Clinical trial NCT00253188: A Study of the Safety and Effectiveness of Two Doses of Galantamine Versus Placebo in the Treatment of Patients With Alzheimer's Disease
Official title: Efficacy, Tolerability and Safety of Galantamine in the Treatment of Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer Disease
Dementia
Keywords: Alzheimer's disease
dementia
brain disease
memory loss
galantamine
placebo
caregiver
quality of life
resource utilization
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2005-11-15
Enrollment: 653
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and effectiveness of two doses of galantamine (a drug for treating dementia) versus placebo in the treatment of patients with Alzheimer's disease.

Detailed description: Dementia is a chronic, progressive brain disease that may involve a number of symptoms, including memory loss and changes in personality, behavior, judgment, attention span, language and thought. The most common type of dementia is Alzheimer's disease. Over time, patients with Alzheimer's disease may lose ability to perform daily tasks related to personal care (for example bathing, dressing, eating) and may be unable to handle money or travel to familiar places. Several small clinical trials have shown galantamine to be safe and effective in treating the symptoms associated with Alzheimer's disease. Doses studied have ranged from 15 - 60 mg/day, with galantamine administered two or three times daily. Additional information is needed to determine the optimal dose regimen for galantamine in the treatment of Alzheimer's' disease. This multicenter, double-blind, placebo-controlled (neither the patient nor the study doctor know the dose of galantamine being given) study evaluates the safety and effectiveness of two doses of galantamine, each given twice daily, in the treatment of patients with Alzheimer's disease. All patients initially receive placebo for a 1-month period and then receive one of two doses of galantamine (beginning at 4 mg twice daily and gradually increasing to 12 or 16 mg twice daily) or placebo for 6 months. The primary measures of effectiveness include the change from baseline to the end of treatment in the ADAS-cog/11 score (Alzheimer's Disease Assessment Scale: sum of 11 cognitive items) and the CIBIC-plus score (Clinician's Interview Based Impression of Change - Plus Caregiver Input). Additional measures of effectiveness assessed at the end of the treatment include the ADAS-cog/13 score (Alzheimer's Disease Assessment Scale: sum of 13 cognitive items) and the Disability Assessment for Dementia (DAD) score. Safety evaluations (incidence of adverse events, electrocardiograms (ECGs), physical examinations, laboratory tests) are performed throughout the study. Caregiver quality of life (Psychological General Well Being Index, \[PGWB\]) and health/social care resource utilization (physician and other health care professional visits, use of social services, etc.) are also assessed throughout the study by questionnaires answered by the caregivers. Blood samples are taken throughout the study to determine the concentration of drug in the blood. Patients may also participate in an optional portion of the study in which their genetic material is analyzed to see if contains something that would affect the way galantamine is used by their bodies. The study hypothesis is that galantamine administered in either dose is effective in the treatment of Alzheimer's disease as compared with placebo, and is well tolerated. This study will be conducted internationally. A companion study of exact design will be conducted in the United States. Galantamine tablets (or placebo), taken orally twice daily for 6 months beginning with 4 mg twice daily and gradually increasing to 12 or 16 mg twice daily.

Eligibility criteria: Inclusion Criteria:

* Outpatients with a diagnosis of Alzheimer's disease according to the National Institute of Neurological and Communicative Disorders and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria (including patients living independently in residential homes for the elderly or day patients)
* have mild to moderate dementia, as evidenced by a Mini-Mental Status Examination (MMSE) score of 11 - 24 and a score of at least 12 on the cognitive portion of the Alzheimer's Disease Assessment scale (ADAS-cog)
* history of at least a 6 months of gradual and progressive cognitive decline
* have a consistent informant to accompany the patient on scheduled visits

Exclusion Criteria:

* Neurogenerative disorders such as Parkinson's disease
* dementia caused by small strokes or cerebrovascular disease
* cognitive impairment resulting from acute cerebral trauma, cerebral damage due to a lack of oxygen, vitamin deficiency, infections such as meningitis or AIDS, significant endocrine or metabolic disease, mental retardation or a brain tumor
* having epilepsy, significant psychiatric disease, active peptic ulcer, clinically significant liver, kidney, or lung disorders, or heart disease
* Females of child bearing potential without adequate contraception

Primary outcomes:
measure: Change from baseline to the end of treatment in ADAS-cog/11 (Alzheimer's Disease Assessment Scale: sum of 11 cognitive items) and CIBIC-plus (Clinician's Interview Based Impression of Change - Plus Caregiver Input) scores
Secondary outcomes:
measure: Change from baseline in ADAS-cog/13 and DAD scores to the end of treatment; concentration of drug in blood; PGWB; Health/social care resource use; Incidence of adverse events; Changes in laboratory tests, ECGs and physical examinations
Other outcomes:
Locations:
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Wilcock GK, Lilienfeld S, Gaens E. Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: multicentre randomised controlled trial. Galantamine International-1 Study Group. BMJ. 2000 Dec 9;321(7274):1445-9. doi: 10.1136/bmj.321.7274.1445.
citation: Pirttila T, Wilcock G, Truyen L, Damaraju CV. Long-term efficacy and safety of galantamine in patients with mild-to-moderate Alzheimer's disease: multicenter trial. Eur J Neurol. 2004 Nov;11(11):734-41. doi: 10.1111/j.1468-1331.2004.00885.x.