Alzheimer Disease
Conditions
Brief 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
Interventions
DRUGTalsaclidine 6 mg
DRUGTalsaclidine 12 mg
DRUGTalsaclidine 24 mg
DRUGTalsaclidine 36 mg
DRUGPlacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Alzheimer's Disease Assessment Scale cognitive part (ADAScog) | Baseline, week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in ADAScog (Total) | Baseline, week 4, 8 and 12 | Defined as ADAScog + ADAScog (Extension) |
| Change in mini mental state (MMS) | Screening, week 12 | — |
| Change in neuropsychiatric inventory (NPI) | Baseline, week 12 | measures behavioural symptoms |
| Change in Hamilton Depression Rating Scale | Screening, week 12 | measures depressive mood |
| Change in ADAScog (extension) | Baseline, week 4, 8 and 12 | measures cognitive capability |
| Change in living status rated on a 6-point verbal rating scale | Baseline, week 12 | — |
| Change in clinician's global impression rated with Alzheimer's Disease cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) | Baseline, week 12 | — |
| Number of patients with adverse events | up to 12 months | — |
| Change in instrumental activity of daily living (IADL) | Baseline, week 12 | measures functional performance |
Outcome results
None listed