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

Purpose

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

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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.
  • Drug: DS-1040b
    Single, continuous intravenous infusion over 12 to 24 hours (depending on cohort)
  • Drug: Enoxaparin
    Subcutaneous injection 1 mg/kg twice daily
Placebo Comparator
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.
  • Drug: Placebo
    Single, continuous intravenous infusion of 0.9% sodium chloride over 12 to 24 hours
  • Drug: Enoxaparin
    Subcutaneous injection 1 mg/kg twice daily

More Details

Status
Completed
Sponsor
Daiichi Sankyo

Study Contact