Back to resultsStudy to Assess the Safety, Pharmacokinetics/Dynamics of DS-1040b in Subjects With Acute Submassive Pulmonary Embolism
Primary Purpose
Pulmonary Embolism, Thrombotic Disease
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
DS-1040b
Placebo
Enoxaparin
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Embolism focused on measuring Venous thromboembolism (VTE), Pulmonary embolism (PE), Acute Submassive Pulmonary Embolism
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.
Sites / Locations
- Pulmonary Associates of Mobile
- Cedars-Sinai Medical Center
- University of California, San Diego (UCSD) Medical Center
- Intercoastal Medical Group
- Northwestern Memorial Hospital
- University of Kentucky Medical Center
- Massachusetts General Hospital
- Mayo Clinic - Rochester
- Mercury Street Medical
- Jacobi Medical Center
- NYU Radiology Associate
- Duke University Medical Center (DUMC)
- The Cleveland Clinic Foundation
- Capital Area Research
- Temple University Hospital
- Medical University Graz
- Medical University Innsbruck
- Medical University of Vienna
- Universite Libre de Bruxelles (ULB) - Hopital Erasme
- Cliniques Universitaires Saint-Luc
- University Hospital Leuven
- CHU de Brest - Hopital de la Cavale Blanche
- CHU Gabriel Montpied Clermont-Ferrand
- CHU de Grenoble
- Hopital Europeen Georges Pompidou
- CHU St Etienne - Hopital Nord
- Hopital Civil de Strasbourg
- Staedtisches Klinikum Dresden-Friedrichstadt
- Universitaetsklinikum Dresden
- Universitaetsmedizin Greifswald
- Universitatsklinikum Magdeburg
- Klinikum rechts der Isar, Technische Universität München
- AOU Ospedali Riuniti di Ancona
- Universit degli Studi di Perugia - Azienda Ospedaliera di Perugia
- Humanitas Research Hospital
- Ospedale di Circolo
- Noordwest Ziekenhuisgroep
- Academisch Medisch Centrum
- Albert Schweitzer Hospital
- Leiden University Medical Center - Leids Universitair Medisch Centrum (LUMC)
- HagaZiekenhuis
- UMC Utrecht
- Hospital Universitario
- Hospital Universitario Ramon y Cajal
- Hospital Clinico San Carlos
- Hospital Virgen del Rocío
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
DS-1040b
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Number of Participants Experiencing Adjudicated Clinically Relevant Bleeding Events Following Intravenous Infusion of DS-1040b or Placebo in Addition to Standard of Care Anti-coagulation Therapy in Participants With Acute Submassive Pulmonary Embolism
Clinically relevant bleeding was defined as major or clinically relevant non-major (CRNM) bleeding adjudicated by the Clinical Events Committee (CEC) based on International Society of Thrombosis and Haemostasis (ISTH) definitions and the CEC charter.
Secondary Outcome Measures
Mean Percent Change From Baseline in Total Thrombus Volume at 12-72 Hours Post Start of Infusion of DS-1040b Compared to Placebo When Added to Standard of Care Anticoagulation Therapy in Participants With Acute Submassive Pulmonary Embolism
The change from baseline in total thrombus volume was assessed by computed tomography angiography in segmental or larger pulmonary arteries following intravenous infusion of DS-1040b or placebo in addition to standard of care anti-coagulation therapy.
Participants Achieving Reductions in Total Thrombus Volume at 12-72 Hours Post Infusion of DS-1040b Compared to Placebo When Added to Standard of Care Anticoagulation Therapy in Participants With Acute Submassive Pulmonary Embolism
Change in total pulmonary thrombus burden (total thrombus volume) was assessed by computed tomography pulmonary angiography (CTPA). All CTPA scans were evaluated by a central imaging laboratory in a blinded manner by radiologists.
Pharmacokinetic (PK) Parameter Maximum Concentration (CMax) Following Intravenous Infusion of DS-1040b in Addition to Standard of Care Anti-coagulation Therapy in Participants With Acute Submassive Pulmonary Embolism
Plasma concentrations at each time point and PK parameter Cmax of DS 1040b was calculated using non-compartmental analysis.
Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve (0 to Last) Following Intravenous Infusion of DS-1040b In Addition to Standard of Care Anti-coagulation Therapy in Participants With Acute Submassive Pulmonary Embolism
Plasma concentrations at each time point and PK parameter of Area Under the Concentration Versus Time Curve (0 to last) of DS-1040b was calculated using non-compartmental analysis.
Pharmacokinetic Parameter Terminal Half-life Following Intravenous Infusion of DS-1040b Combined With Standard of Care Anti-coagulation Therapy in Participants With Acute Submassive Pulmonary Embolism
Plasma concentrations at each time point and PK parameter Terminal Half-life of DS-1040b was calculated using non-compartmental analysis.
Full Information
NCT ID
NCT02923115
First Posted
September 30, 2016
Last Updated
April 18, 2023
Sponsor
Daiichi Sankyo, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02923115
Brief Title
Study to Assess the Safety, Pharmacokinetics/Dynamics of DS-1040b in Subjects With Acute Submassive Pulmonary Embolism
Official Title
A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Single Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of DS-1040b When Added to Standard of Care Anticoagulation Therapy in Subjects With Acute Submassive Pulmonary Embolism
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
June 23, 2016 (Actual)
Primary Completion Date
August 5, 2019 (Actual)
Study Completion Date
August 5, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Daiichi Sankyo, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Embolism, Thrombotic Disease
Keywords
Venous thromboembolism (VTE), Pulmonary embolism (PE), Acute Submassive Pulmonary Embolism
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
134 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DS-1040b
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
DS-1040b
Intervention Description
Single, continuous intravenous infusion over 12 to 24 hours (depending on cohort)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Single, continuous intravenous infusion of 0.9% sodium chloride over 12 to 24 hours
Intervention Type
Drug
Intervention Name(s)
Enoxaparin
Intervention Description
Subcutaneous injection 1 mg/kg twice daily
Primary Outcome Measure Information:
Title
Number of Participants Experiencing Adjudicated Clinically Relevant Bleeding Events Following Intravenous Infusion of DS-1040b or Placebo in Addition to Standard of Care Anti-coagulation Therapy in Participants With Acute Submassive Pulmonary Embolism
Description
Clinically relevant bleeding was defined as major or clinically relevant non-major (CRNM) bleeding adjudicated by the Clinical Events Committee (CEC) based on International Society of Thrombosis and Haemostasis (ISTH) definitions and the CEC charter.
Time Frame
Baseline up to Day 30 post infusion, up to approximately 3 years 2 months
Secondary Outcome Measure Information:
Title
Mean Percent Change From Baseline in Total Thrombus Volume at 12-72 Hours Post Start of Infusion of DS-1040b Compared to Placebo When Added to Standard of Care Anticoagulation Therapy in Participants With Acute Submassive Pulmonary Embolism
Description
The change from baseline in total thrombus volume was assessed by computed tomography angiography in segmental or larger pulmonary arteries following intravenous infusion of DS-1040b or placebo in addition to standard of care anti-coagulation therapy.
Time Frame
Baseline to 12-72 hours post start of infusion, up to approximately 3 years 2 months
Title
Participants Achieving Reductions in Total Thrombus Volume at 12-72 Hours Post Infusion of DS-1040b Compared to Placebo When Added to Standard of Care Anticoagulation Therapy in Participants With Acute Submassive Pulmonary Embolism
Description
Change in total pulmonary thrombus burden (total thrombus volume) was assessed by computed tomography pulmonary angiography (CTPA). All CTPA scans were evaluated by a central imaging laboratory in a blinded manner by radiologists.
Time Frame
Baseline to 12-72 hours post start of infusion, up to approximately 3 years 2 months
Title
Pharmacokinetic (PK) Parameter Maximum Concentration (CMax) Following Intravenous Infusion of DS-1040b in Addition to Standard of Care Anti-coagulation Therapy in Participants With Acute Submassive Pulmonary Embolism
Description
Plasma concentrations at each time point and PK parameter Cmax of DS 1040b was calculated using non-compartmental analysis.
Time Frame
Cohort 1: 0 up to 72 h post infusion; Cohorts 2 and 3: 0 up to 96 h post infusion; Cohort 4 and 5: 0 up to 120 h post infusion
Title
Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve (0 to Last) Following Intravenous Infusion of DS-1040b In Addition to Standard of Care Anti-coagulation Therapy in Participants With Acute Submassive Pulmonary Embolism
Description
Plasma concentrations at each time point and PK parameter of Area Under the Concentration Versus Time Curve (0 to last) of DS-1040b was calculated using non-compartmental analysis.
Time Frame
Cohort 1: 0 up to 72 h post infusion; Cohorts 2 and 3: 0 up to 96 h post infusion; Cohort 4 and 5: 0 up to 120 h post infusion
Title
Pharmacokinetic Parameter Terminal Half-life Following Intravenous Infusion of DS-1040b Combined With Standard of Care Anti-coagulation Therapy in Participants With Acute Submassive Pulmonary Embolism
Description
Plasma concentrations at each time point and PK parameter Terminal Half-life of DS-1040b was calculated using non-compartmental analysis.
Time Frame
Cohort 1: 0 up to 72 h post infusion; Cohorts 2 and 3: 0 up to 96 h post infusion; Cohort 4 and 5: 0 up to 120 h post infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Study Leader
Organizational Affiliation
Daiichi Sankyo, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Pulmonary Associates of Mobile
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36608
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
University of California, San Diego (UCSD) Medical Center
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Intercoastal Medical Group
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34239
Country
United States
Facility Name
Northwestern Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Kentucky Medical Center
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Mayo Clinic - Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Mercury Street Medical
City
Butte
State/Province
Montana
ZIP/Postal Code
59701
Country
United States
Facility Name
Jacobi Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
NYU Radiology Associate
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Duke University Medical Center (DUMC)
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
The Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Capital Area Research
City
Camp Hill
State/Province
Pennsylvania
ZIP/Postal Code
17011
Country
United States
Facility Name
Temple University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
Medical University Graz
City
Graz
ZIP/Postal Code
8036
Country
Austria
Facility Name
Medical University Innsbruck
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
Facility Name
Medical University of Vienna
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
Universite Libre de Bruxelles (ULB) - Hopital Erasme
City
Bruxelles
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Cliniques Universitaires Saint-Luc
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
University Hospital Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
CHU de Brest - Hopital de la Cavale Blanche
City
Brest
ZIP/Postal Code
29609
Country
France
Facility Name
CHU Gabriel Montpied Clermont-Ferrand
City
Clermont-Ferrand
ZIP/Postal Code
63000
Country
France
Facility Name
CHU de Grenoble
City
La Tronche
ZIP/Postal Code
38700
Country
France
Facility Name
Hopital Europeen Georges Pompidou
City
Paris
ZIP/Postal Code
75017
Country
France
Facility Name
CHU St Etienne - Hopital Nord
City
Saint-étienne
ZIP/Postal Code
42055
Country
France
Facility Name
Hopital Civil de Strasbourg
City
Strasbourg
ZIP/Postal Code
67091
Country
France
Facility Name
Staedtisches Klinikum Dresden-Friedrichstadt
City
Dresden
ZIP/Postal Code
01067
Country
Germany
Facility Name
Universitaetsklinikum Dresden
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Universitaetsmedizin Greifswald
City
Greifswald
ZIP/Postal Code
17475
Country
Germany
Facility Name
Universitatsklinikum Magdeburg
City
Magdeburg
ZIP/Postal Code
39120
Country
Germany
Facility Name
Klinikum rechts der Isar, Technische Universität München
City
München
ZIP/Postal Code
81675
Country
Germany
Facility Name
AOU Ospedali Riuniti di Ancona
City
Ancona
ZIP/Postal Code
60126
Country
Italy
Facility Name
Universit degli Studi di Perugia - Azienda Ospedaliera di Perugia
City
Perugia
ZIP/Postal Code
06129
Country
Italy
Facility Name
Humanitas Research Hospital
City
Rozzano
ZIP/Postal Code
20089
Country
Italy
Facility Name
Ospedale di Circolo
City
Varese
ZIP/Postal Code
21100
Country
Italy
Facility Name
Noordwest Ziekenhuisgroep
City
Alkmaar
ZIP/Postal Code
1815 JD
Country
Netherlands
Facility Name
Academisch Medisch Centrum
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Albert Schweitzer Hospital
City
Dordrecht
ZIP/Postal Code
3318 AT
Country
Netherlands
Facility Name
Leiden University Medical Center - Leids Universitair Medisch Centrum (LUMC)
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
Facility Name
HagaZiekenhuis
City
The Hague
ZIP/Postal Code
2545 AA
Country
Netherlands
Facility Name
UMC Utrecht
City
Utrecht
ZIP/Postal Code
3584 CX
Country
Netherlands
Facility Name
Hospital Universitario
City
Girona
ZIP/Postal Code
17007
Country
Spain
Facility Name
Hospital Universitario Ramon y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital Clinico San Carlos
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hospital Virgen del Rocío
City
Sevilla
ZIP/Postal Code
41014
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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/
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing URL
https://vivli.org/ourmember/daiichi-sankyo/
Learn more about this trial
Study to Assess the Safety, Pharmacokinetics/Dynamics of DS-1040b in Subjects With Acute Submassive Pulmonary Embolism
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