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

Phase 2

Terminated

Conditions: Alzheimer´s Disease

Interventions: Drug: Placebo
Drug: Lornoxicam

Registration Number: NCT01117948

Lead Sponsor: JSW Lifesciences

Brief 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 219

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:

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.
1. 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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo (8 mg) tablets to be taken orally two times daily (BID) for a period of 6 months.
Lornoxicam	Lornoxicam	Lornoxicam (8 mg) tablets to be taken orally two times daily (BID) for a period of 6 months.

Primary Outcome Measures

Name	Time	Method
Cognitive Performance - ADAS-cog+	6 months double blind, 6 months open-label (optional)	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).

Secondary Outcome Measures