Safety and Tolerability of BIII 890 in Patients With Acute Ischemic Stroke
Primary Purpose
Stroke
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
BIII 890 CL
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Stroke
Eligibility Criteria
Inclusion Criteria:
- Male or female patients aged 18 years or above
- Patients with an acute onset of a focal neurological deficit secondary to a lesion presumed to be ischemic in etiology involving the carotid and/or vertebrobasilar artery territories
- Onset of symptoms within 24 hours prior to initiation of administration of study drug. If the patient has awakened from sleep with the deficit, the time of onset will be considered as the last time he/she was normal
- Stroke symptoms are to be present for at least 1 hour and are still present at randomisation. Symptoms must be distinguishable from an episode of generalised ischemia (i.e. syncope), seizure, migraine or hypoglycaemic disorder
- Patient is willing to participate voluntarily and to sign a written patient informed consent. Informed consent will be obtained from each Patient (or the subject's representative or relatives, depending on local regulations) according to Good Clinical Practice and regulatory and legal requirements of the participating country. Patients who are unable to sign but who are able to understand the meaning of participation in the study may give an oral witnessed informed consent. These patients have to make clear undoubtfully that they are wiling to participate voluntarily and must be able to understand an Explanation of the contents of the Information sheet
- Patient's life expectancy is at least 30 days (investigator's judgement)
Exclusion Criteria:
- Presence of only minor stroke symptoms as characterised by a NIH score of < 4 at the time of randomisation
- Severe obtundation as defined by a NIH Stroke Scale score of ≥ 2 using the Level of Consciousness category; including coma or severe stupor
Any patient with a concurrent, severe neurological disease
- Dementia, multi-infarct dementia
- Multiple sclerosis
- Previous stroke with residual deficit (i.e. pre-stroke modified Rankin Scale (mRS) must be ≤ 1). Tomographic or clinical evidence of brain stem infarct, any intracranial haemorrhage, primary or metastatic brain tumour, meningioma, or other space occupying lesion (e.g., subdural or epidural haematoma)
- Patient with history of seizure related or not to their stroke diagnosis, except seizure secondary to fever in the childhood
- Any patients with a concurrent mental deficit (e.g., AXIS-I psychiatric disorders as defined by the Diagnostic and Statistical Manual (DSM) IV criteria: schizophrenia, mood disorders (mania or major depression), psychotic/delusional disorders, a recent history (6 months) or current evidence of alcohol or recreational drug abuse
- Baseline blood glucose values below 2.75 mmol/l (hypoglycaemia) or above 22.0 mmol/l (hyperglycaemia)
- Sustained supine hypertension during the baseline period, and prior to randomisation, as defined as two readings 30 minutes apart with a systolic blood pressure ≥ 220 mmHg and/or a diastolic blood pressure ≥ 120 mmHg; and/or clinical diagnosis of malignant hypertensive crisis accompanied by other signs or symptoms (e.g. nausea, vomiting, obtundation, etc.) or complications (e.g. papilledema, retinal haemorrhage, hematuria, or congestive heart failure)
- Patients with known history of orthostatic hypotension, fainting spells or blackouts. Hypotension as defined by a systolic blood pressure ≤ 90 mmHg or a diastolic blood pressure ≤ 50 mmHg
- Patients currently on oral anticoagulants. A time window of at least two days should be observed when such a treatment has been administered and stopped before the beginning of the trial
Known history of a serious, advanced, unstable or terminal illness that in the opinion of the clinical investigator may interfere with the trial by confounding the results or pose an additional risk:
- cardiogenic shock, congestive heart failure (NYHA Class III-IV), acute myocardial infarction or history of a myocardial infarction within the past three months, unstable angina
- renal failure, severe hepatic disease, unstable gastrointestinal, pulmonary, metabolic, immunological, hormonal disorders
- cancer (except local skin cancers, e.g.: basal or squamous carcinoma)
- HIV+
- Females who are lactating or pregnant (as determined by a pregnancy test during screening) or of childbearing potential
- Current or recent (within 3 months) participation in another investigational drug protocol
- Patient cannot be followed for 30 days (according to the judgement of the investigator)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
BIII 890 CL
Placebo
Arm Description
escalating doses
Outcomes
Primary Outcome Measures
Number of patients with adverse events
Number of patients with clinically relevant findings in vital signs
Number of patients with clinically relevant findings in electrocardiogram (ECG)
Number of patients with clinically relevant findings in laboratory evaluation
Secondary Outcome Measures
Maximum concentration in plasma
Time to reach maximum concentration in plasma
Terminal elimination half-life
Terminal rate constant
Area under the plasma concentration-time curve
Mean residence time
Plasma clearance
Volume of distribution at steady state
Glutamate plasma concentrations
Change in modified Rankin Scale
Barthel Index
Change in NIH stroke scale
Full Information
NCT ID
NCT02251197
First Posted
September 25, 2014
Last Updated
September 25, 2014
Sponsor
Boehringer Ingelheim
1. Study Identification
Unique Protocol Identification Number
NCT02251197
Brief Title
Safety and Tolerability of BIII 890 in Patients With Acute Ischemic Stroke
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)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
July 2001 (undefined)
Primary Completion Date
October 2002 (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 study is to assess the safety, tolerability and pharmacokinetic characteristics of BIII 890 after intravenous infusion in acute ischemic stroke patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
97 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BIII 890 CL
Arm Type
Experimental
Arm Description
escalating doses
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
BIII 890 CL
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Number of patients with adverse events
Time Frame
up to 45 days
Title
Number of patients with clinically relevant findings in vital signs
Time Frame
up to 30 days
Title
Number of patients with clinically relevant findings in electrocardiogram (ECG)
Time Frame
up to 45 days
Title
Number of patients with clinically relevant findings in laboratory evaluation
Time Frame
up to 45 days
Secondary Outcome Measure Information:
Title
Maximum concentration in plasma
Time Frame
up to 120 hours after drug administration
Title
Time to reach maximum concentration in plasma
Time Frame
up to 120 hours after drug administration
Title
Terminal elimination half-life
Time Frame
up to 120 hours after drug administration
Title
Terminal rate constant
Time Frame
up to 120 hours after drug administration
Title
Area under the plasma concentration-time curve
Time Frame
up to 120 hours after drug administration
Title
Mean residence time
Time Frame
up to 120 hours after drug administration
Title
Plasma clearance
Time Frame
up to 120 hours after drug administration
Title
Volume of distribution at steady state
Time Frame
up to 120 hours after drug administration
Title
Glutamate plasma concentrations
Time Frame
up to 72 hours after start of infusion
Title
Change in modified Rankin Scale
Time Frame
Baseline, day 30
Title
Barthel Index
Time Frame
Day 30
Title
Change in NIH stroke scale
Time Frame
Baseline, day 1, 3, 7 and 30
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female patients aged 18 years or above
Patients with an acute onset of a focal neurological deficit secondary to a lesion presumed to be ischemic in etiology involving the carotid and/or vertebrobasilar artery territories
Onset of symptoms within 24 hours prior to initiation of administration of study drug. If the patient has awakened from sleep with the deficit, the time of onset will be considered as the last time he/she was normal
Stroke symptoms are to be present for at least 1 hour and are still present at randomisation. Symptoms must be distinguishable from an episode of generalised ischemia (i.e. syncope), seizure, migraine or hypoglycaemic disorder
Patient is willing to participate voluntarily and to sign a written patient informed consent. Informed consent will be obtained from each Patient (or the subject's representative or relatives, depending on local regulations) according to Good Clinical Practice and regulatory and legal requirements of the participating country. Patients who are unable to sign but who are able to understand the meaning of participation in the study may give an oral witnessed informed consent. These patients have to make clear undoubtfully that they are wiling to participate voluntarily and must be able to understand an Explanation of the contents of the Information sheet
Patient's life expectancy is at least 30 days (investigator's judgement)
Exclusion Criteria:
Presence of only minor stroke symptoms as characterised by a NIH score of < 4 at the time of randomisation
Severe obtundation as defined by a NIH Stroke Scale score of ≥ 2 using the Level of Consciousness category; including coma or severe stupor
Any patient with a concurrent, severe neurological disease
Dementia, multi-infarct dementia
Multiple sclerosis
Previous stroke with residual deficit (i.e. pre-stroke modified Rankin Scale (mRS) must be ≤ 1). Tomographic or clinical evidence of brain stem infarct, any intracranial haemorrhage, primary or metastatic brain tumour, meningioma, or other space occupying lesion (e.g., subdural or epidural haematoma)
Patient with history of seizure related or not to their stroke diagnosis, except seizure secondary to fever in the childhood
Any patients with a concurrent mental deficit (e.g., AXIS-I psychiatric disorders as defined by the Diagnostic and Statistical Manual (DSM) IV criteria: schizophrenia, mood disorders (mania or major depression), psychotic/delusional disorders, a recent history (6 months) or current evidence of alcohol or recreational drug abuse
Baseline blood glucose values below 2.75 mmol/l (hypoglycaemia) or above 22.0 mmol/l (hyperglycaemia)
Sustained supine hypertension during the baseline period, and prior to randomisation, as defined as two readings 30 minutes apart with a systolic blood pressure ≥ 220 mmHg and/or a diastolic blood pressure ≥ 120 mmHg; and/or clinical diagnosis of malignant hypertensive crisis accompanied by other signs or symptoms (e.g. nausea, vomiting, obtundation, etc.) or complications (e.g. papilledema, retinal haemorrhage, hematuria, or congestive heart failure)
Patients with known history of orthostatic hypotension, fainting spells or blackouts. Hypotension as defined by a systolic blood pressure ≤ 90 mmHg or a diastolic blood pressure ≤ 50 mmHg
Patients currently on oral anticoagulants. A time window of at least two days should be observed when such a treatment has been administered and stopped before the beginning of the trial
Known history of a serious, advanced, unstable or terminal illness that in the opinion of the clinical investigator may interfere with the trial by confounding the results or pose an additional risk:
cardiogenic shock, congestive heart failure (NYHA Class III-IV), acute myocardial infarction or history of a myocardial infarction within the past three months, unstable angina
renal failure, severe hepatic disease, unstable gastrointestinal, pulmonary, metabolic, immunological, hormonal disorders
cancer (except local skin cancers, e.g.: basal or squamous carcinoma)
HIV+
Females who are lactating or pregnant (as determined by a pregnancy test during screening) or of childbearing potential
Current or recent (within 3 months) participation in another investigational drug protocol
Patient cannot be followed for 30 days (according to the judgement of the investigator)
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com
Description
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Safety and Tolerability of BIII 890 in Patients With Acute Ischemic Stroke
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