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

Efficacy and Safety of 6, 12, 24, and 36 mg Tid po and 36 mg Bid po Talsaclidine (Free Base) for 12 Weeks in a Double-blind, Randomised, Placebo-controlled Parallel Group Comparison in Patients With Mild to Moderate Dementia of Alzheimer Type

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

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Placebo; Drug: Talsaclidine 6 mg; Drug: Talsaclidine 12 mg; Drug: Talsaclidine 24 mg; Drug: Talsaclidine 36 mg

• Study Type: Interventional
• Enrollment (Actual): 362
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: Talsaclidine, 6 mg tid	Drug: Talsaclidine 6 mg
Experimental: Talsaclidine, 12 mg tid	Drug: Talsaclidine 12 mg
Experimental: Talsaclidine, 24 mg tid	Drug: Talsaclidine 24 mg
Experimental: Talsaclidine, 36 mg tid	Drug: Talsaclidine 36 mg
Experimental: Talsaclidine, 36 mg bid	Drug: Placebo; Drug: Talsaclidine 36 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Alzheimer's Disease Assessment Scale cognitive part (ADAScog)	Baseline, week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mini mental state (MMS)		Screening, 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
Change in ADAScog (extension)	measures cognitive capability	Baseline, week 4, 8 and 12
Change in ADAScog (Total)	Defined as ADAScog + ADAScog (Extension)	Baseline, week 4, 8 and 12
Change in neuropsychiatric inventory (NPI)	measures behavioural symptoms	Baseline, week 12
Change in Hamilton Depression Rating Scale	measures depressive mood	Screening, week 12
Change in instrumental activity of daily living (IADL)	measures functional performance	Baseline, week 12
Change in living status rated on a 6-point verbal rating scale		Baseline, week 12
Number of patients with adverse events		up to 12 months

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: January 1, 1999
• Primary Completion (Actual): January 1, 2000

Study Registration Dates

• First Submitted: September 23, 2014
• First Submitted That Met QC Criteria: September 23, 2014
• First Posted (Estimate): September 25, 2014

Study Record Updates

• Last Update Posted (Estimate): September 26, 2014
• Last Update Submitted That Met QC Criteria: September 25, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Tauopathies; Dementia; Alzheimer Disease
• Other Study ID Numbers: 506.203