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Trial record 18 of 83 for:    lewy body dementia

A Study of E2020 in Patients With Dementia With Lewy Bodies (DLB), Followed by a Long-term Extension Phase

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ClinicalTrials.gov Identifier: NCT01278407
Recruitment Status : Completed
First Posted : January 17, 2011
Results First Posted : November 30, 2015
Last Update Posted : February 2, 2016
Sponsor:
Information provided by (Responsible Party):
Eisai Inc. ( Eisai Co., Ltd. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Dementia With Lewy Bodies (DLB)
Interventions Drug: Donepezil 5 mg
Drug: Donepezil 10 mg
Drug: Donepezil matched placebo
Enrollment 142
Recruitment Details  
Pre-assignment Details In the 'Placebo to Donepezil (5+10 mg) Extension Phase' arm, 37 of 46 participants started active treatment at Week 16.
Arm/Group Title Placebo - Confirmatory Phase Donepezil 5 mg - Confirmatory Phase Donepezil 10 mg - Confirmatory Phase Placebo to Donepezil (5 +10 mg) - Extension Phase Donepezil (5 +10 mg) - Extension Phase
Hide Arm/Group Description Participants received donepezil matched placebo tablets orally, once daily for 12 weeks in the confirmatory phase. Participants received donepezil tablets orally, once daily for 12 weeks. Treatment began with 3 mg for 2 weeks, and then the dose was increased to 5 mg for 10 weeks in the confirmatory phase. Participants received donepezil tablets orally, once daily for 12 weeks. Treatment began with 3 mg for 2 weeks, and then the dose was increased to 5 mg for 4 weeks. Thereafter, the dose was increased to 10 mg for 6 weeks in the confirmatory phase. Participants previously receiving donepezil matched placebo up to Week 12 in the Confirmatory Phase, continued placebo until Week 16 (at the beginning of the Extension Phase). Participants received 3 mg of donepezil, and the dose was then increased to 5 mg at Week 18 and to 10 mg at Week 24. After Week 24, dose reduction to 5 mg was allowed if continuation at 10 mg caused any safety concerns. Participants previously receiving donepezil (5 mg or 10 mg) up to Week 12 in the Confirmatory Phase, maintained allocated treatment and dosages until Week 24. In the 5 mg group of the Confirmatory Phase, the dose was increased to 10 mg at Week 24. After Week 24, dose reduction to 5 mg was allowed if continuation at 10 mg caused any safety concerns.
Period Title: Confirmatory Phase
Started 46 47 49 0 0
Completed 37 31 43 0 0
Not Completed 9 16 6 0 0
Reason Not Completed
Adverse Event             5             10             1             0             0
Participant's Choice             3             5             3             0             0
Not Specified             1             1             2             0             0
Period Title: Extension Phase
Started 0 0 0 46 96
Completed 0 0 0 34 66
Not Completed 0 0 0 12 30
Reason Not Completed
Adverse Event             0             0             0             7             16
Participant's Choice             0             0             0             4             11
Not Specified             0             0             0             1             3
Arm/Group Title Placebo - Confirmatory Phase Donepezil 5 mg - Confirmatory Phase Donepezil 10 mg - Confirmatory Phase Total
Hide Arm/Group Description Participants received donepezil matched placebo tablets orally, once daily for 12 weeks in the confirmatory phase. Participants received donepezil tablets orally, once daily for 12 weeks. Treatment began with 3 mg for 2 weeks, and then the dose was increased to 5 mg for 10 weeks in the confirmatory phase. Participants received donepezil tablets orally, once daily for 12 weeks. Treatment began with 3 mg for 2 weeks, and then the dose was increased to 5 mg for 4 weeks. Thereafter, the dose was increased to 10 mg for 6 weeks in the confirmatory phase. Total of all reporting groups
Overall Number of Baseline Participants 44 45 49 138
Hide Baseline Analysis Population Description
The data is based on Full Analysis Set, defined as all the randomized patients who received the study drug at least once and had valid efficacy assessment data at more than one point.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 44 participants 45 participants 49 participants 138 participants
77.2  (6.1) 78.8  (5.1) 77.7  (6.8) 77.9  (6.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 45 participants 49 participants 138 participants
Female
27
  61.4%
25
  55.6%
28
  57.1%
80
  58.0%
Male
17
  38.6%
20
  44.4%
21
  42.9%
58
  42.0%
Mini-Mental State Examination (MMSE) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Unit on a scale
Number Analyzed 44 participants 45 participants 49 participants 138 participants
20.3  (4.2) 20.6  (4.1) 20.3  (4.8) 20.4  (4.3)
[1]
Measure Description: The score ranged from 0 to 30, with a higher score indicating better function.
1.Primary Outcome
Title Change From Baseline in Mini-Mental State Examination (MMSE) Score
Hide Description The MMSE was used to measure cognitive impairment. The MMSE can evaluate overall cognitive function, and is widely used for the assessment of cognitive impairment in dementia patients. The questionnaire consists of 11 items, and each item aims to evaluate different cognitive domains such as orientation, memory, attention, and construction. The score ranged from 0 to 30, with a higher score indicating better function. A positive change score indicated improvement from baseline. Data are presented as change from baseline in mean MMSE +/- standard deviation.
Time Frame Week 12 for Confirmatory Phase
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: Efficacy was analyzed in the full analysis set, including the randomized participants who received the study drug at least once and had valid efficacy assessment data at more than one point.
Arm/Group Title Placebo - Confirmatory Phase Donepezil 5 mg - Confirmatory Phase Donepezil 10 mg - Confirmatory Phase
Hide Arm/Group Description:
Participants received donepezil matched placebo tablets orally, once daily for 12 weeks in the confirmatory phase.
Participants received donepezil tablets orally, once daily for 12 weeks. Treatment began with 3 mg for 2 weeks, and then the dose was increased to 5 mg for 10 weeks in the confirmatory phase.
Participants received donepezil tablets orally, once daily for 12 weeks. Treatment began with 3 mg for 2 weeks, and then the dose was increased to 5 mg for 4 weeks. Thereafter, the dose was increased to 10 mg for 6 weeks in the confirmatory phase.
Overall Number of Participants Analyzed 44 43 49
Mean (Standard Deviation)
Unit of Measure: Units on a scale
0.6  (3.0) 1.4  (3.4) 2.2  (2.9)
2.Primary Outcome
Title Change From Baseline in Neuropsychiatric Inventory (NPI-2) Score
Hide Description The NPI was a questionnaire that quantified psychiatric symptoms and behavioral disorders in dementia. A total of 12 items (the original NPI-10 consisting of 10 behavioral domains: delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability, and aberrant motor behavior, supplemented by 2 dementia with Lewy bodies (DLB)-relevant domains of sleep, and cognitive fluctuation [reported as cognitive fluctuation inventory]) were assessed. The score of each item was calculated as frequency (scale: 1=occasionally to 4=very frequently) x Severity (scale: 1=Mild to 3=Severe). The NPI-2 was calculated as the sum of the scores for hallucinations and cognitive fluctuation, to yield a possible total score of 0 to 24. Lower score=less severity. A negative change score from baseline indicated improvement. Data are presented as change from baseline in mean NPI-2 +/- standard deviation.
Time Frame Week 12 for Confirmatory Phase
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: Efficacy was analyzed in the full analysis set, including the randomized participants who received the study drug at least once and had valid efficacy assessment data at more than one point.
Arm/Group Title Placebo - Confirmatory Phase Donepezil 5 mg - Confirmatory Phase Donepezil 10 mg - Confirmatory Phase
Hide Arm/Group Description:
Participants received donepezil matched placebo tablets orally, once daily for 12 weeks in the confirmatory phase.
Participants received donepezil tablets orally, once daily for 12 weeks. Treatment began with 3 mg for 2 weeks, and then the dose was increased to 5 mg for 10 weeks in the confirmatory phase.
Participants received donepezil tablets orally, once daily for 12 weeks. Treatment began with 3 mg for 2 weeks, and then the dose was increased to 5 mg for 4 weeks. Thereafter, the dose was increased to 10 mg for 6 weeks in the confirmatory phase.
Overall Number of Participants Analyzed 44 45 49
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-2.0  (4.2) -1.7  (4.3) -2.9  (4.7)
Time Frame For each patient from first dose of study drug administration up to 30 days from last dose of study drug or up to approximately Week 12 for Confirmatory Phase and Week 52 for Extension Phase
Adverse Event Reporting Description Safety Analysis Set: The safety analysis set comprised of all patients who received at least one dose and had a postbaseline safety assessment. In the 'Placebo to Donepezil (5+10 mg) Extension Phase' arm, 37 of 46 participants started active treatment at Week 16.
 
Arm/Group Title Placebo - Confirmatory Phase Donepezil 5 mg - Confirmatory Phase Donepezil 10 mg - Confirmatory Phase Placebo to Donepezil (5 +10 mg) - Extension Phase Donepezil (5 +10 mg) - Extension Phase
Hide Arm/Group Description Participants received donepezil matched placebo tablets orally, once daily for 12 weeks in the confirmatory phase. Participants received donepezil tablets orally, once daily for 12 weeks. Treatment began with 3 mg for 2 weeks, and then the dose was increased to 5 mg for 10 weeks in the confirmatory phase. Participants received donepezil tablets orally, once daily for 12 weeks. Treatment began with 3 mg for 2 weeks, and then the dose was increased to 5 mg for 4 weeks. Thereafter, the dose was increased to 10 mg for 6 weeks in the confirmatory phase. Participants previously receiving donepezil matched placebo up to Week 12 in the Confirmatory Phase, continued placebo until Week 16 (at the beginning of the Extension Phase). Participants received 3 mg of donepezil, and the dose was then increased to 5 mg at Week 18 and to 10 mg at Week 24. After Week 24, dose reduction to 5 mg was allowed if continuation at 10 mg caused any safety concerns. Participants previously receiving donepezil (5 mg or 10 mg) up to Week 12 in the Confirmatory Phase, maintained allocated treatment and dosages until Week 24. In the 5 mg group of the Confirmatory Phase, the dose was increased to 10 mg at Week 24. After Week 24, dose reduction to 5 mg was allowed if continuation at 10 mg caused any safety concerns.
All-Cause Mortality
Placebo - Confirmatory Phase Donepezil 5 mg - Confirmatory Phase Donepezil 10 mg - Confirmatory Phase Placebo to Donepezil (5 +10 mg) - Extension Phase Donepezil (5 +10 mg) - Extension Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo - Confirmatory Phase Donepezil 5 mg - Confirmatory Phase Donepezil 10 mg - Confirmatory Phase Placebo to Donepezil (5 +10 mg) - Extension Phase Donepezil (5 +10 mg) - Extension Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/46 (10.87%)   4/47 (8.51%)   1/49 (2.04%)   9/37 (24.32%)   12/96 (12.50%) 
Blood and lymphatic system disorders           
Hypertension * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  0/37 (0.00%)  1/96 (1.04%) 
Cardiac disorders           
Myocardial infarction * 1  1/46 (2.17%)  0/47 (0.00%)  0/49 (0.00%)  1/37 (2.70%)  0/96 (0.00%) 
Eye disorders           
Cataract * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  1/37 (2.70%)  0/96 (0.00%) 
Gastrointestinal disorders           
Decreased appetite * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  0/37 (0.00%)  1/96 (1.04%) 
Inguinal hernia * 1  1/46 (2.17%)  0/47 (0.00%)  0/49 (0.00%)  1/37 (2.70%)  0/96 (0.00%) 
Intestinal obstruction * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  0/37 (0.00%)  1/96 (1.04%) 
Nausea * 1  0/46 (0.00%)  1/47 (2.13%)  0/49 (0.00%)  0/37 (0.00%)  1/96 (1.04%) 
Vomiting * 1  0/46 (0.00%)  0/47 (0.00%)  1/49 (2.04%)  0/37 (0.00%)  1/96 (1.04%) 
General disorders           
Pyrexia * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  0/37 (0.00%)  1/96 (1.04%) 
Infections and infestations           
Bronchitis * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  0/37 (0.00%)  1/96 (1.04%) 
Pneumonia * 1  0/46 (0.00%)  1/47 (2.13%)  0/49 (0.00%)  0/37 (0.00%)  2/96 (2.08%) 
Injury, poisoning and procedural complications           
Femoral neck fracture * 1  1/46 (2.17%)  0/47 (0.00%)  0/49 (0.00%)  1/37 (2.70%)  0/96 (0.00%) 
Femur fracture * 1  0/46 (0.00%)  1/47 (2.13%)  0/49 (0.00%)  0/37 (0.00%)  1/96 (1.04%) 
Spinal compression fracture * 1  1/46 (2.17%)  0/47 (0.00%)  0/49 (0.00%)  2/37 (5.41%)  0/96 (0.00%) 
Metabolism and nutrition disorders           
Hyponatraemia * 1  0/46 (0.00%)  1/47 (2.13%)  0/49 (0.00%)  0/37 (0.00%)  1/96 (1.04%) 
Musculoskeletal and connective tissue disorders           
Osteoarthritis * 1  0/46 (0.00%)  1/47 (2.13%)  0/49 (0.00%)  0/37 (0.00%)  1/96 (1.04%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Gastric cancer * 1  1/46 (2.17%)  0/47 (0.00%)  0/49 (0.00%)  1/37 (2.70%)  0/96 (0.00%) 
Nervous system disorders           
Loss of consciousness * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  1/37 (2.70%)  1/96 (1.04%) 
Psychiatric disorders           
Hallucination * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  0/37 (0.00%)  1/96 (1.04%) 
Hallucination, visual * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  0/37 (0.00%)  1/96 (1.04%) 
Insomnia * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  0/37 (0.00%)  1/96 (1.04%) 
Paranoia * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  0/37 (0.00%)  1/96 (1.04%) 
Renal and urinary disorders           
Renal impairment * 1  0/46 (0.00%)  0/47 (0.00%)  1/49 (2.04%)  0/37 (0.00%)  1/96 (1.04%) 
Respiratory, thoracic and mediastinal disorders           
Asphyxia * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  1/37 (2.70%)  0/96 (0.00%) 
Skin and subcutaneous tissue disorders           
Decubitus ulcer * 1  0/46 (0.00%)  1/47 (2.13%)  0/49 (0.00%)  0/37 (0.00%)  1/96 (1.04%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA version 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo - Confirmatory Phase Donepezil 5 mg - Confirmatory Phase Donepezil 10 mg - Confirmatory Phase Placebo to Donepezil (5 +10 mg) - Extension Phase Donepezil (5 +10 mg) - Extension Phase
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   23/46 (50.00%)   18/47 (38.30%)   17/49 (34.69%)   31/37 (83.78%)   62/96 (64.58%) 
Cardiac disorders           
Angina pectoris * 1  1/46 (2.17%)  0/47 (0.00%)  0/49 (0.00%)  2/37 (5.41%)  2/96 (2.08%) 
Eye disorders           
Conjunctivitis * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  2/37 (5.41%)  1/96 (1.04%) 
Gastrointestinal disorders           
Diarrhoea * 1  2/46 (4.35%)  1/47 (2.13%)  1/49 (2.04%)  4/37 (10.81%)  6/96 (6.25%) 
Constipation * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  3/37 (8.11%)  5/96 (5.21%) 
Nausea * 1  1/46 (2.17%)  2/47 (4.26%)  1/49 (2.04%)  3/37 (8.11%)  4/96 (4.17%) 
Abdominal discomfort * 1  1/46 (2.17%)  0/47 (0.00%)  0/49 (0.00%)  2/37 (5.41%)  2/96 (2.08%) 
Gastritis * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  2/37 (5.41%)  1/96 (1.04%) 
Abdominal pain upper * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  2/37 (5.41%)  0/96 (0.00%) 
Dyspepsia * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  2/37 (5.41%)  0/96 (0.00%) 
General disorders           
Pyrexia * 1  0/46 (0.00%)  0/47 (0.00%)  3/49 (6.12%)  0/37 (0.00%)  3/96 (3.13%) 
Irritability * 1  1/46 (2.17%)  1/47 (2.13%)  0/49 (0.00%)  2/37 (5.41%)  2/96 (2.08%) 
Oedema peripheral * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  2/37 (5.41%)  1/96 (1.04%) 
Hepatobiliary disorders           
Hepatic function abnormal * 1  2/46 (4.35%)  0/47 (0.00%)  0/49 (0.00%)  3/37 (8.11%)  0/96 (0.00%) 
Infections and infestations           
Nasopharyngitis * 1  7/46 (15.22%)  4/47 (8.51%)  2/49 (4.08%)  18/37 (48.65%)  17/96 (17.71%) 
Bronchitis * 1  1/46 (2.17%)  0/47 (0.00%)  0/49 (0.00%)  2/37 (5.41%)  0/96 (0.00%) 
Injury, poisoning and procedural complications           
Contusion * 1  4/46 (8.70%)  0/47 (0.00%)  1/49 (2.04%)  6/37 (16.22%)  7/96 (7.29%) 
Investigations           
Glucose urine present * 1  0/46 (0.00%)  0/47 (0.00%)  1/49 (2.04%)  1/37 (2.70%)  5/96 (5.21%) 
Blood creatine phosphokinase increased * 1  0/46 (0.00%)  1/47 (2.13%)  2/49 (4.08%)  0/37 (0.00%)  5/96 (5.21%) 
Weight decreased * 1  2/46 (4.35%)  1/47 (2.13%)  0/49 (0.00%)  2/37 (5.41%)  2/96 (2.08%) 
Lymphocyte count decreased * 1  1/46 (2.17%)  0/47 (0.00%)  0/49 (0.00%)  2/37 (5.41%)  1/96 (1.04%) 
Metabolism and nutrition disorders           
Decreased appetite * 1  1/46 (2.17%)  3/47 (6.38%)  2/49 (4.08%)  2/37 (5.41%)  5/96 (5.21%) 
Diabetes mellitus * 1  1/46 (2.17%)  0/47 (0.00%)  0/49 (0.00%)  2/37 (5.41%)  2/96 (2.08%) 
Musculoskeletal and connective tissue disorders           
Muscle spasms * 1  0/46 (0.00%)  1/47 (2.13%)  2/49 (4.08%)  2/37 (5.41%)  5/96 (5.21%) 
Spinal osteoarthritis * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  2/37 (5.41%)  0/96 (0.00%) 
Nervous system disorders           
Parkinsonism * 1  2/46 (4.35%)  2/47 (4.26%)  4/49 (8.16%)  5/37 (13.51%)  12/96 (12.50%) 
Dizziness * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  3/37 (8.11%)  1/96 (1.04%) 
Somnolence * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  2/37 (5.41%)  0/96 (0.00%) 
Psychiatric disorders           
Agitation * 1  2/46 (4.35%)  1/47 (2.13%)  0/49 (0.00%)  2/37 (5.41%)  3/96 (3.13%) 
Insomnia * 1  0/46 (0.00%)  2/47 (4.26%)  0/49 (0.00%)  0/37 (0.00%)  5/96 (5.21%) 
Sleep disorder * 1  2/46 (4.35%)  1/47 (2.13%)  0/49 (0.00%)  3/37 (8.11%)  1/96 (1.04%) 
Renal and urinary disorders           
Pollakiuria * 1  0/46 (0.00%)  3/47 (6.38%)  0/49 (0.00%)  0/37 (0.00%)  3/96 (3.13%) 
Skin and subcutaneous tissue disorders           
Eczema * 1  2/46 (4.35%)  0/47 (0.00%)  0/49 (0.00%)  4/37 (10.81%)  1/96 (1.04%) 
Rash * 1  0/46 (0.00%)  1/47 (2.13%)  1/49 (2.04%)  2/37 (5.41%)  2/96 (2.08%) 
Vascular disorders           
Hypertension * 1  0/46 (0.00%)  0/47 (0.00%)  0/49 (0.00%)  2/37 (5.41%)  1/96 (1.04%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA version 15.0
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
Name/Title: Masaki Nakagawa
Organization: Eisai Co., Ltd.
Phone: +81-3-3817-5245 ext 5245
Responsible Party: Eisai Inc. ( Eisai Co., Ltd. )
ClinicalTrials.gov Identifier: NCT01278407     History of Changes
Other Study ID Numbers: E2020-J081-341
First Submitted: January 14, 2011
First Posted: January 17, 2011
Results First Submitted: October 27, 2015
Results First Posted: November 30, 2015
Last Update Posted: February 2, 2016