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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
Results First Posted : September 9, 2020
Last Update Posted : September 9, 2020
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Brief Summary:
This is a Phase 1b/2, double-blind (study participants and Investigators), placebo-controlled, randomized, single-ascending dose, multi-center study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DS-1040b in participants with Acute Ischemic Stroke (AIS).

Condition or disease Intervention/treatment Phase
Acute Ischemic Stroke Thrombotic Disease Drug: DS-1040b Drug: Placebo Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 106 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 2015
Actual Primary Completion Date : August 13, 2019
Actual Study Completion Date : August 13, 2019

Arm Intervention/treatment
Experimental: DS-1040b
Participants who will be randomized to receive intravenous (IV) infusion of DS-1040b ranging from 0.6 mg to 9.6 mg.
Drug: DS-1040b
DS-1040b for IV infusion (0.6 mg to 9.6 mg) over 6-hour period
Other Name: Experimental product

Placebo Comparator: Placebo
Participants who will be randomized to receive intravenous (IV) infusion of placebo.
Drug: Placebo
0.9% sodium chloride (placebo comparator) for IV infusion over 6-hour period




Primary Outcome Measures :
  1. Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke [ Time Frame: Baseline up to 90 days post last dose, up to 3 years 11 months ]
    Treatment-emergent adverse event (TEAE) is defined as an adverse event that emerges during the treatment period (from first dose date until 30 days after the last dosing date), having been absent at predose; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pre-dose state, when the adverse event is continuous.


Secondary Outcome Measures :
  1. Summary of Pharmacokinetic (PK) Parameter Maximum (Peak) Observed Plasma Concentration (Cmax) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke [ Time Frame: Predose, 0.5, 3, 6, 9, 12, 24, 48, 72, and 96 hours postdose ]
    The PK parameter of Maximum (Peak) Observed Plasma Concentration (Cmax) of DS-1040b was calculated from the plasma concentrations of DS-1040b using non-compartmental analysis

  2. Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve From Zero to Last Quantifiable Concentration Sampling Point (AUClast) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke [ Time Frame: Predose, 0.5, 3, 6, 9, 12, 24, 48, 72, and 96 hours postdose ]
    The PK parameter of Area Under the Concentration Versus Time Curve from Zero to Last Quantifiable Concentration Sampling Point of DS-1040b was calculated from the plasma concentrations of DS-1040b using non-compartmental analysis

  3. Summary of Pharmacokinetic Parameter Terminal Half-life (t1/2) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke [ Time Frame: Pre-dose, 0.5, 3, 6, 9, 12, 24, 48, 72, and 96 hours post-dose ]
    The PK parameter of Terminal Half-life of DS-1040b was calculated from the plasma concentrations of DS-1040b using non-compartmental analysis in patients with available sample for the analysis.

  4. Summary of Activated Form of Thrombin-activatable Fibrinolysis Inhibitor (TAFIa) Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke [ Time Frame: Baseline and 6 hours postdose ]
    The enzymatic activity of thrombin-activatable fibrinolysis inhibitor was assessed using the Stago Coagulation Analyzer.

  5. Summary of Changes From Baseline at Day 30 in National Institute of Health Stroke Scale (NIHSS) Score Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke [ Time Frame: 30 days post dose ]
    The National Institute of Health Stroke Scale (NIHSS) quantifies stroke severity based on weighted evaluation findings. The score for each ability is a number between 0 and 4, with 0 being normal functioning and 4 being completely impaired. The patient's NIHSS score is calculated by adding the number for each element of the scale; 42 is the highest score possible. In the NIHSS, the higher the score indicates more impairment (worse outcome) in a stroke patient.

  6. Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 to 2 Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke [ Time Frame: Day 5 (baseline) and Day 90 post dose ]
    The modified Rankin scale (mRS) is a commonly used disability scale derived from the Rankin scale that is used to measure the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The level of disability following a stroke is assessed via a scale from 0 to 6, where 0 is no symptoms at all and 6 indicates death. Higher scores indicate worse outcome. The percentage of participants with an mRS score of 0 to 2 at Day 5 (baseline) and Day 90 is being reported.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 modified Rankin Scale (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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02586233


Locations
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Sponsors and Collaborators
Daiichi Sankyo, Inc.
Investigators
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Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
  Study Documents (Full-Text)

Documents provided by Daiichi Sankyo, Inc.:
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Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT02586233    
Other Study ID Numbers: DS1040-A-U103
2015-001824-43 ( EudraCT Number )
First Posted: October 26, 2015    Key Record Dates
Results First Posted: September 9, 2020
Last Update Posted: September 9, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
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/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Daiichi Sankyo, Inc.:
Acute Ischemic Stroke
Thrombotic disease
DS-1040b
Additional relevant MeSH terms:
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Stroke
Cerebral Infarction
Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Infarction
Brain Ischemia