Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of DS-1040b in Subjects With Acute Ischemic Stroke (ASSENT)

Daiichi Sankyo

Status and phase

Completed

Phase 2

Phase 1

Conditions

Thrombotic Disease

Acute Ischemic Stroke

Treatments

Drug: DS-1040b

Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT02586233

2015-001824-43 (EudraCT Number)

DS1040-A-U103

Details and patient eligibility

About

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).

Enrollment

106 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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