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

NCT ID: NCT02586233

Last Updated: 2020-09-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2019-08-13

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).

Conditions

Acute Ischemic Stroke; Thrombotic Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

DS-1040b

Participants who will be randomized to receive intravenous (IV) infusion of DS-1040b ranging from 0.6 mg to 9.6 mg.

Group Type: EXPERIMENTAL

DS-1040b

Intervention Type: DRUG

DS-1040b for IV infusion (0.6 mg to 9.6 mg) over 6-hour period

Placebo

Participants who will be randomized to receive intravenous (IV) infusion of placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

0.9% sodium chloride (placebo comparator) for IV infusion over 6-hour period

Interventions

DS-1040b

DS-1040b for IV infusion (0.6 mg to 9.6 mg) over 6-hour period

Intervention Type: DRUG

Placebo

0.9% sodium chloride (placebo comparator) for IV infusion over 6-hour period

Intervention Type: DRUG

Other Intervention Names

Experimental product

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

University of South Alabama USA Health System

Mobile, Alabama, United States

UCLA Medical Center Stroke Network

Los Angeles, California, United States

UC Health Memorial Hospital

Colorado Springs, Colorado, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Kentucky Chandler Medical Center

Lexington, Kentucky, United States

University of Louisville

Louisville, Kentucky, United States

Henry Ford Health System

Detroit, Michigan, United States

JFK Neuroscience Institute

Edison, New Jersey, United States

Icahn School Medicine at Mount Sinai

New York, New York, United States

Duke University Health System

Durham, North Carolina, United States

OSU - Wexner Medical Center

Columbus, Ohio, United States

Oregon Health Sciences University Hospital

Portland, Oregon, United States

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Palmetto Health, USC School of Medicine

Columbia, South Carolina, United States

Chattanooga Center for Neurologic Research

Chattanooga, Tennessee, United States

Houston Methodist

Houston, Texas, United States

Royal North Shore Hospital

Sydney, New South Wales, Australia

Royal Adelaide Hospital Neurology Dept.

Adelaide, South Australia, Australia

Monash Health

Clayton, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

St. Annes University Hospital

Brno, , Czechia

Vitkovicka nemocnice a.s. Zaluzanskeho

Ostrava Vitkovice, , Czechia

CHRU Besançon - Hôpital Jean Minjoz

Besançon, , France

Hôpital Pellegrin - CHU Bordeaux

Bordeaux, , France

CHRU Lille - Hôpital Roger Salengro

Lille, , France

Klinikum Altenburger Land

Altenburg, , Germany

Universittsklinikum Essen AR Klinik fr Neurologie

Essen, , Germany

Klinikum der Johann Wolfgang Goethe-Universitat

Frankfurt am Main, , Germany

Ospedale di Citta di Castello

Città di Castello, , Italy

Ospedale di Branca Largo Unita d'Italia

Gubbio, , Italy

Ospedale Guglielmo da Saliceto Via Taverna

Piacenza, , Italy

Ospedaliero di Albenga - Pietra Ligure Dept Neurology

Pietra Ligure, , Italy

Azienda Ospedaliero Universitaria

Pisa, , Italy

Ospedale Borgo Trento

Verona, , Italy

Svet zdravia a.s.,Vseobecna nemocnica Rimavska Sobota

Rimavská Sobota, , Slovakia

NsP Spisska Nova Ves

Spišská Nová Ves, , Slovakia

Pusan National University Hospital

Busan, , South Korea

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Samsung Medical Center

Seoul, , South Korea

Hospital de la santa creu i sant pau C

Barcelona, , Spain

Vall d'Hebron Hospital

Barcelona, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Clínico Universitario de Santiago de Compostela

Santiago de Compostela, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Hospital Virgen del Rocio

Seville, , Spain

Hospital Clinico Universitario de Valladolid

Valladolid, , Spain

Hospital Clinico Universitario Lozano Blesa de Zaragoza

Zaragoza, , Spain

Chang Gung Memorial Hospital-Linkou Branch

Taoyuan District, Hsien, Taiwan

China Medical University Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

University College Hospitals NHS Foundation Trust

London, England, United Kingdom

Queen Elizabeth University Hospital

Glasgow, Scotland, United Kingdom

Salford Royal Hospital

Salford, , United Kingdom

Royal Stoke University Hospital

Stoke-on-Trent, , United Kingdom

Countries

United States; Australia; Czechia; France; Germany; Italy; Slovakia; South Korea; Spain; Taiwan; United Kingdom

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2015-001824-43

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DS1040-A-U103

Identifier Type: -

Identifier Source: org_study_id