<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02249403</url>
  </required_header>
  <id_info>
    <org_study_id>506.203</org_study_id>
    <nct_id>NCT02249403</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Talsaclidine in Patients With Mild to Moderate Dementia of Alzheimer Type</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      The objective of this trial was to assess the dose-response relationship of symptomatic&#xD;
      efficacy of talsaclidine base on ADAScog and to assess safety and tolerability&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 1999</start_date>
  <primary_completion_date type="Actual">January 2000</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Alzheimer's Disease Assessment Scale cognitive part (ADAScog)</measure>
    <time_frame>Baseline, week 12</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in ADAScog (extension)</measure>
    <time_frame>Baseline, week 4, 8 and 12</time_frame>
    <description>measures cognitive capability</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in ADAScog (Total)</measure>
    <time_frame>Baseline, week 4, 8 and 12</time_frame>
    <description>Defined as ADAScog + ADAScog (Extension)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in mini mental state (MMS)</measure>
    <time_frame>Screening, week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in neuropsychiatric inventory (NPI)</measure>
    <time_frame>Baseline, week 12</time_frame>
    <description>measures behavioural symptoms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Hamilton Depression Rating Scale</measure>
    <time_frame>Screening, week 12</time_frame>
    <description>measures depressive mood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in instrumental activity of daily living (IADL)</measure>
    <time_frame>Baseline, week 12</time_frame>
    <description>measures functional performance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in living status rated on a 6-point verbal rating scale</measure>
    <time_frame>Baseline, week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in clinician's global impression rated with Alzheimer's Disease cooperative Study - Clinical Global Impression of Change (ADCS-CGIC)</measure>
    <time_frame>Baseline, week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">362</enrollment>
  <condition>Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>Talsaclidine, 6 mg tid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Talsaclidine, 12 mg tid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Talsaclidine, 24 mg tid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Talsaclidine, 36 mg tid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Talsaclidine, 36 mg bid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Talsaclidine 6 mg</intervention_name>
    <arm_group_label>Talsaclidine, 6 mg tid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Talsaclidine 12 mg</intervention_name>
    <arm_group_label>Talsaclidine, 12 mg tid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Talsaclidine 24 mg</intervention_name>
    <arm_group_label>Talsaclidine, 24 mg tid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Talsaclidine 36 mg</intervention_name>
    <arm_group_label>Talsaclidine, 36 mg bid</arm_group_label>
    <arm_group_label>Talsaclidine, 36 mg tid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Talsaclidine, 36 mg bid</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female patient, age: over 40 years (lower age if genetic Dementia of Alzheimer&#xD;
             Type (DAT) is documented. Patients over 85 years need to be in a clinically stable&#xD;
             state (investigator's judgement)&#xD;
&#xD;
          -  Patient's educational level is &gt; 4 years&#xD;
&#xD;
          -  Patient is able to understand the patient information and give informed consent&#xD;
&#xD;
          -  Patient has given written informed consent in accordance with Good Clinical Practice&#xD;
             and local legislation&#xD;
&#xD;
          -  Patient has a non-demented relative or care giver who is willing to support the&#xD;
             clinical trial; his/her written informed consent is optional&#xD;
&#xD;
          -  Body weight: within +/- 30% of normal weight (Broca index)&#xD;
&#xD;
          -  Diagnosis of DAT by the National Institute of Neurological and communicative&#xD;
             Disorders-Alzheimer's Disease and Related Disorder Association (NINCDS-ADRDA) criteria&#xD;
&#xD;
          -  MMS-score 10 - 24 inclusive&#xD;
&#xD;
          -  Rosen ischemia score is lower or equal to two&#xD;
&#xD;
          -  Patient is able to complete the trial examinations, to hear, speak, read and write in&#xD;
             a basic way and primary sensorial functions are intact&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any dementia of vascular genesis (excluded by Rosen ischemia score &gt; 2)&#xD;
&#xD;
          -  Magnetic Resonance Imaging (MRI) or Computer Tomogram (CT) (more recent than 12&#xD;
             months; if a MRI of CT recording is performed more than 12 months before study entry,&#xD;
             it must be repeated) findings make the diagnosis of DAT unlikely&#xD;
&#xD;
          -  Any stroke history&#xD;
&#xD;
          -  All secondary dementia (exclusion diagnosis defined by the NINCDS-ADRDA criteria) as a&#xD;
             late complication of:&#xD;
&#xD;
               -  Cranio-cerebral trauma&#xD;
&#xD;
               -  Intoxication (incl. history of alcohol and drug abuse)&#xD;
&#xD;
               -  Cerebral infections (e.g. neurosyphilis)&#xD;
&#xD;
               -  Thyroid dysfunction&#xD;
&#xD;
          -  Cerebral dysfunction due to metabolic disorders (e.g. unstable thyroid dysfunction, or&#xD;
             unstable insulin-dependent diabetes mellitus with hypo-/hyper-glycemic episodes)&#xD;
&#xD;
          -  Deficiency of vitamin B12 or folic acid as a reason of dementia&#xD;
&#xD;
          -  Brain tumour (A patient with an incidental tumour found on CT not felt to be&#xD;
             clinically relevant may be included, i.e.: meningioma)&#xD;
&#xD;
          -  Down's syndrome, Parkinsonism, Huntington's chorea&#xD;
&#xD;
          -  Multiple sclerosis&#xD;
&#xD;
          -  Major depression defined by the Hamilton Depression Rating Scale (HAMD) 17 item scale&#xD;
             (≥ 16)&#xD;
&#xD;
          -  Depressive pseudo dementia&#xD;
&#xD;
          -  Mental retardation&#xD;
&#xD;
          -  Hydrocephalus&#xD;
&#xD;
          -  Epilepsy&#xD;
&#xD;
          -  Endogenous psychoses (schizophrenia)&#xD;
&#xD;
          -  Untreated or non-compensated hypertension (Blood Pressure systolic &gt; 180 and/or&#xD;
             diastolic &gt; 110 mmHg)&#xD;
&#xD;
          -  Hypertension being treated with reserpine, clonidine or β-blockers (these cases have&#xD;
             to be adjusted to therapy with e.g. calcium antagonists 4 weeks before start of&#xD;
             treatment)&#xD;
&#xD;
          -  Severe heart failure (NYHA: III and IV)&#xD;
&#xD;
          -  Arrhythmias (Lown: II-IV, Electrocardiogram &gt; 30 ventricular extrasystoles/hour,&#xD;
             multifocal or multiform and repetitive forms of ventricular extrasystoles)&#xD;
&#xD;
          -  Bronchial asthma with phases of exacerbation or inducible by aspirin or other&#xD;
             Nonsteroidal anti-inflammatory drugs&#xD;
&#xD;
          -  Severe diabetes mellitus: insulin dependent and not stabilised (patient with an HbA1c&#xD;
             in normal range, clinically stable diabetes and any case of insulin dose ≤ 0.5&#xD;
             UI/kg/day may be included), or other metabolic diseases&#xD;
&#xD;
          -  Renal insufficiency: calculated creatinine clearance is less than 60 ml/min&#xD;
&#xD;
          -  Acute hepatic disorder (liver enzymes above 50 % upper normal limit)&#xD;
&#xD;
          -  Chronic hepatitis within the last two years (positive hepatitis titer, Hepatitis A&#xD;
             Virus, Hepatitis B Virus, Hepatitis C Virus, cytomegalovirus, Epstein-Barr virus or&#xD;
             abnormal immunological values (positive immunoglobulin M(IgM)/IgG) are allowed if all&#xD;
             liver enzymes are within the normal range)&#xD;
&#xD;
          -  Recent history of liver disease (2 years) including drug intoxication (e.g. narcotics,&#xD;
             cytostatics etc.)&#xD;
&#xD;
          -  Patients with obvious symptoms of dehydration&#xD;
&#xD;
          -  History of drug or alcohol abuse or dependence on other hepatotoxic agents (if a&#xD;
             patient is permanently hospitalised and a drug screen performed at the beginning of&#xD;
             hospitalisation, no additional drug screen is necessary)&#xD;
&#xD;
          -  Neoplasm currently active or likely to recur (except basal cell carcinoma)&#xD;
&#xD;
          -  Participation in another clinical trial within the last four weeks and re-entering&#xD;
             from this or a previous talsaclidine trial&#xD;
&#xD;
          -  Pregnant and lactating woman, woman with childbearing potential not using an approved&#xD;
             method of contraception&#xD;
&#xD;
          -  Insufficient compliance: in the investigator's opinion the patient or family is unable&#xD;
             to comply with the protocol requirements&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 23, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>September 25, 2014</last_update_submitted>
  <last_update_submitted_qc>September 25, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 26, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
    <mesh_term>Dementia</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02249403
org study id: 506.203
nct id: NCT02249403
lead sponsor: 
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
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Change in Alzheimer's Disease Assessment Scale cognitive part (ADAScog)
time frame: Baseline, week 12
measure: Change in ADAScog (extension)
time frame: Baseline, week 4, 8 and 12
description: measures cognitive capability
measure: Change in ADAScog (Total)
time frame: Baseline, week 4, 8 and 12
description: Defined as ADAScog + ADAScog (Extension)
measure: Change in mini mental state (MMS)
time frame: Screening, week 12
measure: Change in neuropsychiatric inventory (NPI)
time frame: Baseline, week 12
description: measures behavioural symptoms
measure: Change in Hamilton Depression Rating Scale
time frame: Screening, week 12
description: measures depressive mood
measure: Change in instrumental activity of daily living (IADL)
time frame: Baseline, week 12
description: measures functional performance
measure: Change in living status rated on a 6-point verbal rating scale
time frame: Baseline, week 12
measure: 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
measure: Number of patients with adverse events
time frame: up to 12 months
arm group label: Talsaclidine, 6 mg tid
arm group type: Experimental
arm group label: Talsaclidine, 12 mg tid
arm group type: Experimental
arm group label: Talsaclidine, 24 mg tid
arm group type: Experimental
arm group label: Talsaclidine, 36 mg tid
arm group type: Experimental
arm group label: Talsaclidine, 36 mg bid
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Talsaclidine 6 mg
arm group label: Talsaclidine, 6 mg tid
intervention type: Drug
intervention name: Talsaclidine 12 mg
arm group label: Talsaclidine, 12 mg tid
intervention type: Drug
intervention name: Talsaclidine 24 mg
arm group label: Talsaclidine, 24 mg tid
intervention type: Drug
intervention name: Talsaclidine 36 mg
arm group label: Talsaclidine, 36 mg bid
arm group label: Talsaclidine, 36 mg tid
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
arm group label: Talsaclidine, 36 mg bid
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Alzheimer Disease
mesh term: Dementia