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

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

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

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).

Detailed Summary: 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 o
Sponsor: Janssen Research & Development, LLC

Current Primary Outcome:

• Change From Baseline in the Mini-Mental State Examination (MMSE) Score [ Time Frame: 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.
• The Number of Deaths Reported in Participants [ Time Frame: 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.

Original Primary Outcome: The primary efficacy criterion is the cognitive change from baseline as measured by the MMSE score at Month 24 for subjects treated with galantamine compared with those treated with matching placebo. [ Time Frame: The primary efficacy criterion is the cognitive change from baseline as measured by the MMSE score at Month 24 for subjects treated with galantamine compared with those treated with matching placebo. ]

Current Secondary Outcome:

• Change From Baseline in the Mini-Mental State Examination (MMSE) Score [ Time Frame: 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.
• Change From Baseline in Disability Assessment in Dementia (DAD) Scores [ Time Frame: 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.
• 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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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.

Original Secondary Outcome: Cognitive change from baseline to Month 6 in the MMSE; change from baseline to Month 24 in DAD scores; and using the APAS-CarB, the time to change over the study in subject accommodation and time caregiver spent with subject over the previous 3 months [ Time Frame: Assess cognitive change from baseline to Month 6 in the MMSE; change from baseline to Month 24 in DAD scores; and using the APAS-CarB, the time to change over the study in subject accommodation and time caregiver spent with subject over 3 months ]

Information By: Janssen Research & Development, LLC

Dates:
Date Received: May 15, 2008
Date Started: June 2008
Date Completion:
Last Updated: September 10, 2013
Last Verified: September 2013