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Trial record 1 of 2 for:    ASSENT | stroke
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Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of DS-1040b in Subjects With Acute Ischemic Stroke (ASSENT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02586233
Recruitment Status : Completed
First Posted : October 26, 2015
Last Update Posted : September 10, 2019
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Tracking Information
First Submitted Date  ICMJE October 21, 2015
First Posted Date  ICMJE October 26, 2015
Last Update Posted Date September 10, 2019
Actual Study Start Date  ICMJE September 2015
Actual Primary Completion Date May 16, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 15, 2018)
Number of participants with treatment emergent adverse events [ Time Frame: from first dose to 90 days post-dose ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 23, 2015)
Number and severity of adverse events [ Time Frame: 18 months ]
To count the number and severity of treatment emergent adverse events (TEAEs) within 3 to 8 hours after stroke symptoms onset
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 15, 2018)
  • Area under the plasma concentration-time curve from time zero to 24 hours (AUC24) for DS-1040b [ Time Frame: within 24 hours post-dose ]
  • Maximum concentration (Cmax) of DS-1040b in plasma [ Time Frame: within 24 hours post-dose ]
  • Time to Cmax (Tmax) for DS-1040b in plasma [ Time Frame: within 24 hours post-dose ]
  • Urinary excretion within 24 hours (Ae0-24) of DS-1040b [ Time Frame: within 24 hours post-dose ]
  • Thrombin-activatable fibrinolysis inhibitor (TAFI) antigen in plasma [ Time Frame: 24 hours post-dose ]
  • D-dimer level in plasma [ Time Frame: 24 hours post-dose ]
  • Total activated thrombin-activatable fibrinolysis inhibitor in plasma [ Time Frame: 24 hours post-dose ]
  • Number of participants with recanalization of occlusion at 24 hours [ Time Frame: 24 hours post-dose ]
  • Change from baseline in National Institute of Health Stroke Scale (NIHSS) score from predose to 30 days post-dose [ Time Frame: Baseline, Day 30 ]
    The National Institutes of Health Stroke Scale, or NIH Stroke Scale (NIHSS) is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4.
  • Change from baseline in modified Rankin Scale (mRS) score at Day 90 [ Time Frame: Baseline, Day 90 ]
    The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The mRS is a scale of 0-6, where 0=perfect health and 6=death.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2015)
  • Pharmacokinetic parameter, area under concentration curve (AUC) of DS-1040b in plasma [ Time Frame: 24 hours after dose ]
    Pharmacokinetic parameter AUC of DS-1040b in plasma
  • Pharmacokinetic parameter, tmax of DS-1040b in plasma [ Time Frame: 24 hours after dose ]
    Pharmacokinetic parameter tmax of DS-1040b in plasma
  • Pharmacokinetic parameter, maximum concentration Cmax of DS-1040b in plasma [ Time Frame: 24 hours after dose ]
    Pharmacokinetic parameter Cmax of DS-1040b in plasma
  • Pharmacokinetic parameter, amount of drug excreted in urine of DS-1040b in plasma [ Time Frame: 24 hours after dose ]
    Pharmacokinetic parameter amount of drug excreted in urine (Ae0-24) of DS-1040b in plasma
  • analysis for thrombin-activatable fibrinolysis inhibitor (TAFIa) antigen in plasma [ Time Frame: 24 hours after dose ]
    Pharmacodynamic analysis for thrombin-activatable fibrinolysis inhibitor (TAFIa) antigen in plasma
  • analysis for clot lysis in plasma [ Time Frame: 24 hours after dose ]
    Pharmacodynamic analysis for clot lysis (an exploratory biomarker) in plasma
  • analysis for D-dimer in plasma [ Time Frame: 24 hours after dose ]
    Pharmacodynamic analysis for D-dimer in plasma
  • analysis for total thrombin-activatable fibrinolysis inhibitor in plasma [ Time Frame: 24 hours after dose ]
    Pharmacodynamic analysis for total thrombin-activatable fibrinolysis inhibitor (total TAFIa) activity in plasma
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of DS-1040b in Subjects With Acute Ischemic Stroke
Official Title  ICMJE A Phase 1b/2, Multi-Center, Double-Blind (Principal Investigators and Study Subjects Blinded, Sponsor Unblinded), Placebo-Controlled, Randomized, Single-Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of DS-1040b in Subjects With Acute Ischemic Stroke
Brief Summary This is a Phase 1b/2, double-blind (Principal Investigators and study subjects blinded, Sponsor unblinded), placebo-controlled, randomized, single-ascending dose, multi-center study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DS-1040b in subjects with Acute Ischemic Stroke (AIS).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Ischemic Stroke
  • Thrombotic Disease
Intervention  ICMJE
  • Drug: DS-1040b
    DS-1040b for IV administration
    Other Name: Experimental product
  • Drug: Placebo
    Matching placebo for IV administration
    Other Name: Placebo comparator
Study Arms  ICMJE
  • Experimental: DS-1040b
    Intravenous (IV) infusion of DS-1040b ranging from 0.6 mg to 9.6 mg of DS-1040b
    Intervention: Drug: DS-1040b
  • Placebo Comparator: Placebo
    IV infusion of placebo
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 6, 2019)
106
Original Estimated Enrollment  ICMJE
 (submitted: October 23, 2015)
96
Actual Study Completion Date  ICMJE August 13, 2019
Actual Primary Completion Date May 16, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Has a clinical diagnosis of acute ischemic stroke (including lacunar stroke/infarct) supported by computed topography or magnetic resonance imaging to rule out alternative cause for presenting symptoms
  • Has onset of stroke symptoms within 4.5 to 12 hours before initiation of study drug administration - for subjects with a stroke upon waking, time of symptom onset is the last time the subject was known to be well
  • Has a NIHSS score of ≥ 2 (for Cohorts 1-5) and ≥ 5 (for Cohort 6)
  • Has Low dose heparin or low molecular weight heparin at a preventive dose are allowed from 24 hours after treatment start completion and after confirmation of no intracranial bleeding on the 24-hours repeat brain imaging.
  • Is a Cohort 6 participant who is treated or anticipated to be treated with intra-arterial therapy (IAT) for ischemic stroke at the time of randomization (for enrollment in the IAT subgroup)
  • Has given written informed consent to participate in the study prior to participating in any study-related procedures - depending on country-specific practice, written informed consent may be acceptable from legally authorized representative
  • Has given a separate written informed consent for collecting a blood sample for genotyping

Exclusion Criteria:

  • Is a Cohort 1-5 participant who has been treated or is going to be treated with tissue plasminogen activator (tPA) and/or endovascular thrombectomy during current stroke
  • Is a Cohort 6 participant treated or anticipated to be treated with tPA during current stroke
  • Has evidence of intracranial hemorrhage on non-contrast computed tomography (CT/CAT) scan or magnetic resonance imaging (MRI)
  • Has symptoms of subarachnoid hemorrhage, even with normal imaging
  • Has an Alberta Stroke Program Early CT Score (ASPECTS) <6
  • Has prior non-traumatic intracranial hemorrhage (excluding microhemorrhages observed in imaging)
  • Has known arteriovenous malformation or aneurysm
  • Has evidence of active bleeding
  • Has platelet count less than 100,000
  • Has International Normalized Ratio greater than 1.7
  • Has used unfractionated heparin within 24 hours prior to treatment and has an elevated partial thromboplastin time
  • Has used a non-vitamin K antagonist oral anticoagulant such as dabigatran, rivaroxaban, apixaban, or other factor Xa inhibitors within 24 hours before treatment
  • Has used fondaparinux or low molecular weight heparin at an anticoagulation dose within 24 hours prior to treatment
  • Has anticipated use of an anticoagulation dose of heparin, or fondaparinux or low molecular weight heparin, or nonvitamin K antagonist oral anticoagulant such as dabigatran, rivaroxaban, apixaban, or other factor Xa inhibitors within 48 hours after completion of study drug treatment (low dose heparin or low molecular weight heparin at a preventive dose are allowed from 24 hours after treatment completion and after confirmation of no intracranial bleeding on the 24 hours repeat brain imaging. In Cohort 6, heparin treatment associated with IAT is allowed.)
  • Has blood pressure > 185/110 mmHg, or requires aggressive medication to maintain blood pressure below this limit (routine medical treatment including IV drug treatment is allowed to lower the blood pressure below this limit)
  • Has had intracranial surgery, clinically significant head trauma (in the opinion of Principal Investigator), Alteplase treatment, or a previous stroke within 1 month
  • Has had major surgery within 14 days
  • Has had gastrointestinal or genitourinary bleeding in the last 21 days
  • Has had a lumbar puncture (or epidural steroid injection) within 14 days
  • Has had a preexisting disability classified by mRS > 2
  • Has an estimated glomerular filtration rate < 60 mL/min/1.73 m^2
  • Has baseline hemoglobin < 10.5 g/dL
  • Has a positive pregnancy test
  • Is currently participating in another investigational study or has participated in an investigational drug study within 30 days or 5 half-lives of that investigational drug prior to administration of the study drug
  • Is an employee or an immediate family member of an employee of the Sponsor, the Contract Research Organization (CRO), or the Site
  • Has any other condition the investigator determines would preclude participation in the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Czechia,   France,   Germany,   Italy,   Korea, Republic of,   Slovakia,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries Canada
 
Administrative Information
NCT Number  ICMJE NCT02586233
Other Study ID Numbers  ICMJE DS1040-A-U103
2015-001824-43 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/
Responsible Party Daiichi Sankyo, Inc.
Study Sponsor  ICMJE Daiichi Sankyo, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
PRS Account Daiichi Sankyo, Inc.
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP