efficacy and safety of talsaclidine in patients with mild to moderate dementia of alzheimer type

Conditions: Alzheimer Disease

Summary: the objective of this trial was to assess the dose-response relationship of symptomatic efficacy of talsaclidine base on adascog and to assess safety and tolerability


Eligibility criteria:
inclusion criteria: * male or female patient, age: over 40 years (lower age if genetic dementia of alzheimer type (dat) is documented. patients over 85 years need to be in a clinically stable state (investigator's judgement) * patient's educational level is \> 4 years * patient is able to understand the patient information and give informed consent * patient has given written informed consent in accordance with good clinical practice and local legislation * patient has a non-demented relative or care giver who is willing to support the clinical trial; his/her written informed consent is optional * body weight: within +/- 30% of normal weight (broca index) * diagnosis of dat by the national institute of neurological and communicative disorders-alzheimer's disease and related disorder association (nincds-adrda) criteria * mms-score 10 - 24 inclusive * rosen ischemia score is lower or equal to two * patient is able to complete the trial examinations, to hear, speak, read and write in a basic way and primary sensorial functions are intact exclusion criteria: * any dementia of vascular genesis (excluded by rosen ischemia score \> 2) * magnetic resonance imaging (mri) or computer tomogram (ct) (more recent than 12 months; if a mri of ct recording is performed more than 12 months before study entry, it must be repeated) findings make the diagnosis of dat unlikely * any stroke history * all secondary dementia (exclusion diagnosis defined by the nincds-adrda criteria) as a late complication of: * cranio-cerebral trauma * intoxication (incl. history of alcohol and drug abuse) * cerebral infections (e.g. neurosyphilis) * thyroid dysfunction * cerebral dysfunction due to metabolic disorders (e.g. unstable thyroid dysfunction, or unstable insulin-dependent diabetes mellitus with hypo-/hyper-glycemic episodes) * deficiency of vitamin b12 or folic acid as a reason of dementia * brain tumour (a patient with an incidental tumour found on ct not felt to be clinically relevant may be included, i.e.: meningioma) * down's syndrome, parkinsonism, huntington's chorea * multiple sclerosis * major depression defined by the hamilton depression rating scale (hamd) 17 item scale (≥ 16) * depressive pseudo dementia * mental retardation * hydrocephalus * epilepsy * endogenous psychoses (schizophrenia) * untreated or non-compensated hypertension (blood pressure systolic \> 180 and/or diastolic \> 110 mmhg) * hypertension being treated with reserpine, clonidine or β-blockers (these cases have to be adjusted to therapy with e.g. calcium antagonists 4 weeks before start of treatment) * severe heart failure (nyha: iii and iv) * arrhythmias (lown: ii-iv, electrocardiogram \> 30 ventricular extrasystoles/hour, multifocal or multiform and repetitive forms of ventricular extrasystoles) * bronchial asthma with phases of exacerbation or inducible by aspirin or other nonsteroidal anti-inflammatory drugs * severe diabetes mellitus: insulin dependent and not stabilised (patient with an hba1c in normal range, clinically stable diabetes and any case of insulin dose ≤ 0.5 ui/kg/day may be included), or other metabolic diseases * renal insufficiency: calculated creatinine clearance is less than 60 ml/min * acute hepatic disorder (liver enzymes above 50 % upper normal limit) * chronic hepatitis within the last two years (positive hepatitis titer, hepatitis a virus, hepatitis b virus, hepatitis c virus, cytomegalovirus, epstein-barr virus or abnormal immunological values (positive immunoglobulin m(igm)/igg) are allowed if all liver enzymes are within the normal range) * recent history of liver disease (2 years) including drug intoxication (e.g. narcotics, cytostatics etc.) * patients with obvious symptoms of dehydration * history of drug or alcohol abuse or dependence on other hepatotoxic agents (if a patient is permanently hospitalised and a drug screen performed at the beginning of hospitalisation, no additional drug screen is necessary) * neoplasm currently active or likely to recur (except basal cell carcinoma) * participation in another clinical trial within the last four weeks and re-entering from this or a previous talsaclidine trial * pregnant and lactating woman, woman with childbearing potential not using an approved method of contraception * insufficient compliance: in the investigator's opinion the patient or family is unable to comply with the protocol requirements