An Efficacy and Safety Study of Galantamine for the Treatment of Patients With Alzheimer's Disease - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver); Primary Purpose: Treatment
Condition:	Alzheimer's Disease
Interventions:	Drug: Placebo Drug: Galantamine 16 mg/day Drug: Galantamine 24 mg/day

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Placebo Group	No text entered.
Galantamine Group 1	Galantamine 16 mg/day
Galantamine Group 2	Galantamine 24 mg/day

Participant Flow: Overall Study

	Placebo Group	Galantamine Group 1	Galantamine Group 2
STARTED	194	192	194
COMPLETED	160	154	151
NOT COMPLETED	34	38	43
Adverse Event	15	16	19
Withdrawal by Subject	9	11	14
Inappropriate as a subject	1	1	1
Change of patients for CIBIC plus-J	1	1	0
Missing or change of caregiver	6	2	4
Non-compliance	0	1	1
Not specified	2	6	4

Baseline Characteristics

Hide Baseline Characteristics

Reporting Groups

	Description
Placebo Group	No text entered.
Galantamine Group 1	Galantamine 16 mg/day
Galantamine Group 2	Galantamine 24 mg/day
Total	Total of all reporting groups

Baseline Measures

	Placebo Group	Galantamine Group 1	Galantamine Group 2	Total
Number of Participants [units: participants]	191	191	192	574
Age ^[1] [units: years] Mean ± Standard Deviation	75.5 ± 7.6	75.6 ± 8.4	74.6 ± 8.8	75.2 ± 8.3
Gender ^[2] [units: participants]
Female	132	125	145	402
Male	59	66	47	172

[1]	Six participants were excluded from the randomized patients as no evaluation on both ADAS and CIBIC was made after treatment with study medication.
[2]	Six participants were excluded from the randomized patients as no evaluation on both Alzheimer's disease assessment scale (ADAS) and Clinician's Interview-Based Impression of Change (CIBIC) was made after treatment with study medication.

Outcome Measures

Hide All Outcome Measures

1. Primary:

Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog) [ Time Frame: Baseline and 24 weeks ]

Measure Type	Primary
Measure Title	Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog)
Measure Description	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.
Time Frame	Baseline and 24 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population. Last observation carried forward (LOCF) end point.

Reporting Groups

	Description
Placebo Group	No text entered.
Galantamine Group 1	Galantamine 16 mg/day
Galantamine Group 2	Galantamine 24 mg/day

Measured Values

	Placebo Group	Galantamine Group 1	Galantamine Group 2
Number of Participants Analyzed [units: participants]	191	191	192
Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog) [units: Scores on a scale] Mean ± Standard Deviation	0.90 ± 5.89	-0.58 ± 5.87	-1.66 ± 5.37

Statistical Analysis 1 for Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog)

Groups ^[1]	Placebo Group vs. Galantamine Group 1
Method ^[2]	Least Square Means
P Value ^[3]	0.0113
Mean Difference (Final Values) ^[4]	-1.49
95% Confidence Interval	( -2.64 to -0.34 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog)

Groups ^[1]	Placebo Group vs. Galantamine Group 2
Method ^[2]	Least Square Means
P Value ^[3]	<0.0001
Mean Difference (Final Values) ^[4]	-2.59
95% Confidence Interval	( -3.74 to -1.44 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

2. Primary:

Distribution of Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) [ Time Frame: 24 weeks ]

Measure Type	Primary
Measure Title	Distribution of Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J)
Measure Description	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”.
Time Frame	24 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population. Last observation carried forward (LOCF) end point.

Reporting Groups

	Description
Placebo Group	No text entered.
Galantamine Group 1	Galantamine 16 mg/day
Galantamine Group 2	Galantamine 24 mg/day

Measured Values

	Placebo Group	Galantamine Group 1	Galantamine Group 2
Number of Participants Analyzed [units: participants]	191	191	192
Distribution of Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) [units: patients]
Markedly improved	0	0	1
Moderately improved	7	12	4
Minimally improved	36	39	32
No change	64	60	73
Minimally worse	62	64	61
Moderately worse	22	16	20
Markedly worse	0	0	1

No statistical analysis provided for Distribution of Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J)

3. Secondary:

Change From Baseline in the Disability Assessment for Dementia (DAD) [ Time Frame: Baseline and 24 weeks ]

Measure Type	Secondary
Measure Title	Change From Baseline in the Disability Assessment for Dementia (DAD)
Measure Description	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.
Time Frame	Baseline and 24 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population. Last observation carried forward (LOCF) end point.

Reporting Groups

	Description
Placebo Group	No text entered.
Galantamine Group 1	Galantamine 16 mg/day
Galantamine Group 2	Galantamine 24 mg/day

Measured Values

	Placebo Group	Galantamine Group 1	Galantamine Group 2
Number of Participants Analyzed [units: participants]	191	191	192
Change From Baseline in the Disability Assessment for Dementia (DAD) [units: Scores on a scale] Mean ± Standard Deviation	-2.8 ± 10.3	-1.0 ± 9.4	-2.2 ± 9.3

Statistical Analysis 1 for Change From Baseline in the Disability Assessment for Dementia (DAD)

Groups ^[1]	Placebo Group vs. Galantamine Group 1
Method ^[2]	Least Square Means
P Value ^[3]	0.0774
Mean Difference (Final Values) ^[4]	1.8
95% Confidence Interval	( -0.2 to 3.7 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change From Baseline in the Disability Assessment for Dementia (DAD)

Groups ^[1]	Placebo Group vs. Galantamine Group 2
Method ^[2]	Least Square Means
P Value ^[3]	0.6207
Mean Difference (Final Values) ^[4]	0.5
95% Confidence Interval	( -1.5 to 2.4 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

4. Secondary:

Change From Baseline in the Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) [ Time Frame: Baseline and 24 weeks ]

Measure Type	Secondary
Measure Title	Change From Baseline in the Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD)
Measure Description	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).
Time Frame	Baseline and 24 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population. Last observation carried forward (LOCF) end point.

Reporting Groups

	Description
Placebo Group	No text entered.
Galantamine Group 1	Galantamine 16 mg/day
Galantamine Group 2	Galantamine 24 mg/day

Measured Values

	Placebo Group	Galantamine Group 1	Galantamine Group 2
Number of Participants Analyzed [units: participants]	191	191	192
Change From Baseline in the Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) [units: Scores on a scale] Mean ± Standard Deviation	0.0 ± 3.1	-0.2 ± 4.2	-0.3 ± 3.1

Statistical Analysis 1 for Change From Baseline in the Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD)

Groups ^[1]	Placebo Group vs. Galantamine Group 1
Method ^[2]	Least Square Means
P Value ^[3]	0.8419
Mean Difference (Final Values) ^[4]	0.1
95% Confidence Interval	( -0.6 to 0.8 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change From Baseline in the Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD)

Groups ^[1]	Placebo Group vs. Galantamine Group 2
Method ^[2]	Least Square Means
P Value ^[3]	0.7942
Mean Difference (Final Values) ^[4]	-0.1
95% Confidence Interval	( -0.8 to 0.6 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

5. Secondary:

Change From Baseline in the Mental Function Impairment Scale (MENFIS) [ Time Frame: Baseline and 24 weeks ]

Measure Type	Secondary
Measure Title	Change From Baseline in the Mental Function Impairment Scale (MENFIS)
Measure Description	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).
Time Frame	Baseline and 24 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population. Last observation carried forward (LOCF) end point.

Reporting Groups

	Description
Placebo Group	No text entered.
Galantamine Group 1	Galantamine 16 mg/day
Galantamine Group 2	Galantamine 24 mg/day

Measured Values

	Placebo Group	Galantamine Group 1	Galantamine Group 2
Number of Participants Analyzed [units: participants]	191	191	192
Change From Baseline in the Mental Function Impairment Scale (MENFIS) [units: Scores on a scale] Mean ± Standard Deviation	2.2 ± 5.2	1.6 ± 5.2	1.9 ± 5.2

Statistical Analysis 1 for Change From Baseline in the Mental Function Impairment Scale (MENFIS)

Groups ^[1]	Placebo Group vs. Galantamine Group 1
Method ^[2]	Least Square Means
P Value ^[3]	0.3141
Mean Difference (Final Values) ^[4]	-0.5
95% Confidence Interval	( -1.6 to 0.5 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change From Baseline in the Mental Function Impairment Scale (MENFIS)

Groups ^[1]	Placebo Group vs. Galantamine Group 2
Method ^[2]	Least Square Means
P Value ^[3]	0.6089
Mean Difference (Final Values) ^[4]	-0.3
95% Confidence Interval	( -1.3 to 0.8 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Serious Adverse Events

Show Serious Adverse Events

Other Adverse Events

Show Other Adverse Events

More Information

Hide More Information

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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Director
Organization: Janssen Pharm KK Japan
phone: 81-3-4411-5717

No publications provided

Responsible Party:	Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier:	NCT00814801 History of Changes
Other Study ID Numbers:	CR010297, GAL-JPN-5
Study First Received:	December 24, 2008
Results First Received:	March 13, 2012
Last Updated:	April 25, 2013
Health Authority:	Japan: Japan Pharmaceuticals And Medical Devices Evaluation Center