Safety and Efficacy of High Dose, Rapid Titration Galantamine in Patients With Alzheimer's Disease

NCT ID: NCT00338117

Last Updated: 2010-04-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 554 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1995-08-31
• Study Completion Date: 1997-05-31

Brief Summary

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.

Detailed Description

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.

Conditions

Alzheimer's Disease; Dementia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

Galantamine hydrobromide

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: collaborator

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

INDUSTRY

Sponsor Role: lead

Principal Investigators

Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial

Role: STUDY_DIRECTOR

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Other Identifiers

CR005884

Identifier Type: -

Identifier Source: org_study_id