Efficacy and Safety of Talsaclidine in Patients With Mild to Moderate Dementia of Alzheimer Type
Primary Purpose
Alzheimer Disease
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Talsaclidine 6 mg
Talsaclidine 12 mg
Talsaclidine 24 mg
Talsaclidine 36 mg
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer Disease
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Talsaclidine, 6 mg tid
Talsaclidine, 12 mg tid
Talsaclidine, 24 mg tid
Talsaclidine, 36 mg tid
Talsaclidine, 36 mg bid
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Change in Alzheimer's Disease Assessment Scale cognitive part (ADAScog)
Secondary Outcome Measures
Change in ADAScog (extension)
measures cognitive capability
Change in ADAScog (Total)
Defined as ADAScog + ADAScog (Extension)
Change in mini mental state (MMS)
Change in neuropsychiatric inventory (NPI)
measures behavioural symptoms
Change in Hamilton Depression Rating Scale
measures depressive mood
Change in instrumental activity of daily living (IADL)
measures functional performance
Change in living status rated on a 6-point verbal rating scale
Change in clinician's global impression rated with Alzheimer's Disease cooperative Study - Clinical Global Impression of Change (ADCS-CGIC)
Number of patients with adverse events
Full Information
NCT ID
NCT02249403
First Posted
September 23, 2014
Last Updated
September 25, 2014
Sponsor
Boehringer Ingelheim
1. Study Identification
Unique Protocol Identification Number
NCT02249403
Brief Title
Efficacy and Safety of Talsaclidine in Patients With Mild to Moderate Dementia of Alzheimer Type
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
January 1999 (undefined)
Primary Completion Date
January 2000 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
362 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Talsaclidine, 6 mg tid
Arm Type
Experimental
Arm Title
Talsaclidine, 12 mg tid
Arm Type
Experimental
Arm Title
Talsaclidine, 24 mg tid
Arm Type
Experimental
Arm Title
Talsaclidine, 36 mg tid
Arm Type
Experimental
Arm Title
Talsaclidine, 36 mg bid
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Talsaclidine 6 mg
Intervention Type
Drug
Intervention Name(s)
Talsaclidine 12 mg
Intervention Type
Drug
Intervention Name(s)
Talsaclidine 24 mg
Intervention Type
Drug
Intervention Name(s)
Talsaclidine 36 mg
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Change in Alzheimer's Disease Assessment Scale cognitive part (ADAScog)
Time Frame
Baseline, week 12
Secondary Outcome Measure Information:
Title
Change in ADAScog (extension)
Description
measures cognitive capability
Time Frame
Baseline, week 4, 8 and 12
Title
Change in ADAScog (Total)
Description
Defined as ADAScog + ADAScog (Extension)
Time Frame
Baseline, week 4, 8 and 12
Title
Change in mini mental state (MMS)
Time Frame
Screening, week 12
Title
Change in neuropsychiatric inventory (NPI)
Description
measures behavioural symptoms
Time Frame
Baseline, week 12
Title
Change in Hamilton Depression Rating Scale
Description
measures depressive mood
Time Frame
Screening, week 12
Title
Change in instrumental activity of daily living (IADL)
Description
measures functional performance
Time Frame
Baseline, week 12
Title
Change in living status rated on a 6-point verbal rating scale
Time Frame
Baseline, week 12
Title
Change in clinician's global impression rated with Alzheimer's Disease cooperative Study - Clinical Global Impression of Change (ADCS-CGIC)
Time Frame
Baseline, week 12
Title
Number of patients with adverse events
Time Frame
up to 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
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
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com
Description
Related Info
Learn more about this trial
Efficacy and Safety of Talsaclidine in Patients With Mild to Moderate Dementia of Alzheimer Type
We'll reach out to this number within 24 hrs