Efficacy and Safety of Talsaclidine in Patients With Mild to Moderate Dementia of Alzheimer Type

NCT ID: NCT02249403

Last Updated: 2014-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 362 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-01-31

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

Conditions

Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Talsaclidine, 6 mg tid

Group Type: EXPERIMENTAL

Talsaclidine 6 mg

Intervention Type: DRUG

Talsaclidine, 12 mg tid

Group Type: EXPERIMENTAL

Talsaclidine 12 mg

Intervention Type: DRUG

Talsaclidine, 24 mg tid

Group Type: EXPERIMENTAL

Talsaclidine 24 mg

Intervention Type: DRUG

Talsaclidine, 36 mg tid

Group Type: EXPERIMENTAL

Talsaclidine 36 mg

Intervention Type: DRUG

Talsaclidine, 36 mg bid

Group Type: EXPERIMENTAL

Talsaclidine 36 mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Talsaclidine 6 mg

Intervention Type: DRUG

Talsaclidine 12 mg

Intervention Type: DRUG

Talsaclidine 24 mg

Intervention Type: DRUG

Talsaclidine 36 mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

506.203

Identifier Type: -

Identifier Source: org_study_id