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

• Sponsor: Daiichi Sankyo, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02923115
• Collaborator: (none)
• Enrollment: 134
• Locations: 46
• Arms: 2
• Actual Duration (Months): 37.4
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Embolism; Thrombotic Disease	Drug: DS-1040b; Drug: Placebo; Drug: Enoxaparin	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 134 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jun 23, 2016
• Actual Primary Completion Date: Aug 5, 2019
• Actual Study Completion Date: Aug 5, 2019

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. 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 [Baseline up to Day 30 post infusion, up to approximately 3 years 2 months]

   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

1. 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 [Baseline to 12-72 hours post start of infusion, up to approximately 3 years 2 months]

   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.

2. 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 [Baseline to 12-72 hours post start of infusion, up to approximately 3 years 2 months]

   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.

3. 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 [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]

   Plasma concentrations at each time point and PK parameter Cmax of DS 1040b was calculated using non-compartmental analysis.

4. 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 [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]

   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.

5. 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 [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]

   Plasma concentrations at each time point and PK parameter Terminal Half-life of DS 1062b was calculated using non-compartmental analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pulmonary Associates of Mobile	Mobile	Alabama	United States	36608
2	Cedars-Sinai Medical Center	Beverly Hills	California	United States	90211
3	University of California, San Diego (UCSD) Medical Center	San Diego	California	United States	92103
4	Intercoastal Medical Group	Sarasota	Florida	United States	34239
5	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
6	University of Kentucky Medical Center	Lexington	Kentucky	United States	40536
7	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
8	Mayo Clinic - Rochester	Rochester	Minnesota	United States	55905
9	Mercury Street Medical	Butte	Montana	United States	59701
10	Jacobi Medical Center	Bronx	New York	United States	10461
11	NYU Radiology Associate	New York	New York	United States	10016
12	Duke University Medical Center (DUMC)	Durham	North Carolina	United States	27710
13	The Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
14	Capital Area Research	Camp Hill	Pennsylvania	United States	17011
15	Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
16	Medical University Graz	Graz		Austria	8036
17	Medical University Innsbruck	Innsbruck		Austria	6020
18	Medical University of Vienna	Vienna		Austria	1090
19	Universite Libre de Bruxelles (ULB) - Hopital Erasme	Bruxelles		Belgium	1070
20	Cliniques Universitaires Saint-Luc	Bruxelles		Belgium	1200
21	University Hospital Leuven	Leuven		Belgium	3000
22	CHU de Brest - Hopital de la Cavale Blanche	Brest		France	29609
23	CHU Gabriel Montpied Clermont-Ferrand	Clermont-Ferrand		France	63000
24	CHU de Grenoble	La Tronche		France	38700
25	Hopital Europeen Georges Pompidou	Paris		France	75017
26	CHU St Etienne - Hopital Nord	Saint-étienne		France	42055
27	Hopital Civil de Strasbourg	Strasbourg		France	67091
28	Staedtisches Klinikum Dresden-Friedrichstadt	Dresden		Germany	01067
29	Universitaetsklinikum Dresden	Dresden		Germany	01307
30	Universitaetsmedizin Greifswald	Greifswald		Germany	17475
31	Universitatsklinikum Magdeburg	Magdeburg		Germany	39120
32	Klinikum rechts der Isar, Technische Universität München	München		Germany	81675
33	AOU Ospedali Riuniti di Ancona	Ancona		Italy	60126
34	Universit degli Studi di Perugia - Azienda Ospedaliera di Perugia	Perugia		Italy	06129
35	Humanitas Research Hospital	Rozzano		Italy	20089
36	Ospedale di Circolo	Varese		Italy	21100
37	Noordwest Ziekenhuisgroep	Alkmaar		Netherlands	1815 JD
38	Academisch Medisch Centrum	Amsterdam		Netherlands	1105 AZ
39	Albert Schweitzer Hospital	Dordrecht		Netherlands	3318 AT
40	Leiden University Medical Center - Leids Universitair Medisch Centrum (LUMC)	Leiden		Netherlands	2333 ZA
41	HagaZiekenhuis	The Hague		Netherlands	2545 AA
42	UMC Utrecht	Utrecht		Netherlands	3584 CX
43	Hospital Universitario	Girona		Spain	17007
44	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
45	Hospital Clinico San Carlos	Madrid		Spain	28040
46	Hospital Virgen del Rocío	Sevilla		Spain	41014

Sponsors and Collaborators

• Daiichi Sankyo, Inc.

Investigators

• Study Director: Clinical Study Leader, Daiichi Sankyo, Inc.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 21, 2016

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT02923115
• Other Study ID Numbers: DS1040-B-U107; 2015-005211-32
• First Posted: Oct 4, 2016
• Last Update Posted: Jul 30, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Daiichi Sankyo, Inc.: Venous thromboembolism (VTE); Pulmonary embolism (PE); Acute Submassive Pulmonary Embolism
• Additional relevant MeSH terms: Pulmonary Embolism; Embolism; Enoxaparin

Study Results

Participant Flow

Recruitment Details	A total of 134 participants who met all inclusion and no exclusion criteria were enrolled in the study at 47 clinic sites (15 in the United States and 32 in Europe). Of the 134 participants randomized to treatment, 125 received treatment.
Pre-assignment Detail	This study enrolled up to 5 sequential, ascending-dose, continuous infusion cohorts (starting DS1040b dose 20 mg). In Cohorts 1 and 2, eligible participants were randomized in a 2:1 ratio to either DS-1040b or placebo. Starting with Cohort 3, the ratio changed to 3:1. All participants received standard of care enoxaparin during study drug infusion.

Arm/Group Title	Cohort 1: DS-1040b 20 mg	Cohort 2: DS-1040b 40 mg	Cohort 3: DS-1040b 60 mg	Cohort 4: DS-1040b 80 mg	Cohort 5: DS-1040b 40 mg	Placebo
Arm/Group Description	Participants who received an intravenous infusion of 20 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 40 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 60 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 80 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 40 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of placebo in addition to standard of care anticoagulation therapy.
Period Title: Overall Study
STARTED	12	16	23	23	22	38
Treated	12	16	20	22	17	38
COMPLETED	12	15	20	21	17	38
NOT COMPLETED	0	1	3	2	5	0

Baseline Characteristics

Arm/Group Title	Cohort 1: DS-1040b 20 mg	Cohort 2: DS-1040b 40 mg	Cohort 3: DS-1040b 60 mg	Cohort 4: DS-1040b 80 mg	Cohort 5: DS-1040b 40 mg	Placebo	Total
Arm/Group Description	Participants who received an intravenous infusion of 20 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 40 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 60 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 80 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 40 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of placebo in addition to standard of care anticoagulation therapy.	Total of all reporting groups
Overall Participants	12	16	20	22	17	38	125
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	8 66.7%	7 43.8%	12 60%	15 68.2%	14 82.4%	23 60.5%	79 63.2%
>=65 years	4 33.3%	9 56.3%	8 40%	7 31.8%	3 17.6%	15 39.5%	46 36.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.1 (16.3)	62.1 (10.9)	55.1 (17.5)	55.0 (13.5)	56.5 (9.8)	58.3 (10.7)	57.2 (13.0)
Sex: Female, Male (Count of Participants)
Female	4 33.3%	8 50%	4 20%	7 31.8%	5 29.4%	12 31.6%	40 32%
Male	8 66.7%	8 50%	16 80%	15 68.2%	12 70.6%	26 68.4%	85 68%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	1 5%	0 0%	1 5.9%	3 7.9%	5 4%
White	12 100%	15 93.8%	19 95%	22 100%	16 94.1%	34 89.5%	118 94.4%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	1 2.6%	1 0.8%
Unknown or Not Reported	0 0%	1 6.3%	0 0%	0 0%	0 0%	0 0%	1 0.8%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Adjudicated bleeding events were assessed in the Safety Analysis Set.

Arm/Group Title	Cohort 1: DS-1040b 20 mg	Cohort 2: DS-1040b 40 mg	Cohort 3: DS-1040b 60 mg	Cohort 4: DS-1040b 80 mg	Cohort 5: DS-1040b 40 mg	Placebo
Arm/Group Description	Participants who received an intravenous infusion of 20 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 40 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 60 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 80 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 40 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of placebo in addition to standard of care anticoagulation therapy.
Measure Participants	12	16	20	22	17	38
At least 1 bleeding event	4 33.3%	3 18.8%	3 15%	4 18.2%	1 5.9%	10 26.3%
Major bleeding event	0 0%	0 0%	0 0%	1 4.5%	0 0%	0 0%
Non-major clinically relevant bleeding event	0 0%	0 0%	0 0%	2 9.1%	1 5.9%	1 2.6%
Minor or nuisance bleeding event	3 25%	2 12.5%	3 15%	2 9.1%	0 0%	6 15.8%
Fatal bleeding event	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Bleeding with Hb drop ≥2g/dL, transfusion ≥2 units	0 0%	0 0%	0 0%	1 4.5%	0 0%	0 0%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Changes in total thrombus volume were assessed in the Efficacy Analysis Set.

Arm/Group Title	Cohort 1: DS-1040b 20 mg	Cohort 2: DS-1040b 40 mg	Cohort 3: DS-1040b 60 mg	Cohort 4: DS-1040b 80 mg	Cohort 5: DS-1040b 40 mg	Placebo
Arm/Group Description	Participants who received an intravenous infusion of 20 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 40 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 60 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 80 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 40 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of placebo in addition to standard of care anticoagulation therapy.
Measure Participants	11	15	20	22	16	36
Mean (Standard Deviation) [percent change]	-23.78 (24.49)	-38.67 (17.34)	-33.50 (17.41)	-37.36 (26.90)	-32.33 (19.03)	-31.35 (17.74)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Reductions in total thrombus volume were assessed in the Efficacy Analysis Set.

Arm/Group Title	Cohort 1: DS-1040b 20 mg	Cohort 2: DS-1040b 40 mg	Cohort 3: DS-1040b 60 mg	Cohort 4: DS-1040b 80 mg	Cohort 5: DS-1040b 40 mg	Placebo
Arm/Group Description	Participants who received an intravenous infusion of 20 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 40 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 60 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 80 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 40 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of placebo in addition to standard of care anticoagulation therapy.
Measure Participants	12	15	20	22	17	38
No change or increase	2 16.7%	0 0%	1 5%	0 0%	1 5.9%	3 7.9%
<20% reduction	2 16.7%	3 18.8%	3 15%	5 22.7%	3 17.6%	5 13.2%
≥20% reduction	7 58.3%	12 75%	16 80%	17 77.3%	12 70.6%	28 73.7%
Missing data	1 8.3%	0 0%	0 0%	0 0%	1 5.9%	2 5.3%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.

Arm/Group Title	Cohort 1: DS-1040b 20 mg	Cohort 2: DS-1040b 40 mg	Cohort 3: DS-1040b 60 mg	Cohort 4: DS-1040b 80 mg	Cohort 5: DS-1040b 40 mg
Arm/Group Description	Participants who received an intravenous infusion of 20 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 40 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 60 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 80 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 40 mg DS-1040b in addition to standard of care anticoagulation therapy.
Measure Participants	11	15	19	22	17
Mean (Standard Deviation) [ng/mL]	970.09 (1373.43)	421.73 (515.57)	608.84 (562.94)	1006.41 (1883.49)	526.12 (535.03)

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.

Arm/Group Title	Cohort 1: DS-1040b 20 mg	Cohort 2: DS-1040b 40 mg	Cohort 3: DS-1040b 60 mg	Cohort 4: DS-1040b 80 mg	Cohort 5: DS-1040b 40 mg
Arm/Group Description	Participants who received an intravenous infusion of 20 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 40 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 60 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 80 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 40 mg DS-1040b in addition to standard of care anticoagulation therapy.
Measure Participants	11	15	19	22	17
Mean (Standard Deviation) [ng*h/mL]	5532.92 (4090.34)	7819.53 (2870.13)	13403.15 (8047.13)	17147.27 (15024.61)	8014.73 (2870.19)

6. Secondary Outcome

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 1062b 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

Outcome Measure Data

Analysis Population Description

Terminal half-life was assessed in patients with available data in the Pharmacokinetic Analysis Set.

Arm/Group Title	Cohort 1: DS-1040b 20 mg	Cohort 2: DS-1040b 40 mg	Cohort 3: DS-1040b 60 mg	Cohort 4: DS-1040b 80 mg	Cohort 5: DS-1040b 40 mg
Arm/Group Description	Participants who received an intravenous infusion of 20 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 40 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 60 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 80 mg DS-1040b in addition to standard of care anticoagulation therapy.	Participants who received an intravenous infusion of 40 mg DS-1040b in addition to standard of care anticoagulation therapy.
Measure Participants	9	13	18	5	9
Mean (Standard Deviation) [hours]	22.81 (3.13)	28.44 (5.75)	29.06 (7.60)	36.39 (2.07)	30.06 (3.45)

Adverse Events

Time Frame	Treatment-emergent adverse events (TEAEs) were collected from baseline up to Day 30 post infusion, up to approximately 3 years 2 months.
Adverse Event Reporting Description	A TEAE is defined as an adverse event that emerges during treatment, having been absent pretreatment, or worsening relative to the pre-treatment state.
Arm/Group Title	Cohort 1: DS-1040b 20 mg		Cohort 2: DS-1040b 40 mg		Cohort 3: DS-1040b 60 mg		Cohort 4: DS-1040b 80 mg		Cohort 5: DS-1040b 40 mg		Placebo
Arm/Group Description	Participants who received an intravenous infusion of 20 mg DS-1040b in addition to standard of care anticoagulation therapy.		Participants who received an intravenous infusion of 40 mg DS-1040b in addition to standard of care anticoagulation therapy.		Participants who received an intravenous infusion of 60 mg DS-1040b in addition to standard of care anticoagulation therapy.		Participants who received an intravenous infusion of 80 mg DS-1040b in addition to standard of care anticoagulation therapy.		Participants who received an intravenous infusion of 40 mg DS-1040b in addition to standard of care anticoagulation therapy.		Participants who received an intravenous infusion of placebo in addition to standard of care anticoagulation therapy.
All Cause Mortality
	Cohort 1: DS-1040b 20 mg		Cohort 2: DS-1040b 40 mg		Cohort 3: DS-1040b 60 mg		Cohort 4: DS-1040b 80 mg		Cohort 5: DS-1040b 40 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Serious Adverse Events
	Cohort 1: DS-1040b 20 mg		Cohort 2: DS-1040b 40 mg		Cohort 3: DS-1040b 60 mg		Cohort 4: DS-1040b 80 mg		Cohort 5: DS-1040b 40 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/12 (25%)		0/16 (0%)		2/20 (10%)		1/22 (4.5%)		3/17 (17.6%)		5/38 (13.2%)
Cardiac disorders
Sinus tachycardia	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Hepatobiliary disorders
Hepatocellular injury	1/12 (8.3%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Infections and infestations
Lung infection	1/12 (8.3%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Anal abscess	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Pneumonia	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		1/17 (5.9%)		0/38 (0%)
Infection	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Metastases to peritoneum	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Colon neoplasm	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Metastases to nervous system	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Testicular cancer metastatic	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Nervous system disorders
Presyncope	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Psychiatric disorders
Depression	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		1/17 (5.9%)		1/38 (2.6%)
Reproductive system and breast disorders
Endometrial hyperplasia	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary infarction	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Pulmonary embolism	1/12 (8.3%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Pleural effusion	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		1/17 (5.9%)		0/38 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1: DS-1040b 20 mg		Cohort 2: DS-1040b 40 mg		Cohort 3: DS-1040b 60 mg		Cohort 4: DS-1040b 80 mg		Cohort 5: DS-1040b 40 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/12 (66.7%)		6/16 (37.5%)		13/20 (65%)		10/22 (45.5%)		8/17 (47.1%)		25/38 (65.8%)
Blood and lymphatic system disorders
Anaemia	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Microcytic anaemia	1/12 (8.3%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Cardiac disorders
Atrial fibrillation	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		1/17 (5.9%)		0/38 (0%)
Bundle branch block right	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		1/17 (5.9%)		0/38 (0%)
Right ventricular dysfunction	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Sinus tachycardia	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Ear and labyrinth disorders
Tinnitus	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Vertigo	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Eye disorders
Vision blurred	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Gastrointestinal disorders
Diarrhoea	2/12 (16.7%)		1/16 (6.3%)		2/20 (10%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Constipation	0/12 (0%)		0/16 (0%)		2/20 (10%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Abdominal discomfort	0/12 (0%)		1/16 (6.3%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Nausea	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Vomiting	0/12 (0%)		0/16 (0%)		2/20 (10%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Abdominal distension	0/12 (0%)		1/16 (6.3%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Abdominal pain	0/12 (0%)		1/16 (6.3%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Anal haemorrhage	1/12 (8.3%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Faeces discoloured	0/12 (0%)		1/16 (6.3%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Paraesthesia oral	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
General disorders
Non-cardiac chest pain	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		2/38 (5.3%)
Chest pain	0/12 (0%)		1/16 (6.3%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Infusion site phlebitis	1/12 (8.3%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Malaise	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Peripheral swelling	0/12 (0%)		1/16 (6.3%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Pyrexia	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		1/17 (5.9%)		0/38 (0%)
Feeling cold	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Feeling hot	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Infusion site extravasation	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Vessel puncture site haematoma	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Hepatobiliary disorders
Hepatocellular injury	1/12 (8.3%)		1/16 (6.3%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Hypertransaminasaemia	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		1/38 (2.6%)
Infections and infestations
Lung infection	1/12 (8.3%)		0/16 (0%)		2/20 (10%)		0/22 (0%)		0/17 (0%)		2/38 (5.3%)
Urinary tract infection	0/12 (0%)		1/16 (6.3%)		2/20 (10%)		0/22 (0%)		0/17 (0%)		2/38 (5.3%)
Pneumonia	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		2/17 (11.8%)		0/38 (0%)
Respiratory tract infection	0/12 (0%)		0/16 (0%)		2/20 (10%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Anal abscess	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Appendicitis	0/12 (0%)		1/16 (6.3%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Oral fungal infection	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		1/17 (5.9%)		0/38 (0%)
Abscess limb	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Bacteriuria	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Infection	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Injury, poisoning and procedural complications
Urinary retention postoperative	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Clavicle fracture	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Skin abrasion	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Synovial rupture	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Investigations
Electrocardiogram QT prolonged	1/12 (8.3%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Liver function test increased	1/12 (8.3%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Blood pressure increased	1/12 (8.3%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Electrocardiogram abnormal	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Aspartate aminotransferase increased	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		1/38 (2.6%)
Crystal urine present	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Electrocardiogram ST segment abnormal	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Electrocardiogram T wave inversion	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Mean cell volume increased	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Occult blood positive	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Urobilinogen urine increased	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Metabolism and nutrition disorders
Hypokalaemia	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		1/17 (5.9%)		1/38 (2.6%)
Folate deficiency	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		1/17 (5.9%)		0/38 (0%)
Hyperphosphataemia	1/12 (8.3%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		2/38 (5.3%)
Pain in extremity	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		2/38 (5.3%)
Arthritis	0/12 (0%)		1/16 (6.3%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Muscle contracture	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		1/17 (5.9%)		0/38 (0%)
Back pain	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Bursitis	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Groin pain	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Musculoskeletal discomfort	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Spinal pain	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to nervous system	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Testicular cancer metastatic	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Nervous system disorders
Headache	1/12 (8.3%)		0/16 (0%)		3/20 (15%)		2/22 (9.1%)		0/17 (0%)		0/38 (0%)
Dizziness	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Migraine	1/12 (8.3%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Haemorrhage intracranial	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Presyncope	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Lethargy	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Muscle spasticity	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Tremor	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Psychiatric disorders
Anxiety	0/12 (0%)		0/16 (0%)		2/20 (10%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Depression	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		1/17 (5.9%)		1/38 (2.6%)
Delirium	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Renal and urinary disorders
Haematuria	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Dysuria	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Ketonuria	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Proteinuria	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Urine abnormality	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Reproductive system and breast disorders
Vaginal haemorrhage	1/12 (8.3%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Gynaecomastia	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		1/17 (5.9%)		0/38 (0%)
Endometrial hyperplasia	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	2/12 (16.7%)		2/16 (12.5%)		2/20 (10%)		0/22 (0%)		0/17 (0%)		3/38 (7.9%)
Haemoptysis	0/12 (0%)		0/16 (0%)		1/20 (5%)		1/22 (4.5%)		1/17 (5.9%)		3/38 (7.9%)
Pleural effusion	1/12 (8.3%)		0/16 (0%)		2/20 (10%)		0/22 (0%)		1/17 (5.9%)		2/38 (5.3%)
Pulmonary infarction	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		1/17 (5.9%)		1/38 (2.6%)
Dyspnoea	0/12 (0%)		1/16 (6.3%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Cough	1/12 (8.3%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Hyperventilation	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Pleurisy	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		1/17 (5.9%)		0/38 (0%)
Pulmonary embolism	1/12 (8.3%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Skin and subcutaneous tissue disorders
Rash	1/12 (8.3%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Ecchymosis	1/12 (8.3%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Night sweats	0/12 (0%)		0/16 (0%)		0/20 (0%)		1/22 (4.5%)		0/17 (0%)		0/38 (0%)
Surgical and medical procedures
Sinus operation	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Vascular disorders
Deep vein thrombosis	2/12 (16.7%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)
Circulatory collapse	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		1/17 (5.9%)		0/38 (0%)
Hypertension	0/12 (0%)		0/16 (0%)		1/20 (5%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Hypotension	0/12 (0%)		1/16 (6.3%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		0/38 (0%)
Haemorrhage	0/12 (0%)		0/16 (0%)		0/20 (0%)		0/22 (0%)		0/17 (0%)		1/38 (2.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.