A Study of Galantamine Used to Treat Patients With Mild to Moderate Alzheimer's Disease

This study has been terminated.
(Due to a pre-specified imbalance of deaths between treatment groups, the DSMB recommended early termination of the trial)
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT00679627
First received: May 15, 2008
Last updated: September 10, 2013
Last verified: September 2013
Results First Received: April 23, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Alzheimer's Disease
Interventions: Drug: Galantamine
Drug: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study investigated the benefits and risks of long-term galantamine use in participants with Alzheimer's Disease. The study was conducted from 19 May 2008 to 20 May 2012 at 127 clinical centers in 13 countries. A total of 2051 participants were randomized to study treatment, of these 2045 received at least 1 dose of treatment.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The Data Safety Monitoring Board (DSMB) recommended that the study be terminated early because of an imbalance of deaths between the treatment groups.

Reporting Groups
  Description
Placebo During the titration and long-term maintenance periods, placebo was supplied as oral capsules matching galantamine capsules in size and appearance. The study drug was administered using the same titration and maintenance regimens as was used for participants in the galantamine treatment group.
Galantamine During the titration period (Days 1 to 84), participants received galantamine controlled-release oral capsules 8 mg/day for the first 4 weeks, followed by 16 mg/day for the next 4 weeks, then 24 mg/day for the next 4 weeks (based on tolerability). During the long-term maintenance period (Months 4 to 24), participants received galantamine at the dosage achieved at Day 84 of the titration period and continued until the completion of the Month 24 visit. A one-time dose titration to 16 or 24 mg/day was allowed, based on the investigator’s judgment and participant tolerability.

Participant Flow:   Overall Study
    Placebo     Galantamine  
STARTED     1021     1024  
COMPLETED     322     339  
NOT COMPLETED     699     685  
Death                 41                 29  
Adverse Event                 43                 53  
Withdrawal by Subject                 168                 172  
Lost to Follow-up                 22                 26  
Early Study Closure                 425                 405  



  Baseline Characteristics
  Hide Baseline Characteristics

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.
No text entered.

Reporting Groups
  Description
Placebo During the titration and long-term maintenance periods, placebo was supplied as oral capsules matching galantamine capsules in size and appearance. The study drug was administered using the same titration and maintenance regimens as was used for participants in the galantamine treatment group.
Galantamine During the titration period (Days 1 to 84), participants received galantamine controlled-release oral capsules 8 mg/day for the first 4 weeks, followed by 16 mg/day for the next 4 weeks, then 24 mg/day for the next 4 weeks (based on tolerability). During the long-term maintenance period (Months 4 to 24), participants received galantamine at the dosage achieved at Day 84 of the titration period and continued until the completion of the Month 24 visit. A one-time dose titration to 16 or 24 mg/day was allowed, based on the investigator’s judgment and participant tolerability.
Total Total of all reporting groups

Baseline Measures
    Placebo     Galantamine     Total  
Number of Participants  
[units: participants]
  1021     1024     2045  
Age  
[units: participants]
Mean ± Standard Deviation
  73.2  ± 8.67     73  ± 8.88     73.1  ± 8.77  
Age, Customized  
[units: participants]
     
<61     112     112     224  
61-<76     467     466     933  
>=76     442     446     888  
Gender  
[units: participants]
     
Female     654     671     1325  
Male     367     353     720  
Region of Enrollment  
[units: participants]
     
Czech Republic     33     34     67  
Estonia     53     51     104  
France     10     11     21  
Germany     218     221     439  
Greece     35     36     71  
Italy     25     24     49  
Latvia     2     2     4  
Lithuania     23     21     44  
Romania     84     84     168  
Russia     274     271     545  
Slovakia     85     88     173  
Slovenia     13     13     26  
Ukraine     166     168     334  



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Change From Baseline in the Mini–Mental State Examination (MMSE) Score   [ Time Frame: Baseline, Month 24 ]

Measure Type Primary
Measure Title Change From Baseline in the Mini–Mental State Examination (MMSE) Score
Measure Description The MMSE is a brief 30-point questionnaire test that is used or the assessment of dementia patients’ cognitive impairment. Evaluation of points are as follows: 24 to 30 = no cognitive impairment, 18 to 23 = mild cognitive impairment, 0 to 17 = severe cognitive impairment. Lower scores indicate worsening.
Time Frame Baseline, Month 24  
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.
An intent-to-treat (ITT) with last observation carried forward (LOCF) approach was used for the primary analysis. The ITT analysis set included all randomized participants who received at least 1 dose of treatment and had at least 1 postbaseline MMSE measure.

Reporting Groups
  Description
Placebo During the titration and long-term maintenance periods, placebo was supplied as oral capsules matching galantamine capsules in size and appearance. The study drug was administered using the same titration and maintenance regimens as was used for participants in the galantamine treatment group.
Galantamine During the titration period (Days 1 to 84), participants received galantamine controlled-release oral capsules 8 mg/day for the first 4 weeks, followed by 16 mg/day for the next 4 weeks, then 24 mg/day for the next 4 weeks (based on tolerability). During the long-term maintenance period (Months 4 to 24), participants received galantamine at the dosage achieved at Day 84 of the titration period and continued until the completion of the Month 24 visit. A one-time dose titration to 16 or 24 mg/day was allowed, based on the investigator’s judgment and participant tolerability.

Measured Values
    Placebo     Galantamine  
Number of Participants Analyzed  
[units: participants]
  906     906  
Change From Baseline in the Mini–Mental State Examination (MMSE) Score  
[units: Scores on scale]
Mean ± Standard Deviation
  -2.14  ± 4.340     -1.41  ± 4.050  


Statistical Analysis 1 for Change From Baseline in the Mini–Mental State Examination (MMSE) Score
Groups [1] All groups
Method [2] ANCOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method 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.



2.  Primary:   The Number of Deaths Reported in Participants   [ Time Frame: Up to 2 years ]

Measure Type Primary
Measure Title The Number of Deaths Reported in Participants
Measure Description An external Data Safety Monitoring Board (DSMB) was assigned for this study to monitor the progress of the study and to ensure that the safety of participants was not compromised.
Time Frame Up to 2 years  
Safety Issue Yes  

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.
The safety analysis was performed on the safety population, ie, all randomized participants who received at least one dose of the study drug.

Reporting Groups
  Description
Placebo During the titration and long-term maintenance periods, placebo was supplied as oral capsules matching galantamine capsules in size and appearance. The study drug was administered using the same titration and maintenance regimens as was used for participants in the galantamine treatment group.
Galantamine During the titration period (Days 1 to 84), participants received galantamine controlled-release oral capsules 8 mg/day for the first 4 weeks, followed by 16 mg/day for the next 4 weeks, then 24 mg/day for the next 4 weeks (based on tolerability). During the long-term maintenance period (Months 4 to 24), participants received galantamine at the dosage achieved at Day 84 of the titration period and continued until the completion of the Month 24 visit. A one-time dose titration to 16 or 24 mg/day was allowed, based on the investigator’s judgment and participant tolerability.

Measured Values
    Placebo     Galantamine  
Number of Participants Analyzed  
[units: participants]
  1021     1024  
The Number of Deaths Reported in Participants  
[units: Number of Participants]
  56     33  


Statistical Analysis 1 for The Number of Deaths Reported in Participants
Groups [1] All groups
Method [2] Regression, Cox
P Value [3] 0.011
Hazard Ratio (HR) [4] 0.58
95% Confidence Interval ( 0.37 to 0.89 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method 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.



3.  Secondary:   Change From Baseline in the Mini–Mental State Examination (MMSE) Score   [ Time Frame: Baseline, Month 6 ]

Measure Type Secondary
Measure Title Change From Baseline in the Mini–Mental State Examination (MMSE) Score
Measure Description The MMSE is a brief 30-point questionnaire test that is used or the assessment of dementia patients’ cognitive impairment. Evaluation of points are as follows: 24 to 30 = no cognitive impairment, 18 to 23 = mild cognitive impairment, 0 to 17 = severe cognitive impairment. Lower scores indicate worsening.
Time Frame Baseline, Month 6  
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.
An intent-to-treat (ITT) with last observation carried forward (LOCF) approach was used for the primary analysis. The ITT analysis set included all randomized participants who received at least 1 dose of treatment and had at least 1 postbaseline MMSE measure.

Reporting Groups
  Description
Placebo During the titration and long-term maintenance periods, placebo was supplied as oral capsules matching galantamine capsules in size and appearance. The study drug was administered using the same titration and maintenance regimens as was used for participants in the galantamine treatment group.
Galantamine During the titration period (Days 1 to 84), participants received galantamine controlled-release oral capsules 8 mg/day for the first 4 weeks, followed by 16 mg/day for the next 4 weeks, then 24 mg/day for the next 4 weeks (based on tolerability). During the long-term maintenance period (Months 4 to 24), participants received galantamine at the dosage achieved at Day 84 of the titration period and continued until the completion of the Month 24 visit. A one-time dose titration to 16 or 24 mg/day was allowed, based on the investigator’s judgment and participant tolerability.

Measured Values
    Placebo     Galantamine  
Number of Participants Analyzed  
[units: participants]
  906     906  
Change From Baseline in the Mini–Mental State Examination (MMSE) Score  
[units: Scores on scale]
Mean ± Standard Deviation
  -0.28  ± 2.938     0.15  ± 2.725  


Statistical Analysis 1 for Change From Baseline in the Mini–Mental State Examination (MMSE) Score
Groups [1] All groups
Method [2] ANCOVA
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method 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.  Secondary:   Change From Baseline in Disability Assessment in Dementia (DAD) Scores   [ Time Frame: Baseline, Month 24 ]

Measure Type Secondary
Measure Title Change From Baseline in Disability Assessment in Dementia (DAD) Scores
Measure Description The DAD assesses physical activities of daily living and instrumental-activities of daily livings of participants with Alzheimer disease. This measure is a validated, disability assessment scale that collects information regarding the ability of a participant to initiate, plan, organize, and perform activities of daily living, as based on a structured interview with the caregiver. The maximum scores were 13 for initiation, 10 for planning and organizing, and 17 for effective performance in order to yield a total maximum score of 40. These scores were normalized to a scale of 100 for analysis.A higher score, or percentage of items that can be performed represents fewer disabilities in carrying out activities of daily living while a lower percentage indicates an increase in disabilities.
Time Frame Baseline, Month 24  
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.
An intent-to-treat (ITT) with last observation carried forward (LOCF) approach was used for the analysis. The ITT analysis set included all randomized participants who received at least 1 dose of treatment and had at least 1 postbaseline DAD measure.

Reporting Groups
  Description
Placebo During the titration and long-term maintenance periods, placebo was supplied as oral capsules matching galantamine capsules in size and appearance. The study drug was administered using the same titration and maintenance regimens as was used for participants in the galantamine treatment group.
Galantamine During the titration period (Days 1 to 84), participants received galantamine controlled-release oral capsules 8 mg/day for the first 4 weeks, followed by 16 mg/day for the next 4 weeks, then 24 mg/day for the next 4 weeks (based on tolerability). During the long-term maintenance period (Months 4 to 24), participants received galantamine at the dosage achieved at Day 84 of the titration period and continued until the completion of the Month 24 visit. A one-time dose titration to 16 or 24 mg/day was allowed, based on the investigator’s judgment and participant tolerability.

Measured Values
    Placebo     Galantamine  
Number of Participants Analyzed  
[units: participants]
  906     906  
Change From Baseline in Disability Assessment in Dementia (DAD) Scores  
[units: Scores on scale]
Mean ± Standard Deviation
  -10.81  ± 18.268     -8.16  ± 17.251  


Statistical Analysis 1 for Change From Baseline in Disability Assessment in Dementia (DAD) Scores
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.002
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method 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.



5.  Secondary:   Change From Baseline in Patient Accommodation Measured Using the Assessment of Subject Accommodation Status and Caregiver Burden (APAS-CarB)   [ Time Frame: Baseline, Months 12 and 24 ]

Measure Type Secondary
Measure Title Change From Baseline in Patient Accommodation Measured Using the Assessment of Subject Accommodation Status and Caregiver Burden (APAS-CarB)
Measure Description The APAS-CarB is a measure used to evaluate participant status and caregiver burden. The table below presents Patient Accommodation assessed as the percentage of participants “home with friend or relative” using the APAS-CarB.
Time Frame Baseline, Months 12 and 24  
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.
An intent-to-treat (ITT) with last observation carried forward (LOCF) approach was used for the analysis. The ITT analysis set included all randomized participants who received at least 1 dose of treatment and had at least 1 postbaseline APAS-CarB measure.

Reporting Groups
  Description
Placebo During the titration and long-term maintenance periods, placebo was supplied as oral capsules matching galantamine capsules in size and appearance. The study drug was administered using the same titration and maintenance regimens as was used for participants in the galantamine treatment group.
Galantamine During the titration period (Days 1 to 84), participants received galantamine controlled-release oral capsules 8 mg/day for the first 4 weeks, followed by 16 mg/day for the next 4 weeks, then 24 mg/day for the next 4 weeks (based on tolerability). During the long-term maintenance period (Months 4 to 24), participants received galantamine at the dosage achieved at Day 84 of the titration period and continued until the completion of the Month 24 visit. A one-time dose titration to 16 or 24 mg/day was allowed, based on the investigator’s judgment and participant tolerability.

Measured Values
    Placebo     Galantamine  
Number of Participants Analyzed  
[units: participants]
  906     906  
Change From Baseline in Patient Accommodation Measured Using the Assessment of Subject Accommodation Status and Caregiver Burden (APAS-CarB)  
[units: Percentage of participants]
   
Home with friend or relative - Baseline     62.1     62.8  
Home with friend or relative - Month 12     61.4     61.8  
Home with friend or relative - Month 24     55.3     60.1  

No statistical analysis provided for Change From Baseline in Patient Accommodation Measured Using the Assessment of Subject Accommodation Status and Caregiver Burden (APAS-CarB)



6.  Secondary:   Change From Baseline in Caregiver Time Spent With the Patient Measured Using the Assessment of Subject Accommodation Status and Caregiver Burden (APAS-CarB)   [ Time Frame: Baseline, Months 12 and 24 ]

Measure Type Secondary
Measure Title Change From Baseline in Caregiver Time Spent With the Patient Measured Using the Assessment of Subject Accommodation Status and Caregiver Burden (APAS-CarB)
Measure Description The table below presents the number of days that caregiving activities were provided during the past week.
Time Frame Baseline, Months 12 and 24  
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.
The ITT analysis set included all randomized participants who received at least 1 dose of treatment and had at least 1 postbaseline measure.

Reporting Groups
  Description
Placebo During the titration and long-term maintenance periods, placebo was supplied as oral capsules matching galantamine capsules in size and appearance. The study drug was administered using the same titration and maintenance regimens as was used for participants in the galantamine treatment group.
Galantamine During the titration period (Days 1 to 84), participants received galantamine controlled-release oral capsules 8 mg/day for the first 4 weeks, followed by 16 mg/day for the next 4 weeks, then 24 mg/day for the next 4 weeks (based on tolerability). During the long-term maintenance period (Months 4 to 24), participants received galantamine at the dosage achieved at Day 84 of the titration period and continued until the completion of the Month 24 visit. A one-time dose titration to 16 or 24 mg/day was allowed, based on the investigator’s judgment and participant tolerability.

Measured Values
    Placebo     Galantamine  
Number of Participants Analyzed  
[units: participants]
  906     906  
Change From Baseline in Caregiver Time Spent With the Patient Measured Using the Assessment of Subject Accommodation Status and Caregiver Burden (APAS-CarB)  
[units: Days]
Mean ± Standard Deviation
   
Provided caregiving during past week - Baseline     5.91  ± 2.094     5.77  ± 2.241  
Provided caregiving during past week - Month 12     6.06  ± 1.964     6.07  ± 1.969  
Provided caregiving during past week - Month 24     6.13  ± 1.952     6.20  ± 1.830  

No statistical analysis provided for Change From Baseline in Caregiver Time Spent With the Patient Measured Using the Assessment of Subject Accommodation Status and Caregiver Burden (APAS-CarB)



7.  Secondary:   Change From Baseline in Institutional Status   [ Time Frame: Baseline, Month 24 ]

Measure Type Secondary
Measure Title Change From Baseline in Institutional Status
Measure Description This table describes the number of participants who were reported as institutionalized at baseline and Month 24.
Time Frame Baseline, Month 24  
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.
The ITT analysis set included all randomized participants who received at least 1 dose of treatment and had at least 1 postbaseline measure.

Reporting Groups
  Description
Placebo During the titration and long-term maintenance periods, placebo was supplied as oral capsules matching galantamine capsules in size and appearance. The study drug was administered using the same titration and maintenance regimens as was used for participants in the galantamine treatment group.
Galantamine During the titration period (Days 1 to 84), participants received galantamine controlled-release oral capsules 8 mg/day for the first 4 weeks, followed by 16 mg/day for the next 4 weeks, then 24 mg/day for the next 4 weeks (based on tolerability). During the long-term maintenance period (Months 4 to 24), participants received galantamine at the dosage achieved at Day 84 of the titration period and continued until the completion of the Month 24 visit. A one-time dose titration to 16 or 24 mg/day was allowed, based on the investigator’s judgment and participant tolerability.

Measured Values
    Placebo     Galantamine  
Number of Participants Analyzed  
[units: participants]
  906     906  
Change From Baseline in Institutional Status  
[units: Number of Participants]
   
Baseline     1     0  
Month 24     5     6  


Statistical Analysis 1 for Change From Baseline in Institutional Status
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.269
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method 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:
  Baseline

Statistical Analysis 2 for Change From Baseline in Institutional Status
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.835
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method 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:
  Month 24



8.  Secondary:   Change From Baseline in the Mini–Mental State Examination (MMSE) Subscales (Orientation, Registration, Attention and Calculation, Recall, and Language)   [ Time Frame: Baseline, Month 24 ]

Measure Type Secondary
Measure Title Change From Baseline in the Mini–Mental State Examination (MMSE) Subscales (Orientation, Registration, Attention and Calculation, Recall, and Language)
Measure Description The MMSE, is a validated, brief examination that rates subjects on orientation (total score, 10), registration (total score, 3), attention (total score, 5), calculation (total score, 5), recall (total score, 3), and language (total score, 9). The maximum score is 30 (only the higher of the two scores for attention and calculation [each with a maximum score of 5] was used). A higher score compared with baseline indicates less impairment.
Time Frame Baseline, Month 24  
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.
The ITT analysis set included all randomized participants who received at least 1 dose of treatment and had at least 1 postbaseline MMSE measure.

Reporting Groups
  Description
Placebo During the titration and long-term maintenance periods, placebo was supplied as oral capsules matching galantamine capsules in size and appearance. The study drug was administered using the same titration and maintenance regimens as was used for participants in the galantamine treatment group.
Galantamine During the titration period (Days 1 to 84), participants received galantamine controlled-release oral capsules 8 mg/day for the first 4 weeks, followed by 16 mg/day for the next 4 weeks, then 24 mg/day for the next 4 weeks (based on tolerability). During the long-term maintenance period (Months 4 to 24), participants received galantamine at the dosage achieved at Day 84 of the titration period and continued until the completion of the Month 24 visit. A one-time dose titration to 16 or 24 mg/day was allowed, based on the investigator’s judgment and participant tolerability.

Measured Values
    Placebo     Galantamine  
Number of Participants Analyzed  
[units: participants]
  906     906  
Change From Baseline in the Mini–Mental State Examination (MMSE) Subscales (Orientation, Registration, Attention and Calculation, Recall, and Language)  
[units: Scores on scale]
Mean ± Standard Deviation
   
Orientation     -0.96  ± 2.320     -0.76  ± 2.128  
Registration     -0.20  ± 0.771     -0.16  ± 0.692  
Attention and Calculation     -0.46  ± 1.526     -0.16  ± 1.561  
Recall     0.00  ± 1.013     0.10  ± 1.070  
Language     -0.93  ± 1.895     -0.68  ± 1.867  


Statistical Analysis 1 for Change From Baseline in the Mini–Mental State Examination (MMSE) Subscales (Orientation, Registration, Attention and Calculation, Recall, and Language)
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.194
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method 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:
  Orientation subscale

Statistical Analysis 2 for Change From Baseline in the Mini–Mental State Examination (MMSE) Subscales (Orientation, Registration, Attention and Calculation, Recall, and Language)
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.353
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method 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:
  Registration subscale

Statistical Analysis 3 for Change From Baseline in the Mini–Mental State Examination (MMSE) Subscales (Orientation, Registration, Attention and Calculation, Recall, and Language)
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.009
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method 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:
  Attention and Calculation subscale

Statistical Analysis 4 for Change From Baseline in the Mini–Mental State Examination (MMSE) Subscales (Orientation, Registration, Attention and Calculation, Recall, and Language)
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.158
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method 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:
  Recall subscale

Statistical Analysis 5 for Change From Baseline in the Mini–Mental State Examination (MMSE) Subscales (Orientation, Registration, Attention and Calculation, Recall, and Language)
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.088
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method 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:
  Language subscale



9.  Secondary:   Change From Baseline in the Disability Assessment in Dementia (DAD) Subscales (Initiation, Planning and Organization, Effective Performance, Basic, Instrumental, and Leisure)   [ Time Frame: Baseline, Month 24 ]

Measure Type Secondary
Measure Title Change From Baseline in the Disability Assessment in Dementia (DAD) Subscales (Initiation, Planning and Organization, Effective Performance, Basic, Instrumental, and Leisure)
Measure Description The DAD assesses physical activities of daily living and instrumental-activities of daily livings of participants with Alzheimer disease. This measure is a validated, disability assessment scale that collects information regarding the ability of a participant to initiate, plan, organize, and perform activities of daily living, as based on a structured interview with the caregiver. The maximum scores were 13 for initiation, 10 for planning and organizing, and 17 for effective performance in order to yield a total maximum score of 40. These scores were normalized to a scale of 100 for analysis.A higher score, or percentage of items that can be performed represents fewer disabilities in carrying out activities of daily living while a lower percentage indicates an increase in disabilities.
Time Frame Baseline, Month 24  
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.
This analysis was performed in the intent-to-treat population which included all randomized participants who had at least 1 postbaseline DAD measure.

Reporting Groups
  Description
Placebo During the titration and long-term maintenance periods, placebo was supplied as oral capsules matching galantamine capsules in size and appearance. The study drug was administered using the same titration and maintenance regimens as was used for participants in the galantamine treatment group.
Galantamine During the titration period (Days 1 to 84), participants received galantamine controlled-release oral capsules 8 mg/day for the first 4 weeks, followed by 16 mg/day for the next 4 weeks, then 24 mg/day for the next 4 weeks (based on tolerability). During the long-term maintenance period (Months 4 to 24), participants received galantamine at the dosage achieved at Day 84 of the titration period and continued until the completion of the Month 24 visit. A one-time dose titration to 16 or 24 mg/day was allowed, based on the investigator’s judgment and participant tolerability.

Measured Values
    Placebo     Galantamine  
Number of Participants Analyzed  
[units: participants]
  906     906  
Change From Baseline in the Disability Assessment in Dementia (DAD) Subscales (Initiation, Planning and Organization, Effective Performance, Basic, Instrumental, and Leisure)  
[units: Scores on scale]
Mean ± Standard Deviation
   
Initiation     -13.53  ± 22.993     -9.60  ± 20.660  
Planning and Organization     -13.14  ± 24.565     -9.96  ± 23.154  
Effective Performance     -13.82  ± 21.975     -10.82  ± 19.959  
Basic     -14.24  ± 24.093     -9.84  ± 21.899  
Instrumental     -13.52  ± 23.210     -10.72  ± 21.714  
Leisure     -13.02  ± 35.370     -10.46  ± 32.769  


Statistical Analysis 1 for Change From Baseline in the Disability Assessment in Dementia (DAD) Subscales (Initiation, Planning and Organization, Effective Performance, Basic, Instrumental, and Leisure)
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.010
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method 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:
  Initiation subscale

Statistical Analysis 2 for Change From Baseline in the Disability Assessment in Dementia (DAD) Subscales (Initiation, Planning and Organization, Effective Performance, Basic, Instrumental, and Leisure)
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.043
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method 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:
  Planning and Organization subscale

Statistical Analysis 3 for Change From Baseline in the Disability Assessment in Dementia (DAD) Subscales (Initiation, Planning and Organization, Effective Performance, Basic, Instrumental, and Leisure)
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.018
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method 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:
  Effective Performance subscale

Statistical Analysis 4 for Change From Baseline in the Disability Assessment in Dementia (DAD) Subscales (Initiation, Planning and Organization, Effective Performance, Basic, Instrumental, and Leisure)
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.005
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method 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:
  Basic subscale

Statistical Analysis 5 for Change From Baseline in the Disability Assessment in Dementia (DAD) Subscales (Initiation, Planning and Organization, Effective Performance, Basic, Instrumental, and Leisure)
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.054
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method 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:
  Instrumental subscale

Statistical Analysis 6 for Change From Baseline in the Disability Assessment in Dementia (DAD) Subscales (Initiation, Planning and Organization, Effective Performance, Basic, Instrumental, and Leisure)
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.137
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method 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:
  Leisure subscale




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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.


  More Information