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

Phase 1

• Conditions: DS-1040b is an inhibitor of the activated form of thrombin-activatable fibrinolysis inhibitor (TAFIa) intended to be used for the treatment of thrombotic diseases including Pulmonary Embolism (PE); MedDRA version: 20.0 Level: PT Classification code 10037377 Term: Pulmonary embolism System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; MedDRA version: 20.0 Level: HLT Classification code 10037379 Term: Pulmonary embolism and thrombosis System Organ Class: 100000004866; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2015-005211-32-NL
• Lead Sponsor: Daiichi Sankyo, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-10-04
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 116

Inclusion Criteria

1. Male or female subjects, age 18 to 75 years and body weight between 50 and 130 kg, inclusive;
2. Subjects admitted to the hospital with a clinical diagnosis of acute PE with an onset of symptoms in the 5 days prior to diagnosis categorized as low risk or intermediate-risk or submassive PE and for whom catheter-based therapy is not planned;
a. Subjects must have a CTA scan confirming the PE diagnosis and with at least one measurable index lesion in a segmental or larger pulmonary artery prior to randomization;
b. Subjects should be in otherwise satisfactory health in the opinion of the Investigator;
c. Subjects may have concurrent DVT and have an inferior vena cava (IVC) filter placed prior to randomization;
d. Subjects may already be on SOC low molecular weight LMW heparin at the time of randomization but for no longer than 36 hours.
3. Able to provide written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 75

Exclusion Criteria

1. 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;
2. Subjects for whom use of a thrombolytic, either systemic or via catheter, is planned;
3. Subjects with PE lesions only in the sub-segmental or smaller arteries, which due to limitations of the imaging method may not be consistently identified and measured;
4. Subjects unable or unwilling to take the required SOC anticoagulation therapy;
5. Subjects receiving more than 36 hours of SOC anticoagulants for treatment of the index PE event prior to randomization. Study drug infusion will ideally begin within 6hr after randomization
6. Subjects who had prior intracranial hemorrhage, known arteriovenous malformation or aneurysm, or evidence of active bleeding;
7. Subjects with bleeding diathesis, a platelet count < 100,000, international normalized ratio (INR) > 1.7, or clinically significant elevated activated partial thromboplastin time (aPTT) that is not explained by use of LMW heparin;
8. Subjects with active endocarditis;
9. Subjects with < 6 month history of acute coronary syndrome (ACS) whether or not they have undergone percutaneous coronary intervention (PCI);
10. Subjects who require ongoing dual antiplatelet therapy or treatment with aspirin alone in a dosage of more than 100 mg/per day;
11. Chronic treatment with non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) including both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) inhibitors for = 4 days/week anticipated to continue during the study;
12. Subjects with uncontrolled hypertension at randomization, evidenced by systolic blood pressure > 180 mm Hg or diastolic blood pressure>120 mmHg, or who require parenteral medication to maintain blood pressure below these limits;
13. Subjects who within 3 months prior to randomization have had intracranial surgery, clinically significant head trauma (in the opinion of the Principal Investigator), a stroke, or have received thrombolytic treatment;
14. Subjects with ECG evidence of 2nd degree or higher atrioventricular (AV) block or with QTcB or QTcF >450 ms;
15. Subjects who within 21 days prior to randomization have had gastrointestinal or genitourinary bleeding;
16. Subjects who within 14 days prior to randomization have had major surgery or a lumbar puncture (or epidural steroid injection);
17. Subjects with hemoglobin < 10 g/dL;
18. Subjects with an estimated creatinine clearance < 60 mL/min;
19. Subjects with diagnosed active liver disease or with elevation of liver enzymes/bilirubin:
a. Alanine transaminase (ALT) or aspartate transaminase (AST) = 2 times upper limit of normal (ULN)
b. Total bilirubin (TBL) = 1.5 times ULN (except due to confirmed Gilbert’s syndrome)
20. Subjects with known history of testing positive for Hepatitis B antigen or Hepatitis C antibody before randomization;
21. Subjects with known history of testing positive for the human immunodeficienc

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified