efficacy and safety of lornoxicam in patients with mild to moderate probable alzheimer´s disease.

Conditions: Alzheimer´s Disease

Summary: study title: a multicentre double-blind, placebo-controlled, randomised, parallel-group study to evaluate the safety and efficacy of lornoxicam in patients with mild to moderate probable alzheimer's disease. study phase: ii indication: alzheimer´s disease investigational product, dose schedule and route of administration: lornoxicam (8 mg) tablets to be taken orally two times daily (bid) for a period of 6 months. reference product, dose, schedule and route of administration: placebo (8 mg) tablets to be taken orally two times daily (bid) for a period of 6 months.

study title: a multicentre double-blind, placebo-controlled, randomised, parallel-group study to evaluate the safety and efficacy of lornoxicam in patients with mild to moderate probable alzheimer's disease. study phase: ii indication: alzheimer´s disease study objectives: primary: to evaluate the efficacy of lornoxicam (8 mg, bid) administered for 6 months versus matched placebo based on the following end-point: • cognitive performance - adas-cog+ secondary: to evaluate the efficacy of lornoxicam (8 mg, bid) administered for 6 months versus matched placebo based on the following end-point: * activities of daily living - adcs-adl * behavioral / psychiatric symptoms - npi to evaluate the safety of lornoxicam (8 mg, bid) administered for 6 months versus matched placebo. • overall incidence of adverse events. exploratory: in a subgroup of 50 patients mri analyses will be performed. in a subgroup of 50 patients exploratory data on the production of amyloid biological markers - blood plasma concentration of aß1-38, aß1-40 and aß1-42 will be collected. an optional 6 month open-label phase will be available. subject population, diagnosis and main criteria for inclusion: male and female patients with mild to moderate probable alzheimer's disease according to nincds-adrda criteria * age 50 - 85 years inclusive * mmse 18-26 inclusive * no history of treatment with acetylcholine-esterase inhibitors or 4 weeks wash out period before baseline visit. * no history of treatment with memantine or 4 weeks wash out period before baseline visit. duration of treatment: 6 month double-blind phase 6 month open-label phase (optional) total number of subjects: a total of 220 patients will be recruited to the study from approximately 20 centers in a treatment ratio of 1:1 (8 mg bid, 110 : placebo, 110). this reflects the minimum number of patients required and also allows for a drop out rate of approximately 20%. additional subjects may be recruited based on interim analysis. number of study centres: approximately 20; multinational europe number of visits: doubble-blind phase: 5 visits (including screening); open-label phase: 3 visits investigational product, dose schedule and route of administration: lornoxicam (8 mg) tablets to be taken orally two times daily (bid) for a period of 6 months. reference product, dose, schedule and route of administration: placebo (8 mg) tablets to be taken orally two times daily (bid) for a period of 6 months.

Eligibility criteria:
inclusion criteria: 1. men and women (non-childbearing potential) with a diagnosis of alzheimer's disease according to the nincds-adrda clinical criteria. 2. mild to moderate stage of alzheimer's disease according to mmse 18-26 inclusive. 3. modified hachinski ischemic scale equal to or below 4. 4. geriatric depression scale below or equal 7. 5. if anticholinesterasic treatment had been prescribed, the patient must undergo a 4 week wash out period before the baseline visit (visit 1). 6. if memantine treatment had been prescribed, the patient must undergo a 4 week wash out period before the baseline visit (visit 1). exclusion criteria: 1. clinical, laboratory or neuroimaging findings consistent with: * other primary degenerative dementia, (dementia with lewy bodies, frontotemporal dementia, huntington's disease, jacob-creutzfeld disease, down's syndrome, etc.) * other neurodegenerative condition (parkinson's disease, amyotrophic lateral sclerosis, etc.) * cerebrovascular disease (major infarct, one strategic or multiple lacunar infarcts, extensive white matter lesions \> one quarter of the total white matter) * other central nervous system diseases (severe head trauma, tumors, subdural haematoma or other space occupying processes, etc.) * seizure disorder * other infectious, metabolic or systemic diseases affecting central nervous system (syphilis, present hypothyroidism, present vitamin b12 or folate deficiency confirmed by current analyses not older than 1 month, serum electrolytes out of normal range, juvenile onset diabetes mellitus, etc.) 2. a current dsm-iv diagnosis of active major depression, schizophrenia or bipolar disorder. 3. chronic daily drug intake for a time period of ≥ 14 days or expected for ≥ 14 days: " * antidepressants, benzodiazepines, neuroleptics, major sedatives or other anti-inflammatory drugs including acetylic salicylic acid defined * antiepileptics * anticholinergics * nootropics (including ginkgo) * centrally active anti-hypertensive drugs (clonidine, alpha-methyl dopa, guanidine, guanfacine,) * opioid containing analgesics * anti-inflammatory agents, cortico-steroids or immunosuppressants * cimetidin as gastroprotective drug 4. severe thrombocytopenia defined as platelet counts \<100.000 per mm3. 5. coagulation disorders