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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02923115
Recruitment Status : Completed
First Posted : October 4, 2016
Results First Posted : July 30, 2020
Last Update Posted : July 30, 2020
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Pulmonary Embolism
Thrombotic Disease
Interventions Drug: DS-1040b
Drug: Placebo
Drug: Enoxaparin
Enrollment 134
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 Details 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
Hide 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 [1] 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
Reason Not Completed
Lost to Follow-up             0             0             0             1             0             0
Withdrawal by Subject             0             1             0             0             0             0
Randomized, but not dosed             0             0             3             1             5             0
[1]
Randomized
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
Hide 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 Number of Baseline Participants 12 16 20 22 17 38 125
Hide Baseline Analysis Population Description
Demographic and baseline characteristics were assessed in the Safety Population.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 16 participants 20 participants 22 participants 17 participants 38 participants 125 participants
<=18 years
0
   0.0%
0
   0.0%
0
   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
  60.0%
15
  68.2%
14
  82.4%
23
  60.5%
79
  63.2%
>=65 years
4
  33.3%
9
  56.3%
8
  40.0%
7
  31.8%
3
  17.6%
15
  39.5%
46
  36.8%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 16 participants 20 participants 22 participants 17 participants 38 participants 125 participants
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  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 16 participants 20 participants 22 participants 17 participants 38 participants 125 participants
Female
4
  33.3%
8
  50.0%
4
  20.0%
7
  31.8%
5
  29.4%
12
  31.6%
40
  32.0%
Male
8
  66.7%
8
  50.0%
16
  80.0%
15
  68.2%
12
  70.6%
26
  68.4%
85
  68.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 16 participants 20 participants 22 participants 17 participants 38 participants 125 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   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
   0.0%
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
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
1
   5.0%
0
   0.0%
1
   5.9%
3
   7.9%
5
   4.0%
White
12
 100.0%
15
  93.8%
19
  95.0%
22
 100.0%
16
  94.1%
34
  89.5%
118
  94.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.6%
1
   0.8%
Unknown or Not Reported
0
   0.0%
1
   6.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.8%
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 12 16 20 22 17 38
Measure Type: Count of Participants
Unit of Measure: Participants
At least 1 bleeding event
4
  33.3%
3
  18.8%
3
  15.0%
4
  18.2%
1
   5.9%
10
  26.3%
Major bleeding event
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.5%
0
   0.0%
0
   0.0%
Non-major clinically relevant bleeding event
0
   0.0%
0
   0.0%
0
   0.0%
2
   9.1%
1
   5.9%
1
   2.6%
Minor or nuisance bleeding event
3
  25.0%
2
  12.5%
3
  15.0%
2
   9.1%
0
   0.0%
6
  15.8%
Fatal bleeding event
0
   0.0%
0
   0.0%
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%
0
   0.0%
1
   4.5%
0
   0.0%
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 11 15 20 22 16 36
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 12 15 20 22 17 38
Measure Type: Count of Participants
Unit of Measure: Participants
No change or increase
2
  16.7%
0
   0.0%
1
   5.0%
0
   0.0%
1
   5.9%
3
   7.9%
<20% reduction
2
  16.7%
3
  20.0%
3
  15.0%
5
  22.7%
3
  17.6%
5
  13.2%
≥20% reduction
7
  58.3%
12
  80.0%
16
  80.0%
17
  77.3%
12
  70.6%
28
  73.7%
Missing data
1
   8.3%
0
   0.0%
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 11 15 19 22 17
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 11 15 19 22 17
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 9 13 18 5 9
Mean (Standard Deviation)
Unit of Measure: hours
22.81  (3.13) 28.44  (5.75) 29.06  (7.60) 36.39  (2.07) 30.06  (3.45)
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
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/12 (0.00%)   0/16 (0.00%)   0/20 (0.00%)   0/22 (0.00%)   0/17 (0.00%)   0/38 (0.00%) 
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/12 (25.00%)   0/16 (0.00%)   2/20 (10.00%)   1/22 (4.55%)   3/17 (17.65%)   5/38 (13.16%) 
Cardiac disorders             
Sinus tachycardia  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Hepatobiliary disorders             
Hepatocellular injury  1  1/12 (8.33%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Infections and infestations             
Lung infection  1  1/12 (8.33%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Anal abscess  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Pneumonia  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/38 (0.00%) 
Infection  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Metastases to liver  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Metastases to peritoneum  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Colon neoplasm  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Metastases to nervous system  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Testicular cancer metastatic  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Nervous system disorders             
Presyncope  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Psychiatric disorders             
Depression  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  1/38 (2.63%) 
Reproductive system and breast disorders             
Endometrial hyperplasia  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Pulmonary infarction  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Pulmonary embolism  1  1/12 (8.33%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Pleural effusion  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/38 (0.00%) 
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/12 (66.67%)   6/16 (37.50%)   13/20 (65.00%)   10/22 (45.45%)   8/17 (47.06%)   25/38 (65.79%) 
Blood and lymphatic system disorders             
Anaemia  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Microcytic anaemia  1  1/12 (8.33%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Cardiac disorders             
Atrial fibrillation  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/38 (0.00%) 
Bundle branch block right  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/38 (0.00%) 
Right ventricular dysfunction  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Sinus tachycardia  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Ear and labyrinth disorders             
Tinnitus  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Vertigo  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Eye disorders             
Vision blurred  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Gastrointestinal disorders             
Diarrhoea  1  2/12 (16.67%)  1/16 (6.25%)  2/20 (10.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Constipation  1  0/12 (0.00%)  0/16 (0.00%)  2/20 (10.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Abdominal discomfort  1  0/12 (0.00%)  1/16 (6.25%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Nausea  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Vomiting  1  0/12 (0.00%)  0/16 (0.00%)  2/20 (10.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Abdominal distension  1  0/12 (0.00%)  1/16 (6.25%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Abdominal pain  1  0/12 (0.00%)  1/16 (6.25%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Anal haemorrhage  1  1/12 (8.33%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Faeces discoloured  1  0/12 (0.00%)  1/16 (6.25%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Paraesthesia oral  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
General disorders             
Non-cardiac chest pain  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  2/38 (5.26%) 
Chest pain  1  0/12 (0.00%)  1/16 (6.25%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Infusion site phlebitis  1  1/12 (8.33%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Malaise  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Peripheral swelling  1  0/12 (0.00%)  1/16 (6.25%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Pyrexia  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/38 (0.00%) 
Feeling cold  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Feeling hot  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Infusion site extravasation  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Vessel puncture site haematoma  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Hepatobiliary disorders             
Hepatocellular injury  1  1/12 (8.33%)  1/16 (6.25%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Hypertransaminasaemia  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  1/38 (2.63%) 
Infections and infestations             
Lung infection  1  1/12 (8.33%)  0/16 (0.00%)  2/20 (10.00%)  0/22 (0.00%)  0/17 (0.00%)  2/38 (5.26%) 
Urinary tract infection  1  0/12 (0.00%)  1/16 (6.25%)  2/20 (10.00%)  0/22 (0.00%)  0/17 (0.00%)  2/38 (5.26%) 
Pneumonia  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  2/17 (11.76%)  0/38 (0.00%) 
Respiratory tract infection  1  0/12 (0.00%)  0/16 (0.00%)  2/20 (10.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Anal abscess  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Appendicitis  1  0/12 (0.00%)  1/16 (6.25%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Oral fungal infection  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/38 (0.00%) 
Abscess limb  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Bacteriuria  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Infection  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Injury, poisoning and procedural complications             
Urinary retention postoperative  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Clavicle fracture  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Skin abrasion  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Synovial rupture  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Investigations             
Electrocardiogram QT prolonged  1  1/12 (8.33%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Liver function test increased  1  1/12 (8.33%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Blood pressure increased  1  1/12 (8.33%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Electrocardiogram abnormal  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Aspartate aminotransferase increased  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  1/38 (2.63%) 
Crystal urine present  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Electrocardiogram ST segment abnormal  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Electrocardiogram T wave inversion  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Mean cell volume increased  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Occult blood positive  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Urobilinogen urine increased  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Metabolism and nutrition disorders             
Hypokalaemia  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  1/38 (2.63%) 
Folate deficiency  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/38 (0.00%) 
Hyperphosphataemia  1  1/12 (8.33%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Musculoskeletal and connective tissue disorders             
Arthralgia  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  2/38 (5.26%) 
Pain in extremity  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  2/38 (5.26%) 
Arthritis  1  0/12 (0.00%)  1/16 (6.25%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Muscle contracture  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/38 (0.00%) 
Back pain  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Bursitis  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Groin pain  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Musculoskeletal discomfort  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Spinal pain  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Metastases to nervous system  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Testicular cancer metastatic  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Nervous system disorders             
Headache  1  1/12 (8.33%)  0/16 (0.00%)  3/20 (15.00%)  2/22 (9.09%)  0/17 (0.00%)  0/38 (0.00%) 
Dizziness  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Migraine  1  1/12 (8.33%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Haemorrhage intracranial  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Presyncope  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Lethargy  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Muscle spasticity  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Tremor  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Psychiatric disorders             
Anxiety  1  0/12 (0.00%)  0/16 (0.00%)  2/20 (10.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Depression  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  1/38 (2.63%) 
Delirium  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Renal and urinary disorders             
Haematuria  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Dysuria  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Ketonuria  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Proteinuria  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Urine abnormality  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Reproductive system and breast disorders             
Vaginal haemorrhage  1  1/12 (8.33%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Gynaecomastia  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/38 (0.00%) 
Endometrial hyperplasia  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Epistaxis  1  2/12 (16.67%)  2/16 (12.50%)  2/20 (10.00%)  0/22 (0.00%)  0/17 (0.00%)  3/38 (7.89%) 
Haemoptysis  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  1/22 (4.55%)  1/17 (5.88%)  3/38 (7.89%) 
Pleural effusion  1  1/12 (8.33%)  0/16 (0.00%)  2/20 (10.00%)  0/22 (0.00%)  1/17 (5.88%)  2/38 (5.26%) 
Pulmonary infarction  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  1/17 (5.88%)  1/38 (2.63%) 
Dyspnoea  1  0/12 (0.00%)  1/16 (6.25%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Cough  1  1/12 (8.33%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Hyperventilation  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Pleurisy  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/38 (0.00%) 
Pulmonary embolism  1  1/12 (8.33%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Skin and subcutaneous tissue disorders             
Rash  1  1/12 (8.33%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Ecchymosis  1  1/12 (8.33%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Night sweats  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  0/38 (0.00%) 
Surgical and medical procedures             
Sinus operation  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Vascular disorders             
Deep vein thrombosis  1  2/12 (16.67%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
Circulatory collapse  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/38 (0.00%) 
Hypertension  1  0/12 (0.00%)  0/16 (0.00%)  1/20 (5.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Hypotension  1  0/12 (0.00%)  1/16 (6.25%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/38 (0.00%) 
Haemorrhage  1  0/12 (0.00%)  0/16 (0.00%)  0/20 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/38 (2.63%) 
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Contact for Clinical Trial Information
Organization: Daiichi Sankyo
Phone: 908-992-6400
EMail: CTRinfo@dsi.com
Layout table for additonal information
Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT02923115    
Other Study ID Numbers: DS1040-B-U107
2015-005211-32 ( EudraCT Number )
First Submitted: September 30, 2016
First Posted: October 4, 2016
Results First Submitted: June 17, 2020
Results First Posted: July 30, 2020
Last Update Posted: July 30, 2020