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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
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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
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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
  Show All Outcome Measures

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

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

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

4.  Secondary:   Change From Baseline in Disability Assessment in Dementia (DAD) Scores   [ Time Frame: Baseline, Month 24 ]

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 ]

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 ]

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

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 ]
  Hide Outcome Measure 9

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: ScoresĀ onĀ 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
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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
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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:
unchecked 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.
unchecked 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.


Results Point of Contact:  
Name/Title: Director, Clinical Research
Organization: Johnson & Johnson Pharmaceutical Research & Development
phone: 1 609-730-7674


No publications provided


Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT00679627     History of Changes
Other Study ID Numbers: CR012463, GALALZ3005
Study First Received: May 15, 2008
Results First Received: April 23, 2013
Last Updated: September 10, 2013
Health Authority: Germany: Ethics Commission
Greece: National Organization of Medicines
Austria: Ethikkommission
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency
Slovakia: State Institute for Drug Control
Slovenia: Agency for Medicinal Products - Ministry of Health
Spain: Comité Ético de Investigación Clínica
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee
Austria: Agency for Health and Food Safety
Germany: Federal Institute for Drugs and Medical Devices
France: Institutional Ethical Committee
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Estonia: The State Agency of Medicine
Czech Republic: State Institute for Drug Control
Italy: Ethics Committee
Ukraine: State Pharmacological Center - Ministry of Health