Alzheimer’s Disease (AD) is the most common disease leading to dementia and it affects approximately 4 to 8% of the population aged above 65 years. The disease incidence is closely correlated with increasing age and it doubles within every 5 years time period of increasing age.Optimal treatment would slow down or even stop the progression of disease, to maintain the independence of the patient by improving his every-day competency.
Conditions
Interventions
Product Name: phenserine tartrate
Pharmaceutical Form: Tablet
Other descriptive name: phenserine tartrate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmac
Sponsors
Axonyx Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria • 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 • MRI or CT scan within the last 12 months prior to baseline shoud exclude other aetiologies than AD to the patients dementia symptoms (e.g stroke). • Mini-Mental state examination score (MMSE) between 20 and 26 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 • Subjects to be selected for participating in the study must undergo PET studies with [18F]-fluorodeoxy-glucose (FDG) as a part of the screening and show changes in cerebral metabolism consistent with AD 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
Exclusion criteria
Exclusion criteria: Exclusion criteria General • 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 >2 mg/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 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*) • History or presence of schizophrenia • Chronic intoxication or chronic substance use disorder with pharmaceuticals, drugs, alcohol or industrial poisons *) A major depression has to be excluded by the investigator. This will be done by appropriate scales or methods, if considered necessary, and documented in source data. 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 if 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this phase IIb pilot study is to assess the safety of PT treatment and the effects of this drug on cognitive performance, brain metabolic activity as well as on APP metabolism in comparison to Placebo/active drug treatment in patients suffering from Alzheimer’s Disease. Special attention will be focused on PT effects on brain amyloid load and brain glucose metabolism. Primary: Placebo-controlled comparison of the efficacy of Phenserine-tartrate (PT,15 mg BID) based on the following end-points: • Cerebral Glucose metabolism using Positron Emission Tomography (FDG) • Brain-Amyloid Load measured by Positron Emission Tomography ([11C]- PIB) • CSF sAPP, Aß1-40, Aß1-42; total Tau, phospho-Tau • Blood sAPP ;Secondary Objective: Secondary: Placebo-controlled comparison of the efficacy of PT, 15 mg BID based on the following parameters: • Cognitive Performance: ADAS-cog+ • Episodic memory: Kungsholmen Word Recall and Word Recognition Test • Visual spatial ability : Clock Test-perception and drawing • Attention: Digit Symbol Substitution Test, Trail Making Test A and B • Measurement of Phenserine concentrations in CSF and plasma • Measurement of Acetylcholinesterase and Butyryl-cholinesterase in plasma, red blood cells and CSF Placebo/active drug-controlled comparison of the safety of PT, 15 mg BID ;Primary end point(s): Primary: Placebo-controlled comparison of the efficacy of Phenserine-tartrate (PT,15 mg BID) based on the following end-points: • Cerebral Glucose metabolism using Positron Emission Tomography (FDG) • Brain-Amyloid Load measured by Positron Emission Tomography ([11C]- PIB) • CSF sAPP, Aß1-40, Aß1-42; total Tau, phospho-Tau • Blood sAPP | — |
Countries
Sweden
Outcome results
None listed