Alzheimer´s Disease
Conditions
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.
Interventions
DRUGLornoxicam
Lornoxicam (8 mg) tablets to be taken orally two times daily (BID) for a period of 6 months.
DRUGPlacebo
Placebo (8 mg) tablets to be taken orally two times daily (BID) for a period of 6 months.
Sponsors
JSW Lifesciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| Activities of Daily Living - ADCS-ADL; Behavioral/Psychiatric Symptoms - NPI | 6 months double-blind, 6 months open label (optional) |
Participant flow
Recruitment details
First patient in: 09 Nov 2009 Last patient out: 30 Apr 2011 Patients were recruited in Clinics and Outpatient Clinics
Pre-assignment details
Patients were excluded if they did not meet all inclusion/exclusion criteria or if the caregiver was not giving consent to participation in the trial
Participants by arm
| Arm | Count |
|---|---|
| Lornoxicam Lornoxicam (8 mg) tablets to be taken orally two times daily (BID) for a period of 6 months. | 111 |
| Placebo Placebo (8 mg) tablets to be taken orally two times daily (BID) for a period of 6 months. | 108 |
| Total | 219 |
Baseline characteristics
| Characteristic | Lornoxicam | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 101 Participants | 89 Participants | 190 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 19 Participants | 29 Participants |
| Age Continuous | 74.5 years STANDARD_DEVIATION 6.75 | 73.6 years STANDARD_DEVIATION 8.11 | 74.1 years STANDARD_DEVIATION 7.45 |
| Region of Enrollment Austria | 35 participants | 35 participants | 70 participants |
| Region of Enrollment Czech Republic | 37 participants | 41 participants | 78 participants |
| Region of Enrollment Germany | 11 participants | 11 participants | 22 participants |
| Region of Enrollment Slovakia | 28 participants | 21 participants | 49 participants |
| Sex: Female, Male Female | 69 Participants | 67 Participants | 136 Participants |
| Sex: Female, Male Male | 42 Participants | 41 Participants | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 111 | 0 / 108 |
| serious Total, serious adverse events | 11 / 111 | 2 / 108 |
Outcome results
Primary
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).
Time frame: 6 months double blind, 6 months open-label (optional)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lornoxicam | Cognitive Performance - ADAS-cog+ | -0.05 units on a scale | Standard Deviation 6.75 |
| Placebo | Cognitive Performance - ADAS-cog+ | -0.89 units on a scale | Standard Deviation 7.84 |
Secondary
Activities of Daily Living - ADCS-ADL; Behavioral/Psychiatric Symptoms - NPI
Time frame: 6 months double-blind, 6 months open label (optional)