A Randomised, Double-Blind, Placebo-Controlled Trialto Evaluate the Safety and Efficacy of Two DifferentDosages of Phenserine-tartrate in Patients with Mild toModerate Probable Alzheimer’s Disease -Phenserine/APP and Aß
- Conditions
- Alzheimer’s Disease is a chronic progressive illness leading to loss of cognitive and intellectual abilities such as memory function, judgement and abstract thinking.In addition to the cognitive deficits the patients experience loss of their ability to take care of instrumental activities of daily living, they are not able to meet the most common requirements of daily life and so they are loosing their independence, needing intensive health care in final stages of the disease.MedDRA version: 7.0Level: PrimClassification code 10001896
- Registration Number
- EUCTR2004-001187-52-LV
- Lead Sponsor
- Axonyx Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 150
• Signed informed consent by patient or the legally accepted representative prior to the
initiation of any study specific procedures
• Male or female patients of at least 50 years of age
• Probable Alzheimer’s Disease consistent with NINCDS-ADRDA criteria (Appendix 1).
• MRI or CT scan within the last 12 months prior to baseline; findings consistent with the
diagnosis of probable Alzheimer’s Disease
• Mini-Mental state examination score (MMSE) between 24 and 9 inclusive
• Modified Hachinsky ischemic score equal or below 4
• Female patients must be at least 2 years post-menopausal or surgically sterile
• Caregiver available, if not living in the same household, caregiver sees patient at least 4 times a week
• Patients living at home, old people’s home or an institutional setting without continuous
nursing care
• General health status acceptable for a participation in a 6 month clinical trial
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
• Violation of inclusion criteria not approved by clinical study director or study safety officer
• Failure to perform or to evaluate screening or baseline examinations
• Hospitalisation (except for study purposes or due to social reasons, e.g. hospitalisation to
unburden the caregiver) or change of concomitant medication 4 weeks prior to screening
or during screening period
• Participation in another therapeutic clinical trial 3 months before baseline
• Inability to swallow tablets
Medical
• Unsubstituted vitamin B12 or folate deficiency
• Serum electrolytes (sodium, potassium, magnesium) out of normal range
• Unsubstituted hypothyroidism with TSH > 6,00 µU/ml
• Juvenile onset diabetes mellitus
• Adult onset diabetes mellitus insufficiently controlled (HbA1c > 8 %)
• Renal insufficiency with serum creatinine > 2mg/dl
• Severe hypotension requiring treatment with more than 2 drugs
• Lab values seriously abnormal, and/or more than 2 lab values abnormal not approved by
clinical study director or study safety officer
• Hypersensitivity to cholinergic drugs
• Serious drug allergies
• Malignant tumours within the last 5 years
Cardiovascular
• Myocardial infarction or unstable angina within the last 6 months before screening
• History of more than 1 myocardial infarction during the last 5 years
• Cardiomyopathy
• Myocarditis
• Atrial fibrillation
• Severe hypotension requiring treatment with more than 2 drugs
• Severe hypertension requiring treatment with more than 2 drugs
• Bradycardia (frequency of heart beat < 50/min.)
• Tachycardia (frequency of heart beat > 90/min.)
• Presence of AV block (type II / Mobitz II and type III)
• Congenital long QT syndrome
• Sinus node dysfunction
• Prolonged QTcB-interval (males > 450 and females > 470 msec)
• QTcB dispersion > 100 msec
• Presence of U wave
Psychiatric
• Episode of major depression in medical history
• GDS score (15 item scale) > 5
• History or presence of schizophrenia
• Chronic intoxication or chronic substance use disorder with pharmaceuticals, drugs,
alcohol or industrial poisons
Neurological
• Stroke within 6 months before 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 before or concurrent with onset of
dementia
• Onset of dementia within 1 year following cardiac arrest, surgery with general anaesthesia
or resuscitation
• Degenerative CNS disease, e.g. M. Huntington, Jacob-Creutzfeld disease, Downs
syndrome
• Wernickes encephalopathy
• Acute or chronic CNS infection including tertiary syphilis
Previous Medication
• Acetylcholinesterase inhibitors 3 months before baseline
• Any experimental drug 3 months before enrolment
• Nootropics 1 month before screening
• Promethazine, thioridazine, chlorprothixene, flunitrazepam or nitrazepam not discontinued
2 weeks before screening
• Antipsychotics if not given for sleep disturbances
• Antidepressants, except stable treatment with SSRI´s for at least 3 months prior to
screening
Concomitant Medication
• Peripherally acting drugs with effects on cholinergic transmission
• Immunosuppresants
• Antiparkinsonian therapy
• Antiepileptics
• Centrally active anti-hypertensive drugs like clonidine, alpha methyl dopa, guanidine,
guanfacine or moxonidine
• Non-steroidal anti-inflammatory drugs 72 h before blood plasma or CSF sampling
• Cholesterol lowering drugs inhibiting HMG CoA reductase (simvastatin, pravastatin,
fluvasta
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate effects of Phenserine-tartrate on cognitive performance using a standardized psychometric test (Cognitive Performance - ADAS-cog) and to evaluate the drug effect on global function involving the caregiver (Global clinical impression of therapeutic effect- CIBIC+) in comparison with Placebo.<br><br><br>;Secondary Objective: Placebo controlled comparison of the efficacy of two different dosages of Phenserine-tartrate, 10mg BID and 15mg BID based on the following endpoints:<br>- Activity of daily living - ADCS<br>- Behavioural/psychiatric symptoms - NPI<br>Effect on Amyloid production -blood plasma and Cerebrospinal fluid (=CSF) concentration of soluble APP, Aß1-40 and Aß1-42;Primary end point(s): Placebo controlled comparison of the efficacy of two different dosages of Phenserine-tartrate, 10mg BID and 15mg BID based on the following endpoints:<br>• Cognitive Performance - ADAS-cog+<br>• Global clinical impression of therapeutic effect- CIBIC+
- Secondary Outcome Measures
Name Time Method