Trial Outcomes & Findings for An Efficacy and Safety Study of Galantamine for the Treatment of Patients With Alzheimer's Disease (NCT NCT00814801)
NCT ID: NCT00814801
Last Updated: 2014-04-17
Results Overview
ADAS-J cog is the Japanese version of the cognitive function subscale of the Alzheimer's disease assessment scale (ADAS). This scale is used to detect changes in cognitive function in individuals with Alzheimer disease on the basis of three domains: memory, language and behavior. The minimum score is zero (0) and means well cognitive function. The maximum total score is 70 points, and the larger the score, the more severe the degree of impairment.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
580 participants
Primary outcome timeframe
Baseline and 24 weeks
Results posted on
2014-04-17
Participant Flow
Participant milestones
| Measure |
Placebo Group
|
Galantamine Group 1
Galantamine 16 mg/day
|
Galantamine Group 2
Galantamine 24 mg/day
|
|---|---|---|---|
|
Overall Study
STARTED
|
194
|
192
|
194
|
|
Overall Study
COMPLETED
|
160
|
154
|
151
|
|
Overall Study
NOT COMPLETED
|
34
|
38
|
43
|
Reasons for withdrawal
| Measure |
Placebo Group
|
Galantamine Group 1
Galantamine 16 mg/day
|
Galantamine Group 2
Galantamine 24 mg/day
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
15
|
16
|
19
|
|
Overall Study
Withdrawal by Subject
|
9
|
11
|
14
|
|
Overall Study
Inappropriate as a subject
|
1
|
1
|
1
|
|
Overall Study
Change of patients for CIBIC plus-J
|
1
|
1
|
0
|
|
Overall Study
Missing or change of caregiver
|
6
|
2
|
4
|
|
Overall Study
Non-compliance
|
0
|
1
|
1
|
|
Overall Study
Other
|
2
|
6
|
4
|
Baseline Characteristics
An Efficacy and Safety Study of Galantamine for the Treatment of Patients With Alzheimer's Disease
Baseline characteristics by cohort
| Measure |
Placebo Group
n=191 Participants
|
Galantamine Group 1
n=191 Participants
Galantamine 16 mg/day
|
Galantamine Group 2
n=192 Participants
Galantamine 24 mg/day
|
Total
n=574 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
75.5 years
STANDARD_DEVIATION 7.6 • n=5 Participants
|
75.6 years
STANDARD_DEVIATION 8.4 • n=7 Participants
|
74.6 years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
75.2 years
STANDARD_DEVIATION 8.3 • n=4 Participants
|
|
Sex: Female, Male
Female
|
132 Participants
n=5 Participants
|
125 Participants
n=7 Participants
|
145 Participants
n=5 Participants
|
402 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
59 Participants
n=5 Participants
|
66 Participants
n=7 Participants
|
47 Participants
n=5 Participants
|
172 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline and 24 weeksPopulation: Intent-to-treat (ITT) population. Last observation carried forward (LOCF) end point.
ADAS-J cog is the Japanese version of the cognitive function subscale of the Alzheimer's disease assessment scale (ADAS). This scale is used to detect changes in cognitive function in individuals with Alzheimer disease on the basis of three domains: memory, language and behavior. The minimum score is zero (0) and means well cognitive function. The maximum total score is 70 points, and the larger the score, the more severe the degree of impairment.
Outcome measures
| Measure |
Placebo Group
n=191 Participants
|
Galantamine Group 1
n=191 Participants
Galantamine 16 mg/day
|
Galantamine Group 2
n=192 Participants
Galantamine 24 mg/day
|
|---|---|---|---|
|
Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog)
|
0.90 Scores on a scale
Standard Deviation 5.89
|
-0.58 Scores on a scale
Standard Deviation 5.87
|
-1.66 Scores on a scale
Standard Deviation 5.37
|
PRIMARY outcome
Timeframe: 24 weeksPopulation: Intent-to-treat (ITT) population. Last observation carried forward (LOCF) end point.
CIBIC plus-J is the Japanese version of the Clinician's Interview-based Impression of Change plus the caregiver's input (CIBIC plus). It is a seven-point categorical assessment scale for evaluating the efficacy of antidementia drugs, ranging from "markedly improved" to "markedly worse".
Outcome measures
| Measure |
Placebo Group
n=191 Participants
|
Galantamine Group 1
n=191 Participants
Galantamine 16 mg/day
|
Galantamine Group 2
n=192 Participants
Galantamine 24 mg/day
|
|---|---|---|---|
|
Distribution of Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J)
Markedly improved
|
0 patients
|
0 patients
|
1 patients
|
|
Distribution of Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J)
Moderately improved
|
7 patients
|
12 patients
|
4 patients
|
|
Distribution of Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J)
Minimally improved
|
36 patients
|
39 patients
|
32 patients
|
|
Distribution of Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J)
No change
|
64 patients
|
60 patients
|
73 patients
|
|
Distribution of Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J)
Minimally worse
|
62 patients
|
64 patients
|
61 patients
|
|
Distribution of Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J)
Moderately worse
|
22 patients
|
16 patients
|
20 patients
|
|
Distribution of Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J)
Markedly worse
|
0 patients
|
0 patients
|
1 patients
|
SECONDARY outcome
Timeframe: Baseline and 24 weeksPopulation: Intent-to-treat (ITT) population. Last observation carried forward (LOCF) end point.
Each of the 40 item of the DAD is scored as 1 point= Yes, 0 point= No, or non applicable= N/A. A total score (minimum=0; maximum=40) is the sum of points for each questions converted out 100. Items rated as Not Applicable (N/A) are not considered for the total score. The final score is a percentage that gives an appreciation of global function in activity of daily life (ADL). Higher scores represent less disability in ADL while lower scores indicate more dysfunction.
Outcome measures
| Measure |
Placebo Group
n=191 Participants
|
Galantamine Group 1
n=191 Participants
Galantamine 16 mg/day
|
Galantamine Group 2
n=192 Participants
Galantamine 24 mg/day
|
|---|---|---|---|
|
Change From Baseline in the Disability Assessment for Dementia (DAD)
|
-2.8 Scores on a scale
Standard Deviation 10.3
|
-1.0 Scores on a scale
Standard Deviation 9.4
|
-2.2 Scores on a scale
Standard Deviation 9.3
|
SECONDARY outcome
Timeframe: Baseline and 24 weeksPopulation: Intent-to-treat (ITT) population. Last observation carried forward (LOCF) end point.
Behave-AD is a CIBIC plus-J subscale that rates the patient's severity of psychotic symptoms. This four-point scale varies from 0 (=none) to 3 (= serious).
Outcome measures
| Measure |
Placebo Group
n=191 Participants
|
Galantamine Group 1
n=191 Participants
Galantamine 16 mg/day
|
Galantamine Group 2
n=192 Participants
Galantamine 24 mg/day
|
|---|---|---|---|
|
Change From Baseline in the Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD)
|
0.0 Scores on a scale
Standard Deviation 3.1
|
-0.2 Scores on a scale
Standard Deviation 4.2
|
-0.3 Scores on a scale
Standard Deviation 3.1
|
SECONDARY outcome
Timeframe: Baseline and 24 weeksPopulation: Intent-to-treat (ITT) population. Last observation carried forward (LOCF) end point.
MENFIS is a Clinician's Interview-Based Impression of Change (CIBIC) plus-Japan subscale that rates the patient's severity for mental function impairment. This seven-point scale varies from 0 (= absolutely no impairment) to 6 (=complete impairment).
Outcome measures
| Measure |
Placebo Group
n=191 Participants
|
Galantamine Group 1
n=191 Participants
Galantamine 16 mg/day
|
Galantamine Group 2
n=192 Participants
Galantamine 24 mg/day
|
|---|---|---|---|
|
Change From Baseline in the Mental Function Impairment Scale (MENFIS)
|
2.2 Scores on a scale
Standard Deviation 5.2
|
1.6 Scores on a scale
Standard Deviation 5.2
|
1.9 Scores on a scale
Standard Deviation 5.2
|
Adverse Events
Placebo Group
Serious events: 13 serious events
Other events: 146 other events
Deaths: 0 deaths
Galantamine Group 1
Serious events: 7 serious events
Other events: 154 other events
Deaths: 0 deaths
Galantamine Group 2
Serious events: 8 serious events
Other events: 163 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo Group
n=194 participants at risk
|
Galantamine Group 1
n=192 participants at risk
Galantamine 16 mg/day
|
Galantamine Group 2
n=194 participants at risk
Galantamine 24 mg/day
|
|---|---|---|---|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/194 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/194 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/194 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
1.0%
2/194 • Number of events 2 • Approximately 28 weeks
|
|
Infections and infestations
Pneumonia
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
|
Infections and infestations
Bronchitis
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Infections and infestations
Pyelonephritis acute
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.00%
0/194 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.00%
0/194 • Approximately 28 weeks
|
0.52%
1/192 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.00%
0/194 • Approximately 28 weeks
|
0.52%
1/192 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric adenoma
|
0.00%
0/194 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
|
Blood and lymphatic system disorders
Anemia folate deficiency
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Metabolism and nutrition disorders
Anorexia
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
0.52%
1/192 • Number of events 1 • Approximately 28 weeks
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/194 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
|
Nervous system disorders
Dementia Alzheimer's type
|
0.00%
0/194 • Approximately 28 weeks
|
0.52%
1/192 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Nervous system disorders
Post-traumatic headache
|
0.00%
0/194 • Approximately 28 weeks
|
0.52%
1/192 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Nervous system disorders
Cerebral infarction
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Nervous system disorders
Haemorrhagic cerebral infarction
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Nervous system disorders
Syncope
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Cardiac disorders
Bradycardia
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Respiration failure
|
0.00%
0/194 • Approximately 28 weeks
|
0.52%
1/192 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Haemothorax
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Hepatobiliary disorders
Bile duct stone
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Skin and subcutaneous tissue disorders
Subcutaneous emphysema
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/194 • Approximately 28 weeks
|
0.52%
1/192 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Investigations
Weight decreased
|
0.00%
0/194 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
|
Injury, poisoning and procedural complications
Compression fracture
|
0.00%
0/194 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/194 • Approximately 28 weeks
|
0.52%
1/192 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/194 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/194 • Approximately 28 weeks
|
0.52%
1/192 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
1.0%
2/194 • Number of events 2 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.52%
1/194 • Number of events 1 • Approximately 28 weeks
|
0.00%
0/192 • Approximately 28 weeks
|
0.00%
0/194 • Approximately 28 weeks
|
Other adverse events
| Measure |
Placebo Group
n=194 participants at risk
|
Galantamine Group 1
n=192 participants at risk
Galantamine 16 mg/day
|
Galantamine Group 2
n=194 participants at risk
Galantamine 24 mg/day
|
|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
18.6%
36/194 • Number of events 57 • Approximately 28 weeks
|
20.8%
40/192 • Number of events 53 • Approximately 28 weeks
|
19.6%
38/194 • Number of events 51 • Approximately 28 weeks
|
|
Metabolism and nutrition disorders
Anorexia
|
4.6%
9/194 • Number of events 12 • Approximately 28 weeks
|
9.4%
18/192 • Number of events 28 • Approximately 28 weeks
|
8.2%
16/194 • Number of events 20 • Approximately 28 weeks
|
|
Metabolism and nutrition disorders
Decreased appetite
|
4.1%
8/194 • Number of events 11 • Approximately 28 weeks
|
5.2%
10/192 • Number of events 12 • Approximately 28 weeks
|
7.2%
14/194 • Number of events 18 • Approximately 28 weeks
|
|
Nervous system disorders
Headache
|
8.8%
17/194 • Number of events 24 • Approximately 28 weeks
|
4.7%
9/192 • Number of events 10 • Approximately 28 weeks
|
5.7%
11/194 • Number of events 18 • Approximately 28 weeks
|
|
Gastrointestinal disorders
Nausea
|
5.7%
11/194 • Number of events 15 • Approximately 28 weeks
|
12.5%
24/192 • Number of events 44 • Approximately 28 weeks
|
16.5%
32/194 • Number of events 61 • Approximately 28 weeks
|
|
Gastrointestinal disorders
Vomiting
|
8.2%
16/194 • Number of events 20 • Approximately 28 weeks
|
13.5%
26/192 • Number of events 38 • Approximately 28 weeks
|
10.8%
21/194 • Number of events 44 • Approximately 28 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
9.3%
18/194 • Number of events 23 • Approximately 28 weeks
|
9.9%
19/192 • Number of events 43 • Approximately 28 weeks
|
10.8%
21/194 • Number of events 31 • Approximately 28 weeks
|
|
Gastrointestinal disorders
Constipation
|
2.1%
4/194 • Number of events 4 • Approximately 28 weeks
|
6.2%
12/192 • Number of events 13 • Approximately 28 weeks
|
3.1%
6/194 • Number of events 6 • Approximately 28 weeks
|
|
Investigations
Weight decreased
|
2.6%
5/194 • Number of events 5 • Approximately 28 weeks
|
6.2%
12/192 • Number of events 12 • Approximately 28 weeks
|
5.2%
10/194 • Number of events 10 • Approximately 28 weeks
|
|
Investigations
Blood creatine phosphokinase increased
|
2.1%
4/194 • Number of events 4 • Approximately 28 weeks
|
5.2%
10/192 • Number of events 10 • Approximately 28 weeks
|
5.2%
10/194 • Number of events 11 • Approximately 28 weeks
|
|
Injury, poisoning and procedural complications
Fall
|
11.3%
22/194 • Number of events 28 • Approximately 28 weeks
|
11.5%
22/192 • Number of events 31 • Approximately 28 weeks
|
7.7%
15/194 • Number of events 18 • Approximately 28 weeks
|
|
Injury, poisoning and procedural complications
Contusion
|
5.2%
10/194 • Number of events 11 • Approximately 28 weeks
|
5.2%
10/192 • Number of events 11 • Approximately 28 weeks
|
6.2%
12/194 • Number of events 12 • Approximately 28 weeks
|
Additional Information
Director
Janssen Pharm KK Japan
Phone: 81-3-4411-5717
Results disclosure agreements
- Principal investigator is a sponsor employee The disclosure restriction on PI is that the sponsor can review results communications prior to public release and can embargo communications regarding results for a period as the sponsor requires.
- Publication restrictions are in place
Restriction type: OTHER