Title Donepezil SR 23 mg Donepezil IR 10 mg
Hide Arm/Group Description:
Donepezil sustained release (SR) 23 mg in combination with placebo corresponding to donepezil IR 10 mg ; dosing continued for a 24-week treatment period.
Donepezil immediate release (IR) 10 mg in combination with placebo corresponding to donepezil SR 23 mg; dosing continued for a 24-week treatment period.
Overall Number of Participants Analyzed 909 462
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
4.23  (1.07) 4.29  (1.07)
3.Secondary Outcome
Title Change From Baseline to Week 24 in ADCS-ADL Total Score
Hide Description The ADCS-ADL (Alzhemier's Disease Cooperative Study-Activities of Daily Living) is a 19-item assessment scale used to measure a patient's basic functional abilities, such as walking, grooming, and bathing.Scores range from 0 to 54, with a higher score indicating greater functional ability.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population, LOCF
Arm/Group Title Donepezil SR 23 mg Donepezil IR 10 mg
Hide Arm/Group Description:
Donepezil sustained release (SR) 23 mg in combination with placebo corresponding to donepezil IR 10 mg ; dosing continued for a 24-week treatment period.
Donepezil immediate release (IR) 10 mg in combination with placebo corresponding to donepezil SR 23 mg; dosing continued for a 24-week treatment period.
Overall Number of Participants Analyzed 909 462
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-1.2  (6.83) -1.2  (6.78)
4.Secondary Outcome
Title Change From Baseline to Week 24 in MMSE Total Score
Hide Description The MMSE (Mini-Mental State Examination) is a 30-item test that evaluates 5 domains of cognitive function (orientation to time and place, immediate and delayed recall, attention, calculation, and language). The scores range from 0 (most impaired) to 30 (no impaiment).
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population, LOCF
Arm/Group Title Donepezil SR 23 mg Donepezil IR 10 mg
Hide Arm/Group Description:
Donepezil sustained release (SR) 23 mg in combination with placebo corresponding to donepezil IR 10 mg ; dosing continued for a 24-week treatment period.
Donepezil immediate release (IR) 10 mg in combination with placebo corresponding to donepezil SR 23 mg; dosing continued for a 24-week treatment period.
Overall Number of Participants Analyzed 909 462
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
0.6  (2.93) 0.4  (3.20)
Time Frame All adverse events (AEs) were recorded from the time of informed consent until after the Final Visit or Early Termination.
Adverse Event Reporting Description Serious adverse events (SAEs) were monitored through the termination visit and through 30 days after study drug discontinuation, whichever was longer.
 
Arm/Group Title Donepezil SR 23 mg Donepezil IR 10 mg
Hide Arm/Group Description Donepezil sustained release (SR) 23 mg in combination with placebo corresponding to donepezil IR 10 mg ; dosing continued for a 24-week treatment period. Donepezil immediate release (IR) 10 mg in combination with placebo corresponding to donepezil SR 23 mg; dosing continued for a 24-week treatment period.
All-Cause Mortality
Donepezil SR 23 mg Donepezil IR 10 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Donepezil SR 23 mg Donepezil IR 10 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   80/963 (8.31%)   45/471 (9.55%) 
Blood and lymphatic system disorders     
Anaemia  1  1/963 (0.10%)  0/471 (0.00%) 
Leukocytosis  1  1/963 (0.10%)  0/471 (0.00%) 
Cardiac disorders     
Acute coronary syndrome  1  1/963 (0.10%)  0/471 (0.00%) 
Acute myocardial infarction  1  0/963 (0.00%)  1/471 (0.21%) 
Angina pectoris  1  1/963 (0.10%)  0/471 (0.00%) 
Atrial fibrillation  1  4/963 (0.42%)  1/471 (0.21%) 
Bradycardia  1  4/963 (0.42%)  0/471 (0.00%) 
Cardiac failure  1  0/963 (0.00%)  1/471 (0.21%) 
Cardiac failure congestive  1  1/963 (0.10%)  0/471 (0.00%) 
Cardio-respiratory arrest  1  1/963 (0.10%)  0/471 (0.00%) 
Cardiopulmonary failure  1  1/963 (0.10%)  0/471 (0.00%) 
Cardiovascular disorder  1  1/963 (0.10%)  0/471 (0.00%) 
Coronary artery occlusion  1  1/963 (0.10%)  0/471 (0.00%) 
Myocardial infarction  1  2/963 (0.21%)  1/471 (0.21%) 
Myocardial ischaemia  1  0/963 (0.00%)  1/471 (0.21%) 
Tachycardia  1  0/963 (0.00%)  1/471 (0.21%) 
Ventricular tachycardia  1  1/963 (0.10%)  0/471 (0.00%) 
Eye disorders     
Diplopia  1  0/963 (0.00%)  1/471 (0.21%) 
Gastrointestinal disorders     
Abdominal discomfort  1  1/963 (0.10%)  0/471 (0.00%) 
Abdominal pain  1  1/963 (0.10%)  0/471 (0.00%) 
Diarrhoea  1  4/963 (0.42%)  0/471 (0.00%) 
Diarrhoea haemorrhagic  1  1/963 (0.10%)  0/471 (0.00%) 
Dyspepsia  1  1/963 (0.10%)  0/471 (0.00%) 
Gastric ulcer haemorrhage  1  1/963 (0.10%)  0/471 (0.00%) 
Gastritis  1  1/963 (0.10%)  0/471 (0.00%) 
Gastrointestinal haemorrhage  1  2/963 (0.21%)  0/471 (0.00%) 
Gastrooesophageal reflux disease  1  2/963 (0.21%)  0/471 (0.00%) 
Haematochezia  1  1/963 (0.10%)  0/471 (0.00%) 
Hiatus hernia  1  1/963 (0.10%)  0/471 (0.00%) 
Inguinal hernia  1  0/963 (0.00%)  1/471 (0.21%) 
Nausea  1  1/963 (0.10%)  0/471 (0.00%) 
Oesophageal ulcer  1  1/963 (0.10%)  0/471 (0.00%) 
Rectal haemorrhage  1  2/963 (0.21%)  0/471 (0.00%) 
Small intestinal obstruction  1  0/963 (0.00%)  1/471 (0.21%) 
Vomiting  1  3/963 (0.31%)  0/471 (0.00%) 
General disorders     
Asthenia  1  2/963 (0.21%)  0/471 (0.00%) 
Drowning  1  1/963 (0.10%)  0/471 (0.00%) 
General physical health deterioration  1  1/963 (0.10%)  0/471 (0.00%) 
Hypothermia  1  1/963 (0.10%)  2/471 (0.42%) 
Irritability  1  0/963 (0.00%)  1/471 (0.21%) 
Pyrexia  1  1/963 (0.10%)  0/471 (0.00%) 
Hepatobiliary disorders     
Bile duct stenosis  1  1/963 (0.10%)  0/471 (0.00%) 
Bile duct stone  1  1/963 (0.10%)  0/471 (0.00%) 
Cholangitis acute  1  1/963 (0.10%)  0/471 (0.00%) 
Cholecystitis acute  1  0/963 (0.00%)  1/471 (0.21%) 
Cholecystitis chronic  1  1/963 (0.10%)  0/471 (0.00%) 
Cholelithiasis  1  1/963 (0.10%)  1/471 (0.21%) 
Infections and infestations     
Bronchitis  1  1/963 (0.10%)  0/471 (0.00%) 
Cellulitis  1  0/963 (0.00%)  1/471 (0.21%) 
Diverticulitis  1  1/963 (0.10%)  0/471 (0.00%) 
Gastroenteritis  1  0/963 (0.00%)  1/471 (0.21%) 
Gastrointestinal infection  1  1/963 (0.10%)  0/471 (0.00%) 
Pneumonia  1  3/963 (0.31%)  3/471 (0.64%) 
Sepsis  1  1/963 (0.10%)  1/471 (0.21%) 
Septic shock  1  0/963 (0.00%)  1/471 (0.21%) 
Urinary tract infection  1  6/963 (0.62%)  2/471 (0.42%) 
Injury, poisoning and procedural complications     
Burns first degree  1  1/963 (0.10%)  0/471 (0.00%) 
Burns second degree  1  1/963 (0.10%)  0/471 (0.00%) 
Contusion  1  1/963 (0.10%)  0/471 (0.00%) 
Facial bones fracture  1  2/963 (0.21%)  0/471 (0.00%) 
Fall  1  6/963 (0.62%)  2/471 (0.42%) 
Femoral neck fracture  1  1/963 (0.10%)  0/471 (0.00%) 
Femur fracture  1  4/963 (0.42%)  1/471 (0.21%) 
Hip fracture  1  1/963 (0.10%)  0/471 (0.00%) 
Neck injury  1  1/963 (0.10%)  0/471 (0.00%) 
Overdose  1  0/963 (0.00%)  1/471 (0.21%) 
Pelvic fracture  1  0/963 (0.00%)  1/471 (0.21%) 
Procedural complication  1  1/963 (0.10%)  0/471 (0.00%) 
Rib fracture  1  0/963 (0.00%)  1/471 (0.21%) 
Road traffic accident  1  1/963 (0.10%)  0/471 (0.00%) 
Skin laceration  1  1/963 (0.10%)  1/471 (0.21%) 
Subdural haematoma  1  2/963 (0.21%)  0/471 (0.00%) 
Upper limb fracture  1  0/963 (0.00%)  1/471 (0.21%) 
Wrist fracture  1  1/963 (0.10%)  0/471 (0.00%) 
Investigations     
Blood pressure increased  1  0/963 (0.00%)  1/471 (0.21%) 
Electrocardiogram QT prolonged  1  1/963 (0.10%)  0/471 (0.00%) 
Weight decreased  1  1/963 (0.10%)  0/471 (0.00%) 
Metabolism and nutrition disorders     
Anorexia  1  0/963 (0.00%)  1/471 (0.21%) 
Dehydration  1  3/963 (0.31%)  0/471 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthritis  1  1/963 (0.10%)  0/471 (0.00%) 
Back pain  1  2/963 (0.21%)  1/471 (0.21%) 
Mobility decreased  1  0/963 (0.00%)  1/471 (0.21%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Abdominal neoplasm  1  1/963 (0.10%)  0/471 (0.00%) 
Breast cancer  1  0/963 (0.00%)  1/471 (0.21%) 
Colon cancer  1  1/963 (0.10%)  0/471 (0.00%) 
Prostate cancer recurrent  1  0/963 (0.00%)  1/471 (0.21%) 
Nervous system disorders     
Balance disorder  1  1/963 (0.10%)  0/471 (0.00%) 
Cerebellar infarction  1  0/963 (0.00%)  1/471 (0.21%) 
Cerebrovascular accident  1  1/963 (0.10%)  1/471 (0.21%) 
Convulsion  1  0/963 (0.00%)  2/471 (0.42%) 
Dementia  1  0/963 (0.00%)  1/471 (0.21%) 
Dizziness  1  4/963 (0.42%)  1/471 (0.21%) 
Grand mal convulsion  1  1/963 (0.10%)  0/471 (0.00%) 
Headache  1  0/963 (0.00%)  1/471 (0.21%) 
Presyncope  1  3/963 (0.31%)  0/471 (0.00%) 
Somnolence  1  1/963 (0.10%)  0/471 (0.00%) 
Subarachnoid haemorrhage  1  0/963 (0.00%)  1/471 (0.21%) 
Syncope  1  2/963 (0.21%)  5/471 (1.06%) 
Thalamic infarction  1  0/963 (0.00%)  1/471 (0.21%) 
Transient ischaemic attack  1  0/963 (0.00%)  1/471 (0.21%) 
Unresponsive to stimuli  1  1/963 (0.10%)  0/471 (0.00%) 
Psychiatric disorders     
Abnormal behaviour  1  1/963 (0.10%)  0/471 (0.00%) 
Aggression  1  2/963 (0.21%)  4/471 (0.85%) 
Behavioural and psychiatric symptoms of dementia  1  1/963 (0.10%)  0/471 (0.00%) 
Confusional state  1  1/963 (0.10%)  3/471 (0.64%) 
Delusion  1  1/963 (0.10%)  1/471 (0.21%) 
Depression  1  0/963 (0.00%)  1/471 (0.21%) 
Hallucination  1  0/963 (0.00%)  1/471 (0.21%) 
Insomnia  1  0/963 (0.00%)  1/471 (0.21%) 
Mental status changes  1  2/963 (0.21%)  0/471 (0.00%) 
Paranoia  1  1/963 (0.10%)  0/471 (0.00%) 
Poriomania  1  1/963 (0.10%)  0/471 (0.00%) 
Suicide attempt  1  1/963 (0.10%)  0/471 (0.00%) 
Renal and urinary disorders     
Calculus ureteric  1  0/963 (0.00%)  1/471 (0.21%) 
Renal failure  1  0/963 (0.00%)  1/471 (0.21%) 
Renal failure acute  1  3/963 (0.31%)  0/471 (0.00%) 
Urinary retention  1  1/963 (0.10%)  0/471 (0.00%) 
Reproductive system and breast disorders     
Breast mass  1  1/963 (0.10%)  0/471 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  1/963 (0.10%)  0/471 (0.00%) 
Dyspnoea  1  2/963 (0.21%)  1/471 (0.21%) 
Pneumomediastinum  1  1/963 (0.10%)  0/471 (0.00%) 
Pneumonia aspiration  1  3/963 (0.31%)  0/471 (0.00%) 
Pulmonary embolism  1  2/963 (0.21%)  0/471 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  2/963 (0.21%)  0/471 (0.00%) 
Hypotension  1  2/963 (0.21%)  1/471 (0.21%) 
Orthostatic hypotension  1  1/963 (0.10%)  0/471 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v11.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Donepezil SR 23 mg Donepezil IR 10 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   233/963 (24.20%)   50/471 (10.62%) 
Gastrointestinal disorders     
Diarrhoea  1  76/963 (7.89%)  25/471 (5.31%) 
Nausea  1  113/963 (11.73%)  16/471 (3.40%) 
Vomiting  1  86/963 (8.93%)  12/471 (2.55%) 
Metabolism and nutrition disorders     
Anorexia  1  51/963 (5.30%)  8/471 (1.70%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v11.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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 Inc.
Organization: Eisai Call Center
Phone: 888-422-4743
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00478205     History of Changes
Other Study ID Numbers: E2020-G000-326
2006-004888-54 ( EudraCT Number )
First Submitted: May 22, 2007
First Posted: May 24, 2007
Results First Submitted: November 12, 2012
Results First Posted: February 5, 2013
Last Update Posted: July 11, 2014