Clinical trial NCT00304629: Long-term Safety and Efficacy of Galantamine in Alzheimer's Disease
Official title: Long Term Safety and Efficacy of Galantamine in Alzheimer's Disease (Extension INT-8)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer Disease
Keywords: Alzheimer's disease
cholinesterase inhibitors
galantamine
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2006-03-20
Enrollment: 241
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The long-term safety and efficacy of galantamine (12 mg bid) will be documented during a one year open-label treatment in subjects with Alzheimer's Disease who completed the GAL-INT-8 trial (up to 400 eligible patients). Safety will be tracked by means of adverse event reports, laboratory parameters and physical exam. Long-term efficacy will be evaluated by means of a Alzheimer's Disease Assessment Scale(ADAS) and activities of daily living scale Disability Assessment for Dementia Scale(DAD)

Detailed description: This is a twelve-month, open-label trial in which treatment with 12 mg bid galantamine will be evaluated. Only subjects who took trial medication during the 24-month trial period of GAL-INT-8 will be eligible. Safety will be assessed by periodic physical examination, vital signs, ECG and laboratory tests and reports of adverse events. The ADAS-cognitive scale and DAD scale will be used to document long-term efficacy.

Patients will be seen at 6 monthly intervals but the ADAS-cognitive scale and DAD scale will only be performed at end of trial. The treatment will consist of tablets which will contain 12 mg of galantamine. Duration of treatment equals 12 months. Patients will receive 1 tablet twice daily preferably to be taken with food (breakfast in the morning at approximately 8 AM and a snack or meal in the evening at approximately 6PM).

Eligibility criteria: Inclusion Criteria:

* Patients must have taken trial medication during the 24-month trial period of GAL-INT-8 and should be enrolled within 1 month after completion
* Patients and their primary caregiver give informed consent for the participation in the trial
* Patients must have remained in good health, as determined by medical history, complete physical examination and laboratory tests

Exclusion Criteria:

* If a patient developed, during the trial GAL-INT-8, symptoms of other neurological or psychiatric diseases that might contribute to dementia, the subject cannot be enrolled. This includes subjects developing neurodegenerative disorders such as Parkinson's disease, Pick's disease or Huntington's chorea, or Creutzfeldt-Jacob disease, and subjects with cognitive impairment resulting from stroke, acute cerebral trauma, hypoxic cerebral damage, infection or primary or metastatic cerebral neoplasia
* Subjects with the following co-existing medical conditions: a) Any history of epilepsy or convulsions except for febrile convulsions during childhood b) Peptic ulcer: if the ulcer is considered to be still "active", i.e., if treatment for this condition started \<3 months ago or if treatment is not successful (symptoms still present), the subject is not eligible. c) Clinically significant hepatic, renal, pulmonary, metabolic or endocrine disturbances
* Patients with current, clinically significant cardiovascular disease that would be expected to limit the subject's ability to complete a 12-month trial. The following would usually be considered clinically significant cardiovascular disease: a) Unstable angina
* angina or coronary artery disease that required a change in medication (anti-angina or digitalis) within the last 3 months b) Decompensated congestive heart failure i.e. when symptoms occur in a subject on stable medication during rest or light exercise (NYHA III and IV). Note: if the only signs of decompensation are pretibial or malleolar oedema and the exercise tolerance is still reasonable (absence of dyspnoea) the subject should not be excluded c) Cardiac disease potentially resulting in syncope, near syncope or other alterations of mental status
* In addition, the following conditions should lead to exclusion: atrial fibrillation without prophylactic treatment to prevent thromboembolic stroke, bradycardia \<50 beats/min., atrioventricular block \> first degree. d) Severe mitral or aortic valvular disease e) Hypotension or treatment for hypotension f) Systolic blood pressure greater than 170 mmHg or diastolic blood pressure greater than 110 mmHg
* Patients using any agent for the treatment of dementia (approved, experimental, including over the counter agents), including, but not limited to nootropic agents, cholinomimetic agents, choline, oestrogens taken without medical need, chronic NSAIDs (30 consecutive days), vitamin E more than 30 IU daily, and deprenyl
* Conditions that could interfere with the absorption of the compound or with the evaluation of the disease

Primary outcomes:
measure: The primary outcome is safety as measured by adverse events, laboratory tests, vital signs, weight, physical exam and electrocardiogram
Secondary outcomes:
measure: The secondary outcome is effectiveness as measured by a cognitive scale (ADAS) and by activities of daily living (DAD).
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: Rockwood K, Dai D, Mitnitski A. Patterns of decline and evidence of subgroups in patients with Alzheimer's disease taking galantamine for up to 48 months. Int J Geriatr Psychiatry. 2008 Feb;23(2):207-14. doi: 10.1002/gps.1864.