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
  Purpose

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 Intervention Phase
Alzheimer's Disease
Drug: Galantamine
Drug: Placebo
Phase 3

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
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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Change From Baseline in the Mini-Mental State Examination (MMSE) Score [ Time Frame: Baseline, Month 24 ] [ Designated as safety issue: No ]
    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.

  • The Number of Deaths Reported in Participants [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    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:
  • Change From Baseline in the Mini-Mental State Examination (MMSE) Score [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Disability Assessment in Dementia (DAD) Scores [ Time Frame: Baseline, Month 24 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    The table below presents the number of days that caregiving activities were provided during the past week.

  • Change From Baseline in Institutional Status [ Time Frame: Baseline, Month 24 ] [ Designated as safety issue: No ]
    This table describes the number of participants who were reported as institutionalized at baseline and Month 24.

  • Change From Baseline in the Mini-Mental State Examination (MMSE) Subscales (Orientation, Registration, Attention and Calculation, Recall, and Language) [ Time Frame: Baseline, Month 24 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 2051
Study Start Date: June 2008
Study Completion Date: May 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   45 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00679627

  Show 102 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC C. Clinical Trial Janssen Research & Development, LLC
  More Information

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

Keywords provided by Janssen Research & Development, LLC:
Alzheimer's Disease
Galantamine
Dementia, Alzheimer type
Memory loss

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Galantamine
Parasympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on July 24, 2014