<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/NCT02251197</url>
  </required_header>
  <id_info>
    <org_study_id>599.3</org_study_id>
    <nct_id>NCT02251197</nct_id>
  </id_info>
  <brief_title>Safety and Tolerability of BIII 890 in Patients With Acute Ischemic Stroke</brief_title>
  <official_title>A Randomised, Double-blind, Placebo-controlled, Clinical Trial to Evaluate the Safety and Tolerability in 108 Patients (18 Per Dose Group) With Acute Ischemic Stroke After Intravenous Administration From 6 to 72 Hours of BIII 890, as Loading Dose Followed by Maintenance Dose, in Escalating Dose Panels From 87.5 mg up to 1495 mg (Total Dose)</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 study is to assess the safety, tolerability and pharmacokinetic&#xD;
      characteristics of BIII 890 after intravenous infusion in acute ischemic stroke patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2001</start_date>
  <primary_completion_date type="Actual">October 2002</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>Number of patients with adverse events</measure>
    <time_frame>up to 45 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically relevant findings in vital signs</measure>
    <time_frame>up to 30 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically relevant findings in electrocardiogram (ECG)</measure>
    <time_frame>up to 45 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinically relevant findings in laboratory evaluation</measure>
    <time_frame>up to 45 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum concentration in plasma</measure>
    <time_frame>up to 120 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach maximum concentration in plasma</measure>
    <time_frame>up to 120 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal elimination half-life</measure>
    <time_frame>up to 120 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal rate constant</measure>
    <time_frame>up to 120 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve</measure>
    <time_frame>up to 120 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean residence time</measure>
    <time_frame>up to 120 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma clearance</measure>
    <time_frame>up to 120 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution at steady state</measure>
    <time_frame>up to 120 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glutamate plasma concentrations</measure>
    <time_frame>up to 72 hours after start of infusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in modified Rankin Scale</measure>
    <time_frame>Baseline, day 30</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Barthel Index</measure>
    <time_frame>Day 30</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in NIH stroke scale</measure>
    <time_frame>Baseline, day 1, 3, 7 and 30</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">97</enrollment>
  <condition>Stroke</condition>
  <arm_group>
    <arm_group_label>BIII 890 CL</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>escalating doses</description>
  </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>BIII 890 CL</intervention_name>
    <arm_group_label>BIII 890 CL</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female patients aged 18 years or above&#xD;
&#xD;
          -  Patients with an acute onset of a focal neurological deficit secondary to a lesion&#xD;
             presumed to be ischemic in etiology involving the carotid and/or vertebrobasilar&#xD;
             artery territories&#xD;
&#xD;
          -  Onset of symptoms within 24 hours prior to initiation of administration of study drug.&#xD;
             If the patient has awakened from sleep with the deficit, the time of onset will be&#xD;
             considered as the last time he/she was normal&#xD;
&#xD;
          -  Stroke symptoms are to be present for at least 1 hour and are still present at&#xD;
             randomisation. Symptoms must be distinguishable from an episode of generalised&#xD;
             ischemia (i.e. syncope), seizure, migraine or hypoglycaemic disorder&#xD;
&#xD;
          -  Patient is willing to participate voluntarily and to sign a written patient informed&#xD;
             consent. Informed consent will be obtained from each Patient (or the subject's&#xD;
             representative or relatives, depending on local regulations) according to Good&#xD;
             Clinical Practice and regulatory and legal requirements of the participating country.&#xD;
             Patients who are unable to sign but who are able to understand the meaning of&#xD;
             participation in the study may give an oral witnessed informed consent. These patients&#xD;
             have to make clear undoubtfully that they are wiling to participate voluntarily and&#xD;
             must be able to understand an Explanation of the contents of the Information sheet&#xD;
&#xD;
          -  Patient's life expectancy is at least 30 days (investigator's judgement)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of only minor stroke symptoms as characterised by a NIH score of &lt; 4 at the&#xD;
             time of randomisation&#xD;
&#xD;
          -  Severe obtundation as defined by a NIH Stroke Scale score of ≥ 2 using the Level of&#xD;
             Consciousness category; including coma or severe stupor&#xD;
&#xD;
          -  Any patient with a concurrent, severe neurological disease&#xD;
&#xD;
               -  Dementia, multi-infarct dementia&#xD;
&#xD;
               -  Multiple sclerosis&#xD;
&#xD;
               -  Previous stroke with residual deficit (i.e. pre-stroke modified Rankin Scale&#xD;
                  (mRS) must be ≤ 1). Tomographic or clinical evidence of brain stem infarct, any&#xD;
                  intracranial haemorrhage, primary or metastatic brain tumour, meningioma, or&#xD;
                  other space occupying lesion (e.g., subdural or epidural haematoma)&#xD;
&#xD;
               -  Patient with history of seizure related or not to their stroke diagnosis, except&#xD;
                  seizure secondary to fever in the childhood&#xD;
&#xD;
          -  Any patients with a concurrent mental deficit (e.g., AXIS-I psychiatric disorders as&#xD;
             defined by the Diagnostic and Statistical Manual (DSM) IV criteria: schizophrenia,&#xD;
             mood disorders (mania or major depression), psychotic/delusional disorders, a recent&#xD;
             history (6 months) or current evidence of alcohol or recreational drug abuse&#xD;
&#xD;
          -  Baseline blood glucose values below 2.75 mmol/l (hypoglycaemia) or above 22.0 mmol/l&#xD;
             (hyperglycaemia)&#xD;
&#xD;
          -  Sustained supine hypertension during the baseline period, and prior to randomisation,&#xD;
             as defined as two readings 30 minutes apart with a systolic blood pressure ≥ 220 mmHg&#xD;
             and/or a diastolic blood pressure ≥ 120 mmHg; and/or clinical diagnosis of malignant&#xD;
             hypertensive crisis accompanied by other signs or symptoms (e.g. nausea, vomiting,&#xD;
             obtundation, etc.) or complications (e.g. papilledema, retinal haemorrhage, hematuria,&#xD;
             or congestive heart failure)&#xD;
&#xD;
          -  Patients with known history of orthostatic hypotension, fainting spells or blackouts.&#xD;
             Hypotension as defined by a systolic blood pressure ≤ 90 mmHg or a diastolic blood&#xD;
             pressure ≤ 50 mmHg&#xD;
&#xD;
          -  Patients currently on oral anticoagulants. A time window of at least two days should&#xD;
             be observed when such a treatment has been administered and stopped before the&#xD;
             beginning of the trial&#xD;
&#xD;
          -  Known history of a serious, advanced, unstable or terminal illness that in the opinion&#xD;
             of the clinical investigator may interfere with the trial by confounding the results&#xD;
             or pose an additional risk:&#xD;
&#xD;
               -  cardiogenic shock, congestive heart failure (NYHA Class III-IV), acute myocardial&#xD;
                  infarction or history of a myocardial infarction within the past three months,&#xD;
                  unstable angina&#xD;
&#xD;
               -  renal failure, severe hepatic disease, unstable gastrointestinal, pulmonary,&#xD;
                  metabolic, immunological, hormonal disorders&#xD;
&#xD;
               -  cancer (except local skin cancers, e.g.: basal or squamous carcinoma)&#xD;
&#xD;
               -  HIV+&#xD;
&#xD;
          -  Females who are lactating or pregnant (as determined by a pregnancy test during&#xD;
             screening) or of childbearing potential&#xD;
&#xD;
          -  Current or recent (within 3 months) participation in another investigational drug&#xD;
             protocol&#xD;
&#xD;
          -  Patient cannot be followed for 30 days (according to the judgement of the&#xD;
             investigator)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 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 25, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 29, 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 29, 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>Stroke</mesh_term>
    <mesh_term>Ischemic Stroke</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/NCT02251197
org study id: 599.3
nct id: NCT02251197
lead sponsor: 
The objective of this study is to assess the safety, tolerability and pharmacokinetic
      characteristics of BIII 890 after intravenous infusion in acute ischemic stroke patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Number of patients with adverse events
time frame: up to 45 days
measure: Number of patients with clinically relevant findings in vital signs
time frame: up to 30 days
measure: Number of patients with clinically relevant findings in electrocardiogram (ECG)
time frame: up to 45 days
measure: Number of patients with clinically relevant findings in laboratory evaluation
time frame: up to 45 days
measure: Maximum concentration in plasma
time frame: up to 120 hours after drug administration
measure: Time to reach maximum concentration in plasma
time frame: up to 120 hours after drug administration
measure: Terminal elimination half-life
time frame: up to 120 hours after drug administration
measure: Terminal rate constant
time frame: up to 120 hours after drug administration
measure: Area under the plasma concentration-time curve
time frame: up to 120 hours after drug administration
measure: Mean residence time
time frame: up to 120 hours after drug administration
measure: Plasma clearance
time frame: up to 120 hours after drug administration
measure: Volume of distribution at steady state
time frame: up to 120 hours after drug administration
measure: Glutamate plasma concentrations
time frame: up to 72 hours after start of infusion
measure: Change in modified Rankin Scale
time frame: Baseline, day 30
measure: Barthel Index
time frame: Day 30
measure: Change in NIH stroke scale
time frame: Baseline, day 1, 3, 7 and 30
arm group label: BIII 890 CL
arm group type: Experimental
description: escalating doses
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: BIII 890 CL
arm group label: BIII 890 CL
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Stroke
mesh term: Ischemic Stroke