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

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00679627
• Collaborator: (none)
• Enrollment: 2,051
• Locations: 102
• Arms: 2
• Duration (Months): 47
• Patients Per Site: 20.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the effectiveness and safety of 2 years of treatment with galantamine as compared with placebo of patients who have mild to moderately severe Alzheimer's disease (AD).

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: Galantamine; Drug: Placebo	Phase 3

Detailed Description

This is a long-term (2-year), randomized (patients will be assigned to treatment by chance), double blind (neither the physician nor the patient will know which treatment is assigned) study of galantamine versus placebo in subjects with mild to moderately-severe AD. Approximately 2,000 patients will participate in this study. The study length for each patient is approximately 25.5 months. The study consists of 3 phases: a pretreatment phase, a treatment phase, and a posttreatment phase. The pretreatment phase includes a 2-week screening period (to obtain a patient's and his or her caregiver's informed consent and to confirm eligibility for the study) and a baseline visit at which subjects will be randomly assigned, in a 1 to 1 ratio, to receive either galantamine or placebo once a day in the morning. Study drug will first be dispensed at the baseline visit. The treatment phase is composed of a titration period (the study drug will be introduced gradually) and a maintenance period and includes 9 visits (3 of which are conducted by telephone). The titration period is 12 weeks long, and visits occur about every 28 days. In the first 4 weeks of the titration period, subjects will receive either 8 mg galantamine or matching placebo, and this dose will be increased to 16 mg galantamine or placebo in the second 4 weeks. The dose will then be increased to 24 mg galantamine or placebo for the final 4 weeks of the titration period if the investigator believes the subject will benefit from and will safely tolerate 24 mg/day. If not, the subject may continue to receive 16 mg galantamine or placebo through the end of the titration period. After the titration period, subjects will enter the maintenance period and continue to take study drug at the dosage they received at the end of the titration period. This dosage may be continued through the end of the study or may be changed once (either up from 16 to 24 mg or down from 24 to 16 mg), depending upon the benefit and the safety of such a change for the individual patient as judged by the investigator. No dosage will exceed 24 mg/day. The posttreatment phase includes an End-of-Study Visit that occurs at the end of the maintenance period. A follow-up telephone contact (interview) is conducted 1 month after the End-of-Study Visit. The effectiveness of galantamine will be evaluated using the following tools: the Mini-Mental State Examination (MMSE); the Disability Assessment in Dementia (DAD); and the Assessment of Patient Accommodation Status and Caregiver Burden (APAS CarB). Safety evaluations for the study include the monitoring of vital status and institutionalization status, adverse events, vital signs, weight, physical and neurologic examinations. A Data Safety Monitoring Board, external to the company, has been commissioned for this study to monitor the progress of the study and to ensure that the safety of patients is not compromised. The effectiveness hypothesis of this study is that galantamine, 16 to 24 mg per day, is superior to placebo in reducing cognitive decline from baseline (start of study drug) as measured by the MMSE over the course of 2 years. The safety hypothesis is that the mortality rate in the galantamine 16 to 24 mg per day treatment group will be the same as that in the placebo group over the course of 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2051 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-controlled Trial of Long-term (2-year) Treatment of Galantamine in Mild to Moderately-Severe Alzheimer's Disease
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Galantamine Galantamine 8mg/ day oral capsule increased to 16mg/day then to 24 mg per day	Drug: Galantamine; 8mg/ day oral capsule increased to 16mg/day then to 24 mg per day
Placebo Comparator: Placebo Matching placeco	Drug: Placebo; Matching placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Mini-Mental State Examination (MMSE) Score [Baseline, Month 24]

   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.

2. The Number of Deaths Reported in Participants [Up to 2 years]

   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.

Secondary Outcome Measures

1. Change From Baseline in the Mini-Mental State Examination (MMSE) Score [Baseline, Month 6]

   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.

2. Change From Baseline in Disability Assessment in Dementia (DAD) Scores [Baseline, Month 24]

   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.

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

   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.

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

   The table below presents the number of days that caregiving activities were provided during the past week.

5. Change From Baseline in Institutional Status [Baseline, Month 24]

   This table describes the number of participants who were reported as institutionalized at baseline and Month 24.

6. Change From Baseline in the Mini-Mental State Examination (MMSE) Subscales (Orientation, Registration, Attention and Calculation, Recall, and Language) [Baseline, Month 24]

   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.

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

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Outpatients

• diagnosed with mild to moderately-severe, probable or possible AD, established in accordance with the criteria defined by the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease Related Disorders Association or the Diagnostic and Statistical Manual, Fourth Edition

• living with or have regular and frequent visits from a responsible caregiver.

Exclusion Criteria:

• Neurodegenerative disorders other than AD, such as Parkinson's Disease, Frontotemporal Dementia or Huntington's disease

• Any of specified conditions which may contribute to dementia

• any of specified coexisting diseases, including significant cardiovascular disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Hradec Kralove		Czech Republic
2		Mìlník 1		Czech Republic
3		Olomouc		Czech Republic
4		Ostrava 3		Czech Republic
5		Ostrava		Czech Republic
6		Praha 2		Czech Republic
7		Praha 8		Czech Republic
8		Tallinn N/A		Estonia
9		Tallinn		Estonia
10		Tartu		Estonia
11		Viljandi N/A		Estonia
12		Vorumaa		Estonia
13		Limoges		France
14		Bad Aibling		Germany
15		Bad Homburg		Germany
16		Bad Honnef		Germany
17		Bamberg		Germany
18		Berlin		Germany
19		Bielefeld		Germany
20		Bochum		Germany
21		Butzbach		Germany
22		Franfurt		Germany
23		Fürth		Germany
24		Gelsenkirchen		Germany
25		Göttingen		Germany
26		Hamburg		Germany
27		Hannover		Germany
28		Hattingen		Germany
29		Karlstadt		Germany
30		Leverkusen		Germany
31		Lüneburg		Germany
32		Mittweida		Germany
33		Mönchengladbach		Germany
34		Nürnberg		Germany
35		Oldenburg		Germany
36		Ulm		Germany
37		Unterhaching		Germany
38		Westerstede		Germany
39		Wiesbaden		Germany
40		Athens		Greece
41		Heraklion Crete		Greece
42		Thessalonikis		Greece
43		Riga		Latvia
44		Kaunas		Lithuania
45		Siauliai		Lithuania
46		Vilnius		Lithuania
47		Arad		Romania
48		Bucharest Sector 5		Romania
49		Bucharest		Romania
50		Cluj-Napoca		Romania
51		Constanta		Romania
52		Craiova		Romania
53		Iasi		Romania
54		Tg Mures		Romania
55		Ekaterinburg		Russian Federation
56		Kazan N/A		Russian Federation
57		Kazan		Russian Federation
58		Kirov		Russian Federation
59		Krasnodar N/A		Russian Federation
60		Krasnodar		Russian Federation
61		Lipetsk		Russian Federation
62		Moscow Russia		Russian Federation
63		Moscow		Russian Federation
64		Nizny Novgorod		Russian Federation
65		Novosibirsk		Russian Federation
66		Rostov-On-Don		Russian Federation
67		Samara		Russian Federation
68		Saratov		Russian Federation
69		Smolensk Region N/A		Russian Federation
70		Smolensk		Russian Federation
71		St Petersburg		Russian Federation
72		St-Petersburg		Russian Federation
73		St.Petersburg		Russian Federation
74		Tomsk Na		Russian Federation
75		Voronezh		Russian Federation
76		Yaroslavl		Russian Federation
77		Bratislava		Slovakia
78		Dubnica Nad Vahom		Slovakia
79		Kosice		Slovakia
80		Plesivec		Slovakia
81		Senkvice		Slovakia
82		Spisska Nova Ves		Slovakia
83		Vranov Nad Toplou		Slovakia
84		Kamnik		Slovenia
85		Lesce		Slovenia
86		Ljubljana		Slovenia
87		Maribor		Slovenia
88		Chernivtsy		Ukraine
89		Dnepropetrovsk		Ukraine
90		Dnipropetrovsk		Ukraine
91		Donetsk		Ukraine
92		Kharkov		Ukraine
93		Kherson		Ukraine
94		Kiev		Ukraine
95		Kyiv		Ukraine
96		Lviv		Ukraine
97		Lvov		Ukraine
98		Odessa		Ukraine
99		Poltava		Ukraine
100		Simferopol		Ukraine
101		Uzhgorod		Ukraine
102		Vinnitsa		Ukraine

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC C. Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT00679627
• Other Study ID Numbers: CR012463; GALALZ3005
• First Posted: May 19, 2008
• Last Update Posted: Sep 19, 2013
• Last Verified: Sep 1, 2013

• Keywords provided by Janssen Research & Development, LLC: Alzheimer's Disease; Galantamine; Dementia, Alzheimer type; Memory loss
• Additional relevant MeSH terms: Alzheimer Disease; Galantamine

Study Results

Participant Flow

Recruitment Details	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 Detail	The Data Safety Monitoring Board (DSMB) recommended that the study be terminated early because of an imbalance of deaths between the treatment groups.

Arm/Group Title	Placebo	Galantamine
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	1021	1024
COMPLETED	322	339
NOT COMPLETED	699	685

Baseline Characteristics

Arm/Group Title	Placebo	Galantamine	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	1021	1024	2045
Age (participants) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [participants]	73.2 (8.67) 7.2%	73 (8.88) 7.1%	73.1 (8.77) 3.6%
Age, Customized (participants) [Number]
<61	112 11%	112 10.9%	224 11%
61-<76	467 45.7%	466 45.5%	933 45.6%
>=76	442 43.3%	446 43.6%	888 43.4%
Sex: Female, Male (Count of Participants)
Female	654 64.1%	671 65.5%	1325 64.8%
Male	367 35.9%	353 34.5%	720 35.2%
Region of Enrollment (participants) [Number]
Czech Republic	33 3.2%	34 3.3%	67 3.3%
Estonia	53 5.2%	51 5%	104 5.1%
France	10 1%	11 1.1%	21 1%
Germany	218 21.4%	221 21.6%	439 21.5%
Greece	35 3.4%	36 3.5%	71 3.5%
Italy	25 2.4%	24 2.3%	49 2.4%
Latvia	2 0.2%	2 0.2%	4 0.2%
Lithuania	23 2.3%	21 2.1%	44 2.2%
Romania	84 8.2%	84 8.2%	168 8.2%
Russia	274 26.8%	271 26.5%	545 26.7%
Slovakia	85 8.3%	88 8.6%	173 8.5%
Slovenia	13 1.3%	13 1.3%	26 1.3%
Ukraine	166 16.3%	168 16.4%	334 16.3%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Mini-Mental State Examination (MMSE) Score
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Galantamine
Arm/Group Description	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.	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.
Measure Participants	906	906
Mean (Standard Deviation) [Scores on scale]	-2.14 (4.340)	-1.41 (4.050)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galantamine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

2. Primary Outcome

Title	The Number of Deaths Reported in Participants
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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Galantamine
Arm/Group Description	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.	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.
Measure Participants	1021	1024
Number [Number of Participants]	56 5.5%	33 3.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galantamine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95%; 0.37 to 0.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in the Mini-Mental State Examination (MMSE) Score
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Galantamine
Arm/Group Description	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.	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.
Measure Participants	906	906
Mean (Standard Deviation) [Scores on scale]	-0.28 (2.938)	0.15 (2.725)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galantamine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

4. Secondary Outcome

Title	Change From Baseline in Disability Assessment in Dementia (DAD) Scores
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Galantamine
Arm/Group Description	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.	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.
Measure Participants	906	906
Mean (Standard Deviation) [Scores on scale]	-10.81 (18.268)	-8.16 (17.251)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galantamine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	ANCOVA
	Comments

5. Secondary Outcome

Title	Change From Baseline in Patient Accommodation Measured Using the Assessment of Subject Accommodation Status and Caregiver Burden (APAS-CarB)
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Galantamine
Arm/Group Description	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.	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.
Measure Participants	906	906
Home with friend or relative - Baseline	62.1 6.1%	62.8 6.1%
Home with friend or relative - Month 12	61.4 6%	61.8 6%
Home with friend or relative - Month 24	55.3 5.4%	60.1 5.9%

6. Secondary Outcome

Title	Change From Baseline in Caregiver Time Spent With the Patient Measured Using the Assessment of Subject Accommodation Status and Caregiver Burden (APAS-CarB)
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

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants who received at least 1 dose of treatment and had at least 1 postbaseline measure.

Arm/Group Title	Placebo	Galantamine
Arm/Group Description	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.	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.
Measure Participants	906	906
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)

7. Secondary Outcome

Title	Change From Baseline in Institutional Status
Description	This table describes the number of participants who were reported as institutionalized at baseline and Month 24.
Time Frame	Baseline, Month 24

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants who received at least 1 dose of treatment and had at least 1 postbaseline measure.

Arm/Group Title	Placebo	Galantamine
Arm/Group Description	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.	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.
Measure Participants	906	906
Baseline	1 0.1%	0 0%
Month 24	5 0.5%	6 0.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galantamine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.269
	Comments	Baseline
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galantamine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.835
	Comments	Month 24
	Method	Cochran-Mantel-Haenszel
	Comments

8. Secondary Outcome

Title	Change From Baseline in the Mini-Mental State Examination (MMSE) Subscales (Orientation, Registration, Attention and Calculation, Recall, and Language)
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

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants who received at least 1 dose of treatment and had at least 1 postbaseline MMSE measure.

Arm/Group Title	Placebo	Galantamine
Arm/Group Description	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.	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.
Measure Participants	906	906
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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galantamine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.194
	Comments	Orientation subscale
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galantamine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.353
	Comments	Registration subscale
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galantamine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments	Attention and Calculation subscale
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galantamine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.158
	Comments	Recall subscale
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galantamine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.088
	Comments	Language subscale
	Method	ANCOVA
	Comments

9. Secondary Outcome

Title	Change From Baseline in the Disability Assessment in Dementia (DAD) Subscales (Initiation, Planning and Organization, Effective Performance, Basic, Instrumental, and Leisure)
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

Outcome Measure Data

Analysis Population Description

This analysis was performed in the intent-to-treat population which included all randomized participants who had at least 1 postbaseline DAD measure.

Arm/Group Title	Placebo	Galantamine
Arm/Group Description	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.	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.
Measure Participants	906	906
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

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galantamine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments	Initiation subscale
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galantamine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.043
	Comments	Planning and Organization subscale
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galantamine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.018
	Comments	Effective Performance subscale
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galantamine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments	Basic subscale
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galantamine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.054
	Comments	Instrumental subscale
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galantamine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.137
	Comments	Leisure subscale
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	Over 2 years
Arm/Group Title	Placebo		Galantamine
Arm/Group Description	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.		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.
All Cause Mortality
	Placebo		Galantamine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Galantamine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	123/1021 (12%)		129/1024 (12.6%)
Blood and lymphatic system disorders
Anaemia	1/1021 (0.1%)		0/1024 (0%)
Cardiac disorders
Acute Myocardial Infarction	1/1021 (0.1%)		1/1024 (0.1%)
Arrhythmia	1/1021 (0.1%)		0/1024 (0%)
Arteriosclerosis Coronary Artery	0/1021 (0%)		1/1024 (0.1%)
Atrial Fibrillation	1/1021 (0.1%)		1/1024 (0.1%)
Bradyarrhythmia	0/1021 (0%)		1/1024 (0.1%)
Bradycardia	1/1021 (0.1%)		1/1024 (0.1%)
Cardiac Arrest	1/1021 (0.1%)		0/1024 (0%)
Cardiac Failure	3/1021 (0.3%)		10/1024 (1%)
Cardiac Failure Acute	2/1021 (0.2%)		2/1024 (0.2%)
Cardio-Respiratory Arrest	3/1021 (0.3%)		0/1024 (0%)
Cardiopulmonary Failure	4/1021 (0.4%)		3/1024 (0.3%)
Cardiovascular Insufficiency	3/1021 (0.3%)		1/1024 (0.1%)
Ischaemic Cardiomyopathy	0/1021 (0%)		1/1024 (0.1%)
Myocardial Infarction	2/1021 (0.2%)		6/1024 (0.6%)
Myocardial Ischaemia	1/1021 (0.1%)		1/1024 (0.1%)
Postinfarction Angina	0/1021 (0%)		1/1024 (0.1%)
Tachyarrhythmia	1/1021 (0.1%)		0/1024 (0%)
Ear and labyrinth disorders
Vertigo	0/1021 (0%)		1/1024 (0.1%)
Eye disorders
Cataract	0/1021 (0%)		2/1024 (0.2%)
Cataract Subcapsular	0/1021 (0%)		1/1024 (0.1%)
Glaucoma	0/1021 (0%)		2/1024 (0.2%)
Lens Disorder	0/1021 (0%)		1/1024 (0.1%)
Gastrointestinal disorders
Anal Polyp	1/1021 (0.1%)		0/1024 (0%)
Colitis Ischaemic	1/1021 (0.1%)		0/1024 (0%)
Diarrhoea	1/1021 (0.1%)		0/1024 (0%)
Duodenal Ulcer Perforation	0/1021 (0%)		1/1024 (0.1%)
Dysphagia	0/1021 (0%)		1/1024 (0.1%)
Enterocolitis	1/1021 (0.1%)		0/1024 (0%)
Enterocolitis Haemorrhagic	0/1021 (0%)		1/1024 (0.1%)
Faecal Incontinence	0/1021 (0%)		1/1024 (0.1%)
Gastric Ulcer	0/1021 (0%)		1/1024 (0.1%)
Gastric Ulcer Haemorrhage	0/1021 (0%)		1/1024 (0.1%)
Gastroduodenitis	0/1021 (0%)		2/1024 (0.2%)
Haemorrhagic Erosive Gastritis	1/1021 (0.1%)		0/1024 (0%)
Haemorrhoidal Haemorrhage	1/1021 (0.1%)		0/1024 (0%)
Haemorrhoids	1/1021 (0.1%)		0/1024 (0%)
Ileus	0/1021 (0%)		1/1024 (0.1%)
Inguinal Hernia	0/1021 (0%)		2/1024 (0.2%)
Intestinal Stenosis	0/1021 (0%)		1/1024 (0.1%)
Nausea	0/1021 (0%)		1/1024 (0.1%)
Oesophageal Achalasia	0/1021 (0%)		1/1024 (0.1%)
Pancreatitis	0/1021 (0%)		1/1024 (0.1%)
Peritoneal Haemorrhage	0/1021 (0%)		1/1024 (0.1%)
Upper Gastrointestinal Haemorrhage	1/1021 (0.1%)		0/1024 (0%)
Varices Oesophageal	0/1021 (0%)		1/1024 (0.1%)
Vomiting	1/1021 (0.1%)		1/1024 (0.1%)
General disorders
Abasia	0/1021 (0%)		1/1024 (0.1%)
Death	1/1021 (0.1%)		0/1024 (0%)
Hypothermia	2/1021 (0.2%)		0/1024 (0%)
Inflammation	1/1021 (0.1%)		0/1024 (0%)
Multi-Organ Failure	1/1021 (0.1%)		0/1024 (0%)
Oedema Peripheral	0/1021 (0%)		1/1024 (0.1%)
Pyrexia	1/1021 (0.1%)		1/1024 (0.1%)
Sudden Death	3/1021 (0.3%)		1/1024 (0.1%)
Hepatobiliary disorders
Bile Duct Stone	0/1021 (0%)		1/1024 (0.1%)
Cholecystitis	1/1021 (0.1%)		2/1024 (0.2%)
Infections and infestations
Abscess	1/1021 (0.1%)		0/1024 (0%)
Bronchitis	0/1021 (0%)		2/1024 (0.2%)
Bronchopneumonia	3/1021 (0.3%)		2/1024 (0.2%)
Clostridium Difficile Colitis	1/1021 (0.1%)		0/1024 (0%)
Ear Infection	0/1021 (0%)		1/1024 (0.1%)
Gastroenteritis Rotavirus	1/1021 (0.1%)		0/1024 (0%)
Gastrointestinal Infection	0/1021 (0%)		1/1024 (0.1%)
Herpes Zoster	1/1021 (0.1%)		2/1024 (0.2%)
Peritonitis	0/1021 (0%)		1/1024 (0.1%)
Pneumonia	6/1021 (0.6%)		8/1024 (0.8%)
Post Procedural Infection	0/1021 (0%)		1/1024 (0.1%)
Sepsis	1/1021 (0.1%)		0/1024 (0%)
Tuberculosis	1/1021 (0.1%)		0/1024 (0%)
Urinary Tract Infection	1/1021 (0.1%)		1/1024 (0.1%)
Urosepsis	0/1021 (0%)		1/1024 (0.1%)
Injury, poisoning and procedural complications
Accidental Overdose	1/1021 (0.1%)		0/1024 (0%)
Carbon Monoxide Poisoning	1/1021 (0.1%)		0/1024 (0%)
Chemical Poisoning	0/1021 (0%)		1/1024 (0.1%)
Exposure to Toxic Agent	0/1021 (0%)		1/1024 (0.1%)
Fall	3/1021 (0.3%)		2/1024 (0.2%)
Femoral Neck Fracture	3/1021 (0.3%)		2/1024 (0.2%)
Femur Fracture	3/1021 (0.3%)		3/1024 (0.3%)
Forearm Fracture	1/1021 (0.1%)		1/1024 (0.1%)
Hand Fracture	0/1021 (0%)		1/1024 (0.1%)
Head Injury	2/1021 (0.2%)		1/1024 (0.1%)
Hip Fracture	3/1021 (0.3%)		1/1024 (0.1%)
Humerus Fracture	1/1021 (0.1%)		2/1024 (0.2%)
Injury	1/1021 (0.1%)		0/1024 (0%)
Joint Dislocation	1/1021 (0.1%)		1/1024 (0.1%)
Lower Limb Fracture	0/1021 (0%)		2/1024 (0.2%)
Lumbar Vertebral Fracture	0/1021 (0%)		1/1024 (0.1%)
Multiple Fractures	1/1021 (0.1%)		0/1024 (0%)
Patella Fracture	0/1021 (0%)		1/1024 (0.1%)
Rib Fracture	0/1021 (0%)		1/1024 (0.1%)
Skeletal Injury	0/1021 (0%)		1/1024 (0.1%)
Spinal Fracture	1/1021 (0.1%)		0/1024 (0%)
Subdural Haematoma	1/1021 (0.1%)		0/1024 (0%)
Subdural Haemorrhage	0/1021 (0%)		1/1024 (0.1%)
Upper Limb Fracture	1/1021 (0.1%)		0/1024 (0%)
Urethral Injury	0/1021 (0%)		1/1024 (0.1%)
Wound Haemorrhage	1/1021 (0.1%)		0/1024 (0%)
Investigations
Blood Pressure Increased	0/1021 (0%)		1/1024 (0.1%)
Weight Decreased	0/1021 (0%)		1/1024 (0.1%)
Metabolism and nutrition disorders
Decreased Appetite	0/1021 (0%)		1/1024 (0.1%)
Dehydration	1/1021 (0.1%)		4/1024 (0.4%)
Diabetes Mellitus	2/1021 (0.2%)		2/1024 (0.2%)
Hyperglycaemia	1/1021 (0.1%)		0/1024 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	2/1021 (0.2%)		1/1024 (0.1%)
Bone Pain	1/1021 (0.1%)		0/1024 (0%)
Intervertebral Disc Compression	1/1021 (0.1%)		0/1024 (0%)
Muscular Weakness	0/1021 (0%)		1/1024 (0.1%)
Musculoskeletal Pain	2/1021 (0.2%)		1/1024 (0.1%)
Osteoarthritis	0/1021 (0%)		2/1024 (0.2%)
Spinal Column Stenosis	0/1021 (0%)		1/1024 (0.1%)
Spinal Osteoarthritis	0/1021 (0%)		1/1024 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma Pancreas	1/1021 (0.1%)		0/1024 (0%)
Breast Cancer	1/1021 (0.1%)		1/1024 (0.1%)
Colon Cancer	1/1021 (0.1%)		1/1024 (0.1%)
Hepatic Neoplasm Malignant	1/1021 (0.1%)		0/1024 (0%)
Pancreatic Neoplasm	1/1021 (0.1%)		0/1024 (0%)
Pharyngeal Neoplasm	1/1021 (0.1%)		0/1024 (0%)
Prostatic Adenoma	1/1021 (0.1%)		0/1024 (0%)
Rectal Cancer	0/1021 (0%)		1/1024 (0.1%)
Salivary Gland Adenoma	1/1021 (0.1%)		0/1024 (0%)
Nervous system disorders
Altered State of Consciousness	1/1021 (0.1%)		0/1024 (0%)
Cerebral Arteriosclerosis	0/1021 (0%)		1/1024 (0.1%)
Cerebral Haemorrhage	1/1021 (0.1%)		1/1024 (0.1%)
Cerebral Infarction	2/1021 (0.2%)		1/1024 (0.1%)
Cerebrovascular Accident	2/1021 (0.2%)		4/1024 (0.4%)
Cerebrovascular Disorder	1/1021 (0.1%)		1/1024 (0.1%)
Coma	0/1021 (0%)		1/1024 (0.1%)
Dementia	2/1021 (0.2%)		0/1024 (0%)
Dementia Alzheimer's Type	12/1021 (1.2%)		9/1024 (0.9%)
Diabetic Neuropathy	1/1021 (0.1%)		0/1024 (0%)
Epilepsy	3/1021 (0.3%)		0/1024 (0%)
Haemorrhage Intracranial	1/1021 (0.1%)		0/1024 (0%)
Haemorrhagic Stroke	1/1021 (0.1%)		0/1024 (0%)
Ischaemic Stroke	8/1021 (0.8%)		2/1024 (0.2%)
Loss of Consciousness	1/1021 (0.1%)		3/1024 (0.3%)
Polyneuropathy	1/1021 (0.1%)		0/1024 (0%)
Presyncope	0/1021 (0%)		1/1024 (0.1%)
Speech Disorder	0/1021 (0%)		1/1024 (0.1%)
Syncope	3/1021 (0.3%)		3/1024 (0.3%)
Transient Ischaemic Attack	3/1021 (0.3%)		2/1024 (0.2%)
Vertebrobasilar Insufficiency	0/1021 (0%)		1/1024 (0.1%)
Psychiatric disorders
Abnormal Behaviour	1/1021 (0.1%)		0/1024 (0%)
Adjustment Disorder	0/1021 (0%)		1/1024 (0.1%)
Aggression	1/1021 (0.1%)		3/1024 (0.3%)
Agitation	2/1021 (0.2%)		1/1024 (0.1%)
Catatonia	0/1021 (0%)		1/1024 (0.1%)
Confusional State	0/1021 (0%)		1/1024 (0.1%)
Delirium	1/1021 (0.1%)		1/1024 (0.1%)
Depression	0/1021 (0%)		1/1024 (0.1%)
Disorientation	0/1021 (0%)		1/1024 (0.1%)
Psychotic Disorder	0/1021 (0%)		2/1024 (0.2%)
Restlessness	1/1021 (0.1%)		0/1024 (0%)
Suicide Attempt	0/1021 (0%)		1/1024 (0.1%)
Renal and urinary disorders
Incontinence	1/1021 (0.1%)		0/1024 (0%)
Nephritis	1/1021 (0.1%)		0/1024 (0%)
Renal Failure Acute	0/1021 (0%)		1/1024 (0.1%)
Renal Failure Chronic	1/1021 (0.1%)		0/1024 (0%)
Stress Urinary Incontinence	0/1021 (0%)		1/1024 (0.1%)
Tubulointerstitial Nephritis	1/1021 (0.1%)		0/1024 (0%)
Urinary Incontinence	0/1021 (0%)		1/1024 (0.1%)
Urinary Retention	1/1021 (0.1%)		1/1024 (0.1%)
Reproductive system and breast disorders
Benign Prostatic Hyperplasia	0/1021 (0%)		2/1024 (0.2%)
Pelvic Pain	0/1021 (0%)		1/1024 (0.1%)
Scrotal Disorder	1/1021 (0.1%)		0/1024 (0%)
Vulval Leukoplakia	1/1021 (0.1%)		0/1024 (0%)
Respiratory, thoracic and mediastinal disorders
Acute Lung Injury	0/1021 (0%)		1/1024 (0.1%)
Aspiration	0/1021 (0%)		1/1024 (0.1%)
Bronchitis Chronic	0/1021 (0%)		1/1024 (0.1%)
Chronic Obstructive Pulmonary Disease	0/1021 (0%)		1/1024 (0.1%)
Dyspnoea	1/1021 (0.1%)		2/1024 (0.2%)
Emphysema	0/1021 (0%)		1/1024 (0.1%)
Pneumonia Aspiration	1/1021 (0.1%)		0/1024 (0%)
Pneumothorax	0/1021 (0%)		1/1024 (0.1%)
Pulmonary Embolism	1/1021 (0.1%)		5/1024 (0.5%)
Pulmonary Oedema	1/1021 (0.1%)		0/1024 (0%)
Respiratory Failure	0/1021 (0%)		1/1024 (0.1%)
Skin and subcutaneous tissue disorders
Decubitus Ulcer	1/1021 (0.1%)		0/1024 (0%)
Psoriasis	1/1021 (0.1%)		0/1024 (0%)
Rash	0/1021 (0%)		1/1024 (0.1%)
Surgical and medical procedures
Carotid Artery Stent Removal	1/1021 (0.1%)		0/1024 (0%)
Vascular disorders
Arteriosclerosis	0/1021 (0%)		1/1024 (0.1%)
Circulatory Collapse	1/1021 (0.1%)		0/1024 (0%)
Essential Hypertension	0/1021 (0%)		2/1024 (0.2%)
Haemorrhagic Infarction	0/1021 (0%)		1/1024 (0.1%)
Hypertension	1/1021 (0.1%)		1/1024 (0.1%)
Hypertensive Crisis	0/1021 (0%)		1/1024 (0.1%)
Hypotension	1/1021 (0.1%)		0/1024 (0%)
Malignant Hypertension	1/1021 (0.1%)		1/1024 (0.1%)
Pallor	1/1021 (0.1%)		0/1024 (0%)
Peripheral Arterial Occlusive Disease	1/1021 (0.1%)		0/1024 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Galantamine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	115/1021 (11.3%)		168/1024 (16.4%)
Ear and labyrinth disorders
Vertigo	48/1021 (4.7%)		57/1024 (5.6%)
Gastrointestinal disorders
Nausea	24/1021 (2.4%)		85/1024 (8.3%)
Nervous system disorders
Headache	58/1021 (5.7%)		58/1024 (5.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.