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

History of Changes

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.
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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

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1. Primary:

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

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2. Primary:

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

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3. Secondary:

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

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4. Secondary:

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

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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 ]

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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 ]

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7. Secondary:

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

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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

Galantamine

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:
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[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 ]

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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 ]

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Serious Adverse Events

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Other Adverse Events

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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
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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:

	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: If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application.

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

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