A randomised, double-blind, placebo-controlled study to evaluate the safety and efficacy of two different doses of phenserine-tartrate in patients with probable mild to moderate Alzheimer’s disease
- Conditions
- Alzheimer's Disease is caused by a loss of nerve cells in the brain, particularly in the areas associated with memory and learning. The onset of Alzheimer's also affects the levels of a certain neurotransmitter in the brain.
- Registration Number
- EUCTR2004-000089-11-AT
- Lead Sponsor
- Axonyx Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 560
•Males of at least 50 years of age;
•Females of at least 50 years of age, who are either at least 2 years post-menopausal or surgically sterile;
•Probable Alzheimer’s disease consistent with National Institute of Neurological and Communicative Diseases and Stroke / Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria;
•Have had a computed tomography (CT) or magnetic resonance imaging (MRI) brain scan within the 12 months prior to inclusion in the study that is indicative of probable Alzheimer’s disease;
•A Mini-Mental State Examination (MMSE) score of between 12 and 24 (inclusive) at Visit 1 (screening);
•A modified Hachinsky Ischemic Scale (mHIS) score equal to or below 4 at Visit 1 (screening);
•Reliable caregiver available, and if not living in the same household, caregiver sees patient at least 4 times a week or a total of 15 to 20 hours per week;
•Patients who do not need continuous nursing care and who are either living at home or in an institutional setting;
•General health status acceptable for participation in a 6 month clinical study;
•Is capable of understanding and has given written informed consent [or this has been provided by their acceptable representative (according to local requirements)] and a separate caregiver responsibilities and consent form has also been signed by the patient’s caregiver;
•Agrees to comply with protocol requirements.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
General
•Failure to perform or comply with screening or baseline examinations;
•Hospitalisation (except for study purposes or due to social reasons, e.g. hospitalisation to unburden the caregiver);
•Change of concomitant medication 4 weeks prior to screening or during screening period;
•Participation in another therapeutic clinical study within the 3 months before Visit 2 (baseline);
•Inability to swallow tablets.
Medical
•Vitamin B12 or folate deficiency unless treated in which case treatment needs to have been stable for 3 months before study entry;
•Hypothyroidism, defined as any thyroid-stimulating hormone elevation. Corrected hypothyroidism is allowed provided treatment has been stable for 3 months before study entry;
•Juvenile onset diabetes mellitus;
•Adult onset diabetes mellitus insufficiently controlled [Haemoglobin A1c (HbA1c) > 8%];
•A malignancy within the last 5 years;
•HIV infection;
•Any history of hepatic insufficiency or abnormal liver enzymes;
•Renal insufficiency with abnormal serum creatinine outside the age appropriate normal range;
•Serum electrolytes (sodium, potassium, magnesium) outside the age appropriate normal range;
•Clinically significant abnormal laboratory values outside the age appropriate normal range;
•Hypersensitivity to cholinergic drugs;
•Uncontrolled asthma.
Cardiovascular
•Myocardial infarction or unstable angina within the 6 months prior to Visit 1 (screening);
•History of more than one myocardial infarction during the last 5 years;
•Cardiomyopathy;
•Myocarditis;
•Severe hypotension;
•Severe hypertension requiring treatment with more than 2 drugs;
•Bradycardia (frequency of heart beat < 50/minute);
•Tachycardia (frequency of heart beat > 90/minute);
•Presence of AV block (type II / Mobitz II and type III);
•Congenital long QT syndrome;
•Sinus node dysfunction;
•Prolonged QTcB-interval (males > 450 msec; females > 470 msec);
•Presence of U wave.
Psychiatric
•Axis I diagnosis within 1 year prior to study entry;
•Previous diagnosis of bipolar affective disorder or schizophrenia;
•Current alcohol or substance abuse or dependence;
•Metabolic or toxic encephalopathy or dementia due to a general medical condition;
•Geriatric Depression Score (GDS) > 5 at Visit 1 (screening).
Neurological
•Stroke within the 6 months prior to Visit 1 (screening) or concomitant with onset of dementia;
•Tumours, subdural haematoma or other space-occupying processes on CT/MRI;
•Head trauma with loss of consciousness within 1 year of the onset of dementia;
•Head trauma with loss of consciousness concurrent with the onset of dementia;
•Onset of dementia within 1 year following cardiac arrest, surgery with general anaesthetic or resuscitation;
•Degenerative central nervous system conditions e.g. Huntington’s disease (Huntington’s chorea), Creutzfeld-Jakob disease, Parkinson’s disease, etc.;
•Genetic cognitive impairment e.g. Trisomy 21 (Down’s syndrome);
•Wernicke’s encephalopathy;
•Acute or chronic central nervous system infection including tertiary syphilis;
•Epilepsy.
Previous Medication
Has previously received:
•Any acetylcholinesterase inhibitor in the 3 months before study entry;
•Any experimental drug 3 months before Visit 2 (baseline);
•Nootropics 1 month before Visit 1 (screening);
•Benzodiazepines administered on a chronic basis;
•Antipsychotics (unless prescribed for sleep disturbances) in the 3 months preceding study entry. If prescribed for sleep disturbance, then these should be discontinued 2 weeks p
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Cognitive performance [Alzheimer's Disease Assessment Scale - Cognitive Items (ADAS-COG)];<br>Activities of daily living [Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)].;Secondary Objective: ADAS-COG+ [Modified Alzheimer's Disease Assessment Scale - Cognitive Items (ADAS-COG+)];<br>Global clinical impression of therapeutic effect [Clinician's Interview Based Impression of Change (CIBIC+)];<br>Behavioural / psychiatric symptoms [Neuropsychiatric Inventory (NPI)].;Primary end point(s): The following efficacy assessments will be conducted in this study:<br>•ADAS-COG / ADAS-COG+;<br>•ADCS-ADL;<br>•Clinician’s Interview Based Impression (CIBI+) comprising the Clinician’s Interview Based Impression of Disease Severity (CIBIS+) or the Clinician’s Interview based Impression of Change (CIBIC+);<br>•NPI.<br>
- Secondary Outcome Measures
Name Time Method