Official Title: “A European Multi-Center Study to Determine the Safety and Efficacy of Galanthamine Hydrobromide 40mg/Day (32 mg /Day GAL Base, Tid Dose Regimen) in Patients Diagnosed With Alzheimer-Type Dementia”

The purpose of this study was to determine the safety and effectiveness of a relatively high dose of galantamine, 32 mg /day in a three-times daily dosage, compared with placebo in treating patients with Alzheimer's disease.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

Alzheimer's disease is a progressive degenerative brain disorder that affects memory, as well as the ability to concentrate, reason, and think in abstract form. This study was designed to examine the effectiveness and safety of galantamine (galant.) hydrobromide at a relatively high dose, compared with treatment with placebo, in men and women with Alzheimer's disease.

Approximately 600 patients were screened. This was a double-blind study, i.e., neither patients nor investigators knew what treatment was given. Before the start of the double-blind phase, each patient was randomly assigned to receive either galantamine hydrobromide or placebo (i.e., no active drug). The dose was increased weekly, at a higher rate than currently recommended in the label, until the stable daily dose of 32 mg galantamine was reached. All patients took their treatment (galantamine or placebo) 3 times a day. All patients who completed the blinded phase of the study were permitted to enter an open-label phase, in which the treatment was made known to both investigators and patients.

During this additional 24-week phase, all patients received treatment with galantamine hydrobromide. The effectiveness of study treatment (galantamine hydrobromide or placebo) was assessed using several measures and included the Mini Mental State Examination (MMSE) score.

The MMSE consists of 12 questions and tasks designed to assess severity of Alzheimer's disease. Additional measures included the European Alzheimer Disease Assessment Scale cognitive score (EURO-ADAS-cog), a Clinician's Interview Based Impression of Change (CIBIC) plus, and the Nurses' Observation Scale for Geriatric Patients (NOSGER). Safety and tolerability were assessed using physical (full and brief) examination, adverse events reports, clinical and laboratory measures, and 12-lead ECG results.

Galant. was taken orally as a tablet 3 times a day with meals. Patients started their treatment with a total 8 mg of galantamine. The dose was increased weekly to a daily cumulative dose of 32 mg (the same as 40 mg Gal HBr).This dose was higher and the titration schedule was 4 times more rapid that the 16 mg and 24 mg maintenance doses and 4-weekly titration steps specified in the US label. Each phase had a 5-week titration period. After 5 weeks, patients continued to receive 40 mg.

Intervention(s) in this Clinical Trial

• Drug: Galantamine hydrobromide

Primary Measures

• The primary outcomes included evaluations by EURO-ADAS cognitive score, CIBIC Plus, and NOSGER at 6 months.

Secondary Measures

• EURO-ADAS non-cognitive score; MMSE; Short Cognitive Performance Test (SKT) sub-set 6; Neuropsychological Assessment Battery (NAB); incidence of adverse events, changes in laboratory measures, results of physical exams, and results of 12-lead ECG.

Inclusion Criteria:

• Have been meeting the diagnostic criteria of Alzheimer's disease
• Mild or moderate dementia as measured by the Mini Mental State Examination (MMSE) score
• Live with or have daily visits from a responsible caregiver

Exclusion Criteria:

• Parkinson's disease
• Pick's disease
• Secondary or pseudodementias
• Currently diagnosed epilepsy
• History of endocrine disorder
• Significant heart disease
• Drug or alcohol abuse
• Kidney or liver dysfunction
• Women of child-bearing potential unless appropriate birth-control method is used
• Sensitivity to the study drug

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 45 Years

Maximum Age for this Clinical Trial: N/A

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.  

Information obtained from ClinicalTrials.gov on November 19, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00338117

Study ID Number: CR005884

ClinicalTrials.gov Identifier: NCT00338117

Health Authority: United States: Food and Drug Administration