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”

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).

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: August 2014

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 subjects will participate in this study. The study length for each subject 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 subject 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 subjects 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 drug is titrated starting at 8 mg/day galantamine oral capsules or matching placebo for 4 weeks, increased to 16 mg/day galantamine or placebo for 4 weeks, followed by a possible increase to 24 mg/day galantamine capsules or placebo for 4 weeks. The end dosage of this sequence is continued for the remainder of the 2-year study; however, 1 change (up from 16 to 24 mg/day or down from 24 to 16 mg/day) is allowed if the investigator judges this potentially beneficial and safe for the subject.

Intervention(s) in this Clinical Trial

• Drug: Galantamine
  • 8mg/ day oral capsule increased to 16mg/day then to 24 mg per day
• Drug: Placebo
  • N/A

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 001
• Placebo Comparator: 002

Primary Measures

• 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.
    Safety Issue?: Yes

Secondary Measures

• 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
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 45 Years

Maximum Age for this Clinical Trial: 90 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Overall Clinical Trial Officials and Contacts

Johnson & Johnson Pharmaceutical Research and Development, L.L.C. Clinical Trial Study Director Johnson & Johnson Pharmaceutical Research & Development, L.L.C.  

Overall Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:  info1@veritasmedicine.com

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00679627

Study ID Number: CR012463

ClinicalTrials.gov Identifier: NCT00679627

Health Authority: United States: Institutional Review Board

To learn how to participate in this trial please click here.