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

Boehringer Ingelheim

Status and phase: Completed; Phase 2

Conditions: Alzheimer Disease

Treatments: Drug: Talsaclidine 6 mg; Drug: Talsaclidine 12 mg; Drug: Talsaclidine 24 mg; Drug: Placebo; Drug: Talsaclidine 36 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT02249403

506.203

Details and patient eligibility

About

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

Enrollment: 362 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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362 participants in 6 patient groups, including a placebo group

Talsaclidine, 6 mg tid

Experimental group

Treatment:

Drug: Talsaclidine 6 mg

Talsaclidine, 12 mg tid

Experimental group

Treatment:

Drug: Talsaclidine 12 mg

Talsaclidine, 24 mg tid

Experimental group

Treatment:

Drug: Talsaclidine 24 mg

Talsaclidine, 36 mg tid

Experimental group

Treatment:

Drug: Talsaclidine 36 mg

Talsaclidine, 36 mg bid

Experimental group

Treatment:

Drug: Talsaclidine 36 mg

Drug: Placebo

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo