E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of Lornoxicam (8 mg, BID) administered for 6 months versus matched placebo, based on the end-point: "Cognitive performance – ADAS-cog+". |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of Lornoxicam (8 mg, BID) administered for 6 months versus matched placebo, based on the end-points: "Activities of daily living – ADCS-ADL"; "Behavioural / psychiatric symptoms – NPI".
To evaluate the safety of Lornoxicam (8 mg, BID) administered for 6 months versus matched placebo.
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 performed. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men and women (non-childbearing potential) with a diagnosis of Alzheimer’s disease according to the NINCDS-ADRDA clinical criteria. 2. Age 50 - 85 years inclusive 3. MRI or CT assessment within 12 months before baseline corroborating the clinical diagnosis and excluding other potential causes of dementia, especially cerebrovascular lesions (see exclusion criterion 3). 4. Mild to moderate stage of Alzheimer’s disease according to MMSE 18-26 inclusive. 5. Previous decline of cognition for more than 6 months. 6. Modified Hachinski Ischemic Scale equal to or below 4. 7. Geriatric Depression Scale below or equal 7. 8. Female patients must be either surgically sterilized or at least 1 year postmenopausal. 9. A caregiver is available and is living in the same household, or interacts regularly with the patient or patients living at home or old people’s home. 10. General health status acceptable for a participation in a 12 month clinical trial. 11. Ability to swallow tablets. 12. If anticholinesterasic treatment had been prescribed, the patient must undergo a 4 week wash out period before the baseline visit (visit 1). 13. If Memantine treatment had been prescribed, the patient must undergo a 4 week wash out period before the baseline visit (visit 1). 14. Stable pharmacological treatment response of any other chronic condition for at least one month prior to screening. 15. No daily-regular/chronic intake of medications acting on central nervous system, immunosupresants, steroids or non-steroid anti-inflammatory agents except the following allowed treatments: - SSRIs as antidepressants if they are administered at a stable and well tolerated dose for two months prior to baseline evaluation - Drugs at a stable and well tolerated dose to symptomatic treatment of mild behavioural disorder, sleep onset-insomnia or mild depressive mood: Zolpidem max 10 mg/day Trazodon max 150 mg/day Prothipendyl-Hydrochloridmonohydrat max 80 mg/day Mirtazapin max 30 mg/day - Acetylsalicylic acid max 100 mg/day. 16. Signed informed consent by caregiver and patient (or legal guardian if applicable) prior to the initiation of any study specific procedure. |
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E.4 | Principal exclusion criteria |
1. Failure to perform screening examinations. 2. Change of chronic concomitant medication during screening period. 3. 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.) 4. A current DSM-IV diagnosis of active major depression, schizophrenia or bipolar disorder. 5. Clinically significant, advanced or unstable disease that may interfere with primary or secondary variable evaluations, may bias the assessment of the clinical or mental status of the patient or put the patient at special risk, such as: - chronic liver disease, liver function test abnormalities or other signs of hepatic insufficiency (ALT, AST, Gamma GT, Alkaline Phosphatase > 2.5 ULN) - respiratory insufficiency - renal insufficiency (serum creatinine > 2 mg/dl or creatinine clearance ≤ 45 ml/min according to Cockgroft-Gault formula). - gastro-intenstinal bleeding, cerebrovascular bleeding or other conditions with bleeding disorders - active peptic or duodenal ulceration or with a history of recurrent peptic or duodenal ulceration - hypersensitive reactions (asthma, rhinitis, angioedema or urticaria) to NSAIDs including Lornoxicam - heart disease (atrial fibrillation, myocardial infarction, unstable angina, history or clinical evidence of heart failure, cardiomyopathy within 6 months before screening) - bradycardia (heart rate < 50/min.) or tachycardia (heart rate > 95/min.) - uncontrolled hypertension (defined as a repeatedly elevated blood pressure exceeding 140 over 90 mmHg - a systolic pressure above 140 with a diastolic pressure above 90) - hypertension or hypotension requiring treatment with more than 3 drugs - AV block (type II / Mobitz II and type III), congenital long QT syndrome, sinus node dysfunction or prolonged QTcB-interval (males > 450 and females > 470 msec) - uncontrolled diabetes, defined by HbA1c > 8.5 - malignant tumors within the last 5 years except skin malignancies (other than melanoma) or indolent prostate cancer - metastases 6. Disability that may prevent the subject from completing all study requirements (e.g. blindness, deafness, severe language difficulty, etc.) 7. Women who are fertile and of child bearing potential. 8. 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 (except those defined as allowed in the inclusion criterion number 15) - 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 9. Suspected or known drug or alcohol abuse, i.e. more than approximately 60 g alcohol (approximately 1 liter of beer or 0.5 liter of wine) per day indicated by elevated MCV significantly above normal value at screening. 10. Suspected or known allergy to any components of the study treatments. 11. Severe thrombocytopenia, defined as platelet counts < 100.000 per mm³. 12. Enrolment in another investigational study or intake of investigational medicinal product within the previous 3 months. 13. Any condition which in the opinion of the investigator makes the patient unsuitable for inclusion. 14. Coagulation disorders |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the effect of Lornoxicam on cognitive symptoms of Alzheimer's Disease as assessed by the ADAS cog+ questionnaire. Shown as an higher improvement of the ADAS cog+ performance of the verum group, compared to the placebo group. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |