Efficacy and Safety of Lornoxicam in Patients With Mild to Moderate Probable Alzheimer´s Disease.

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Multicentre Double-blind, Placebo-controlled, Randomised, Parallel-group Study to Evaluate the Efficacy and Safety of Lornoxicam in Patients With Mild to Moderate Probable Alzheimer´s Disease.

Conditions
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Alzheimer´s Disease

Intervention / Treatment
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* Drug: Lornoxicam
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women (non-childbearing potential) with a diagnosis of Alzheimer's Disease according to the NINCDS-ADRDA clinical criteria. Mild to moderate stage of Alzheimer's disease according to MMSE 18-26 inclusive. Modified Hachinski Ischemic Scale equal to or below 4. Geriatric Depression Scale below or equal 7. If anticholinesterasic treatment had been prescribed, the patient must undergo a 4 week wash out period before the baseline visit (visit 1). 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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lornoxicam<br>Lornoxicam (8 mg) tablets to be taken orally two times daily (BID) for a period of 6 months. | Drug: Lornoxicam<br>* Lornoxicam (8 mg) tablets to be taken orally two times daily (BID) for a period of 6 months.<br>* Other names: Telos;|
| Placebo Comparator: Placebo<br>Placebo (8 mg) tablets to be taken orally two times daily (BID) for a period of 6 months. | Drug: Placebo<br>* Placebo (8 mg) tablets to be taken orally two times daily (BID) for a period of 6 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive Performance - ADAS-cog+ | Alzheimer's disease Assessment Scale, Cognitive Subscale (15 item) Higher scores indicate cognitive impairment. All items are assessed by independent rater (psychologists). The score goes from 0 points (no cognitive impairment) to 95 points (maximum impairment in all 15 items). Primary Outcome Measure is the change from baseline ADAS-cog+ score to the score after 26 weeks (end of double blind). | 6 months double blind, 6 months open-label (optional) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Activities of Daily Living - ADCS-ADL; Behavioral/Psychiatric Symptoms - NPI |  | 6 months double-blind, 6 months open label (optional) |