Study to Assess the Safety, Pharmacokinetics/Dynamics of DS-1040b in Subjects With Acute Submassive Pulmonary Embolism

NCT ID: NCT02923115

Last Updated: 2023-04-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 134 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-23
• Study Completion Date: 2019-08-05

Brief Summary

This is a Phase 1b, double-blind (participants and Investigators), placebo-controlled, randomized, single-ascending dose, multi-center study to assess the safety, efficacy, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DS-1040b in participants with acute submassive pulmonary embolism.

Conditions

Pulmonary Embolism; Thrombotic Disease

Study Design

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

Study Groups

DS-1040b

Participants who are randomized to receive DS-1040b as a single, continuous intravenous infusion (initial loading dose 3-6 mg). All participants will also receive standard of care anticoagulation enoxaparin therapy during the study drug infusion.

Group Type: EXPERIMENTAL

DS-1040b

Intervention Type: DRUG

Single, continuous intravenous infusion over 12 to 24 hours (depending on cohort)

Enoxaparin

Intervention Type: DRUG

Subcutaneous injection 1 mg/kg twice daily

Placebo

Participants who are randomized to receive placebo as a single, continuous intravenous infusion. All participants will also receive standard of care anticoagulation enoxaparin therapy during the study drug infusion.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Single, continuous intravenous infusion of 0.9% sodium chloride over 12 to 24 hours

Enoxaparin

Intervention Type: DRUG

Subcutaneous injection 1 mg/kg twice daily

Interventions

DS-1040b

Single, continuous intravenous infusion over 12 to 24 hours (depending on cohort)

Intervention Type: DRUG

Placebo

Single, continuous intravenous infusion of 0.9% sodium chloride over 12 to 24 hours

Intervention Type: DRUG

Enoxaparin

Subcutaneous injection 1 mg/kg twice daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female subjects, age 18 to 75 years admitted to hospital with a clinical diagnosis of acute pulmonary embolism (PE) categorized as low risk or intermediate-risk or submassive PE and for whom catheter-based therapy is not planned;
• Subjects must have a computed tomography angiography (CTA) scan confirming the PE diagnosis and with at least one measurable index lesion in a segmental or larger pulmonary artery prior to randomization;
• Subjects should be in otherwise satisfactory health in the opinion of the Investigator;
• Subjects must be able to provide written informed consent.

Exclusion Criteria

• Subjects with acute PE categorized as high-risk or massive, or who are hemodynamically unstable, evidenced by a heart rate > 120 /min and a systolic blood pressure (SBP) of < 90 mmHg for more than 15 consecutive minutes or a drop in SBP of > 40 mmHg since presentation;
• Subjects for whom use of a thrombolytic, either systemic or via catheter, is planned;
• Subjects with PE lesions only in the sub-segmental or smaller arteries;
• Subjects receiving any vitamin K antagonists (VKAs) prior to randomization or receiving more than 36 hours treatment with low molecular weight (LMW) Heparin in therapeutic doses prior to randomization;
• Subjects who had a prior intracranial hemorrhage, known arteriovenous malformation or aneurysm, head trauma, or evidence of active bleeding;
• Subjects who within 48 hours of randomization have used an anti-Factor IIa agent such as dabigatran or an anti-FXa agent such as rivaroxaban, apixaban, or edoxaban;
• Subjects who within 21 days prior to randomization have had gastrointestinal or genitourinary bleeding;
• Subjects who within 14 days prior to randomization have had major surgery or a lumbar puncture (or epidural steroid injection);
• Subjects with diagnosed active liver disease or with elevation of liver enzymes/bilirubin.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Study Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

Pulmonary Associates of Mobile

Mobile, Alabama, United States

Cedars-Sinai Medical Center

Beverly Hills, California, United States

University of California, San Diego (UCSD) Medical Center

San Diego, California, United States

Intercoastal Medical Group

Sarasota, Florida, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

University of Kentucky Medical Center

Lexington, Kentucky, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Mercury Street Medical

Butte, Montana, United States

NYU Radiology Associate

New York, New York, United States

Jacobi Medical Center

The Bronx, New York, United States

Duke University Medical Center (DUMC)

Durham, North Carolina, United States

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Capital Area Research

Camp Hill, Pennsylvania, United States

Temple University Hospital

Philadelphia, Pennsylvania, United States

Medical University Graz

Graz, , Austria

Medical University Innsbruck

Innsbruck, , Austria

Medical University of Vienna

Vienna, , Austria

Universite Libre de Bruxelles (ULB) - Hopital Erasme

Brussels, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

University Hospital Leuven

Leuven, , Belgium

CHU de Brest - Hopital de la Cavale Blanche

Brest, , France

CHU Gabriel Montpied Clermont-Ferrand

Clermont-Ferrand, , France

CHU de Grenoble

La Tronche, , France

Hopital Europeen Georges Pompidou

Paris, , France

CHU St Etienne - Hopital Nord

Saint-Etienne, , France

Hopital Civil de Strasbourg

Strasbourg, , France

Staedtisches Klinikum Dresden-Friedrichstadt

Dresden, , Germany

Universitaetsklinikum Dresden

Dresden, , Germany

Universitaetsmedizin Greifswald

Greifswald, , Germany

Universitatsklinikum Magdeburg

Magdeburg, , Germany

Klinikum rechts der Isar, Technische Universität München

München, , Germany

AOU Ospedali Riuniti di Ancona

Ancona, , Italy

Universit degli Studi di Perugia - Azienda Ospedaliera di Perugia

Perugia, , Italy

Humanitas Research Hospital

Rozzano, , Italy

Ospedale di Circolo

Varese, , Italy

Noordwest Ziekenhuisgroep

Alkmaar, , Netherlands

Academisch Medisch Centrum

Amsterdam, , Netherlands

Albert Schweitzer Hospital

Dordrecht, , Netherlands

Leiden University Medical Center - Leids Universitair Medisch Centrum (LUMC)

Leiden, , Netherlands

HagaZiekenhuis

The Hague, , Netherlands

UMC Utrecht

Utrecht, , Netherlands

Hospital Universitario

Girona, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Hospital Clinico San Carlos

Madrid, , Spain

Hospital Virgen del Rocío

Seville, , Spain

Countries

United States; Austria; Belgium; France; Germany; Italy; Netherlands; Spain

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2015-005211-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DS1040-B-U107

Identifier Type: -

Identifier Source: org_study_id