Clinical trial NCT02923115: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pulmonary Embolism
Thrombotic Disease
Keywords: Venous thromboembolism (VTE)
Pulmonary embolism (PE)
Acute Submassive Pulmonary Embolism
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2016-10-04
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: 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
timeFrame: Baseline up to Day 30 post infusion, up to approximately 3 years 2 months
Secondary outcomes:
measure: 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
timeFrame: Baseline to 12-72 hours post start of infusion, up to approximately 3 years 2 months
measure: 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
timeFrame: Baseline to 12-72 hours post start of infusion, up to approximately 3 years 2 months
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Pulmonary Associates of Mobile
state: Alabama
city: Beverly Hills
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Diego
country: United States
facility: University of California, San Diego (UCSD) Medical Center
state: California
city: Sarasota
country: United States
facility: Intercoastal Medical Group
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Butte
country: United States
facility: Mercury Street Medical
state: Montana
city: Bronx
country: United States
facility: Jacobi Medical Center
state: New York
city: New York
country: United States
facility: NYU Radiology Associate
state: New York
city: Durham
country: United States
facility: Duke University Medical Center (DUMC)
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Camp Hill
country: United States
facility: Capital Area Research
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Graz
country: Austria
facility: Medical University Graz
city: Innsbruck
country: Austria
facility: Medical University Innsbruck
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Bruxelles
country: Belgium
facility: Universite Libre de Bruxelles (ULB) - Hopital Erasme
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: University Hospital Leuven
city: Brest
country: France
facility: CHU de Brest - Hopital de la Cavale Blanche
city: Clermont-Ferrand
country: France
facility: CHU Gabriel Montpied Clermont-Ferrand
city: La Tronche
country: France
facility: CHU de Grenoble
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Saint-étienne
country: France
facility: CHU St Etienne - Hopital Nord
city: Strasbourg
country: France
facility: Hopital Civil de Strasbourg
city: Dresden
country: Germany
facility: Staedtisches Klinikum Dresden-Friedrichstadt
city: Dresden
country: Germany
facility: Universitaetsklinikum Dresden
city: Greifswald
country: Germany
facility: Universitaetsmedizin Greifswald
city: Magdeburg
country: Germany
facility: Universitatsklinikum Magdeburg
city: München
country: Germany
facility: Klinikum rechts der Isar, Technische Universität München
city: Ancona
country: Italy
facility: AOU Ospedali Riuniti di Ancona
city: Perugia
country: Italy
facility: Universit degli Studi di Perugia - Azienda Ospedaliera di Perugia
city: Rozzano
country: Italy
facility: Humanitas Research Hospital
city: Varese
country: Italy
facility: Ospedale di Circolo
city: Alkmaar
country: Netherlands
facility: Noordwest Ziekenhuisgroep
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Hospital
city: Leiden
country: Netherlands
facility: Leiden University Medical Center - Leids Universitair Medisch Centrum (LUMC)
city: The Hague
country: Netherlands
facility: HagaZiekenhuis
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Girona
country: Spain
facility: Hospital Universitario
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocío
Study officials:
affiliation: Daiichi Sankyo
name: Clinical Study Leader
role: STUDY_DIRECTOR
References: