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

Daiichi Sankyo

Status and phase: Completed; Phase 2; Phase 1

Conditions: Pulmonary Embolism; Thrombotic Disease

Treatments: Drug: DS-1040b; Drug: Enoxaparin; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02923115

2015-005211-32 (EudraCT Number)

DS1040-B-U107

Details and patient eligibility

About

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.

Enrollment: 134 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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134 participants in 2 patient groups, including a placebo group

DS-1040b

Experimental group

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.

Treatment:

Drug: Enoxaparin

Drug: DS-1040b

Placebo

Placebo Comparator group

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.

Treatment:

Drug: Placebo

Drug: Enoxaparin