Acute Ischemic Stroke
Conditions
Keywords
Fibrinolysis enhancer, TAFIa inhibitor, Developmental Phase I
Brief summary
The aim of this study is to find out if DS-1040b is safe and tolerable in acute ischemic stroke patients with thrombectomy. Four groups will receive different doses of DS-1040b by intravenous infusion for 6 hours. Groups with the lowest dose will start. When it is determined that each dose is safe and tolerable, the next higher dose will be given to the next group.
Interventions
DRUGDS1040b
DS-1040b in solution for intravenous infusion
DRUGPlacebo
Saline solution for intravenous infusion
Sponsors
Daiichi Sankyo Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
20 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
* Is an acute ischemic stroke patients with evidence of intracranial vascular occlusion * Is enrolled in principle within 8 hours of symptom onset * Has treatment plan that includes stent retriever * Has protocol-defined scores on several scales
Exclusion criteria
* Has treatment plan that includes fibrinolysis or fibinolysis * Has identified intracranial hemorrhage or subarachnoid hemorrhage * Has active bleeding like gastrointestinal hemorrhage * Has cerebral bleeding risk; intracranial tumor, brain aneurysm, cerebral arteriovenous malformation, or history of intracranial bleeding * Has severe hepatic or renal impairment * Has been a participant in other clinical trial within 30 days prior to treatment * Is pregnant, lactating, or planning on becoming pregnant during treatment period * Has any condition or history that might, per protocol or in the opinion of the investigator, compromise: 1. safety or well-being of the participant or their offspring 2. safety of the study staff 3. analysis of results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | From start of treatment up to 36 hours post single, intravenous dose | Symptomatic and asymptomatic intracranial hemorrhage (ICH) confirmed by head imaging (CT or MRI) are reported. Symptomatic ICH was defined as Intracranial hemorrhage with clinical deterioration causing an increase in the National Institutes of Health Stroke Scale (NIHSS) score of ≥ 4 points (defined by European Cooperative Acute Stroke Study). Asymptomatic ICH included the following: Hemorrhagic infarction type 1: Small petechial hemorrhage along the margins of the infarct, Hemorrhagic infarction type 2: Confluent petechial hemorrhage within the infarcted area, but without a mass effect, Parenchymal hematoma type 1: Hematoma involving ≤ 30% of the infarcted area with a slight mass effect, Parenchymal hematoma type 2: Hematoma involving \> 30% of, or outside the infarcted area, with a significant mass effect. |
| Number of Participants With Non-ICH Major Bleeding Within 96 Hours From Start of Treatment With DS-1040b In Acute Ischemic Stroke Participants | From start of treatment up to 96 hours post single, intravenous dose | Non-ICH was defined as a clinically evident bleeding with a 5 g/dL or greater decrease in hemoglobin. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Analysis Time to Maximum Concentration (Tmax) of DS-1040b in Plasma | Predose, 0.5 hours (h), 3 h, 6 h, 18 h, 24 h, 48 h, and 96 h post single, intravenous dose | The PK parameter of time to maximum concentration (Tmax) was observed values. When there are more than one time point, the time point when the concentration reached the first Cmax will be used as Tmax. |
| Pharmacokinetic Analysis Terminal Half-Life (T1/2) of DS-1040b in Plasma | Predose, 0.5 hours (h), 3 h, 6 h, 18 h, 24 h, 48 h, and 96 h post single, intravenous dose | The PK parameter of terminal half-life (T1/2) was calculated from the following formula in participants whose Kel could be calculated. T1/2=ln2 / Kel |
| Pharmacokinetic Analysis Mean Amount of DS-1040a Excreted in Urine in Acute Ischemic Stroke Participants | From start of treatment up to 24 hours post single, intravenous dose | The pharmacokinetic parameter of amount of drug excreted in urine was calculated from the following formula: urine concentration (ng/mL) /10\^6× (urine weight / urinary specific gravity) |
| Pharmacokinetic Analysis Area Under The Plasma Concentration Time Curve (AUC) of DS-1040a in Plasma | Predose, 0.5 hours (h), 3 h, 6 h, 18 h, 24 h, 48 h, and 96 h post single, intravenous dose | The pharmacokinetic (PK) parameter of area under the plasma concentration-time curve up to the last quantifiable time was calculated using linear up logarithmic down rule. |
| Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Baseline, 6 hours, 24 hours, and 48 hours post single, intravenous dose | Mean D-dimer levels and change from baseline in D-dimer levels are reported.Change from baseline is based on the number of subjects with baseline and at least one post-baseline laboratory test. |
| Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Baseline, 6 hours, 24 hours, and 48 hours post single, intravenous dose | Mean activated form of thrombin-activatable fibrinolysis inhibitor (TAFIa) and change from baseline in TAFIa are reported. Change from baseline is based on the number of subjects with baseline and at least one post-baseline laboratory test. |
| Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Baseline, 6 hours and 24 hours post single, intravenous dose | The mean thrombin activatable fibrinolysis (TAFI) antigen levels and change from baseline in TAFI levels are reported. Change from baseline is based on the number of participants with baseline and at least one post-baseline laboratory test. |
| Pharmacokinetic Analysis Maximum Concentration (Cmax) of DS-1040a in Plasma | Predose, 0.5 hours (h), 3 h, 6 h, 18 h, 24 h, 48 h, and 96 h post single, intravenous dose | The PK parameter of maximum concentration (Cmax) was observed values. |
Countries
Japan
Participant flow
Recruitment details
A total of 42 participants who met all inclusion criteria and no exclusion criteria were randomized to treatment. Of the 42 participants randomized, 41 participants received treatment.
Pre-assignment details
The study consisted of 4 parallel, ascending-dose cohorts. The DS-1040b 0.6 mg cohort only consisted of a DS-1040b group. A ratio of DS-1040b:placebo of 3:1 per cohort was used for the 1.2 mg and higher dose cohorts.
Participants by arm
| Arm | Count |
|---|---|
| DS-1040b 0.6 mg Participants who received a single, intravenous infusion of DS-1040b 0.6 mg. | 6 |
| DS-1040b 1.2 mg Participants who received a single, intravenous infusion of DS-1040b 1.2 mg. | 12 |
| DS-1040b 2.4 mg Participants who received a single, intravenous infusion of DS-1040b 2.4 mg. | 11 |
| DS-1040b 4.8 mg Participants who received a single, intravenous infusion of DS-1040b 4.8 mg. | 3 |
| Placebo Participants who received a single, intravenous infusion of placebo. | 9 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 | 0 | 2 |
| Overall Study | Other | 0 | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | DS-1040b 0.6 mg | DS-1040b 1.2 mg | DS-1040b 2.4 mg | DS-1040b 4.8 mg | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 11 Participants | 9 Participants | 2 Participants | 8 Participants | 35 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 6 Participants |
| Age, Continuous | 71.5 years STANDARD_DEVIATION 6.8 | 76.3 years STANDARD_DEVIATION 6.96 | 73.6 years STANDARD_DEVIATION 10.4 | 69.0 years STANDARD_DEVIATION 7.81 | 76.9 years STANDARD_DEVIATION 11.22 | 74.5 years STANDARD_DEVIATION 8.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 12 Participants | 11 Participants | 3 Participants | 9 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 12 Participants | 11 Participants | 3 Participants | 9 Participants | 41 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 6 participants | 12 participants | 11 participants | 3 participants | 9 participants | 41 participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 5 Participants | 2 Participants | 5 Participants | 19 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 6 Participants | 1 Participants | 4 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 12 | 1 / 11 | 0 / 3 | 2 / 9 |
| other Total, other adverse events | 5 / 6 | 10 / 12 | 10 / 11 | 2 / 3 | 8 / 9 |
| serious Total, serious adverse events | 0 / 6 | 2 / 12 | 2 / 11 | 0 / 3 | 1 / 9 |
Outcome results
Primary
Number of Participants With Non-ICH Major Bleeding Within 96 Hours From Start of Treatment With DS-1040b In Acute Ischemic Stroke Participants
Non-ICH was defined as a clinically evident bleeding with a 5 g/dL or greater decrease in hemoglobin.
Time frame: From start of treatment up to 96 hours post single, intravenous dose
Population: Bleeding events were assessed in the Safety Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DS-1040b 0.6 mg | Number of Participants With Non-ICH Major Bleeding Within 96 Hours From Start of Treatment With DS-1040b In Acute Ischemic Stroke Participants | 0 Participants |
| DS-1040b 1.2 mg | Number of Participants With Non-ICH Major Bleeding Within 96 Hours From Start of Treatment With DS-1040b In Acute Ischemic Stroke Participants | 0 Participants |
| DS-1040b 2.4 mg | Number of Participants With Non-ICH Major Bleeding Within 96 Hours From Start of Treatment With DS-1040b In Acute Ischemic Stroke Participants | 0 Participants |
| DS-1040b 4.8 mg | Number of Participants With Non-ICH Major Bleeding Within 96 Hours From Start of Treatment With DS-1040b In Acute Ischemic Stroke Participants | 0 Participants |
| Placebo | Number of Participants With Non-ICH Major Bleeding Within 96 Hours From Start of Treatment With DS-1040b In Acute Ischemic Stroke Participants | 0 Participants |
Primary
Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants
Symptomatic and asymptomatic intracranial hemorrhage (ICH) confirmed by head imaging (CT or MRI) are reported. Symptomatic ICH was defined as Intracranial hemorrhage with clinical deterioration causing an increase in the National Institutes of Health Stroke Scale (NIHSS) score of ≥ 4 points (defined by European Cooperative Acute Stroke Study). Asymptomatic ICH included the following: Hemorrhagic infarction type 1: Small petechial hemorrhage along the margins of the infarct, Hemorrhagic infarction type 2: Confluent petechial hemorrhage within the infarcted area, but without a mass effect, Parenchymal hematoma type 1: Hematoma involving ≤ 30% of the infarcted area with a slight mass effect, Parenchymal hematoma type 2: Hematoma involving \> 30% of, or outside the infarcted area, with a significant mass effect.
Time frame: From start of treatment up to 36 hours post single, intravenous dose
Population: Bleeding events were assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DS-1040b 0.6 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Symptomatic ICH | 0 Participants |
| DS-1040b 0.6 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Not applicable | 1 Participants |
| DS-1040b 0.6 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Parenchymal hematoma type 2 | 0 Participants |
| DS-1040b 0.6 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Hemorrhagic infarction type 1 | 0 Participants |
| DS-1040b 0.6 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Asymptomatic ICH | 2 Participants |
| DS-1040b 0.6 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Hemorrhagic infarction type 2 | 1 Participants |
| DS-1040b 0.6 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Parenchymal hematoma type 1 | 0 Participants |
| DS-1040b 1.2 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Parenchymal hematoma type 1 | 3 Participants |
| DS-1040b 1.2 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Hemorrhagic infarction type 2 | 1 Participants |
| DS-1040b 1.2 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Asymptomatic ICH | 5 Participants |
| DS-1040b 1.2 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Symptomatic ICH | 0 Participants |
| DS-1040b 1.2 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Parenchymal hematoma type 2 | 0 Participants |
| DS-1040b 1.2 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Hemorrhagic infarction type 1 | 1 Participants |
| DS-1040b 1.2 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Not applicable | 1 Participants |
| DS-1040b 2.4 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Hemorrhagic infarction type 2 | 1 Participants |
| DS-1040b 2.4 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Symptomatic ICH | 0 Participants |
| DS-1040b 2.4 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Asymptomatic ICH | 4 Participants |
| DS-1040b 2.4 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Hemorrhagic infarction type 1 | 0 Participants |
| DS-1040b 2.4 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Parenchymal hematoma type 1 | 0 Participants |
| DS-1040b 2.4 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Parenchymal hematoma type 2 | 2 Participants |
| DS-1040b 2.4 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Not applicable | 1 Participants |
| DS-1040b 4.8 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Hemorrhagic infarction type 1 | 0 Participants |
| DS-1040b 4.8 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Parenchymal hematoma type 1 | 1 Participants |
| DS-1040b 4.8 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Asymptomatic ICH | 1 Participants |
| DS-1040b 4.8 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Not applicable | 0 Participants |
| DS-1040b 4.8 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Parenchymal hematoma type 2 | 0 Participants |
| DS-1040b 4.8 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Symptomatic ICH | 0 Participants |
| DS-1040b 4.8 mg | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Hemorrhagic infarction type 2 | 0 Participants |
| Placebo | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Hemorrhagic infarction type 1 | 0 Participants |
| Placebo | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Not applicable | 1 Participants |
| Placebo | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Parenchymal hematoma type 2 | 0 Participants |
| Placebo | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Parenchymal hematoma type 1 | 0 Participants |
| Placebo | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Asymptomatic ICH | 1 Participants |
| Placebo | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Symptomatic ICH | 0 Participants |
| Placebo | Number of Participants With Symptomatic or Asymptomatic Intracranial Hemorrhage (ICH) Within 36 Hours From Start of Treatment With DS-1040b in Acute Ischemic Stroke Participants | Hemorrhagic infarction type 2 | 0 Participants |
Secondary
Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants
Mean activated form of thrombin-activatable fibrinolysis inhibitor (TAFIa) and change from baseline in TAFIa are reported. Change from baseline is based on the number of subjects with baseline and at least one post-baseline laboratory test.
Time frame: Baseline, 6 hours, 24 hours, and 48 hours post single, intravenous dose
Population: Pharmacodynamic parameters were assessed in the Pharmacodynamic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DS-1040b 0.6 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Baseline | 104.5 % of normal pooled plasma control | Standard Deviation 30.68 |
| DS-1040b 0.6 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 48 hours postdose | -13.3 % of normal pooled plasma control | Standard Deviation 9.99 |
| DS-1040b 0.6 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 24 hours postdose | -6.2 % of normal pooled plasma control | Standard Deviation 7.56 |
| DS-1040b 0.6 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | 24 hours postdose | 93.4 % of normal pooled plasma control | Standard Deviation 29.03 |
| DS-1040b 0.6 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | 6 hours postdose | 110.4 % of normal pooled plasma control | Standard Deviation 28.1 |
| DS-1040b 0.6 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | 48 hours postdose | 91.2 % of normal pooled plasma control | Standard Deviation 27.01 |
| DS-1040b 0.6 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 6 hours postdose | -1.4 % of normal pooled plasma control | Standard Deviation 11.04 |
| DS-1040b 1.2 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 6 hours postdose | -2.6 % of normal pooled plasma control | Standard Deviation 11.82 |
| DS-1040b 1.2 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | 48 hours postdose | 70.0 % of normal pooled plasma control | Standard Deviation 7.09 |
| DS-1040b 1.2 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | 6 hours postdose | 77.9 % of normal pooled plasma control | Standard Deviation 18.52 |
| DS-1040b 1.2 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Baseline | 81.8 % of normal pooled plasma control | Standard Deviation 17.67 |
| DS-1040b 1.2 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 24 hours postdose | -5.5 % of normal pooled plasma control | Standard Deviation 15.17 |
| DS-1040b 1.2 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | 24 hours postdose | 78.7 % of normal pooled plasma control | Standard Deviation 14.58 |
| DS-1040b 1.2 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 48 hours postdose | -6.9 % of normal pooled plasma control | Standard Deviation 11.46 |
| DS-1040b 2.4 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | 48 hours postdose | 84.7 % of normal pooled plasma control | Standard Deviation 17.5 |
| DS-1040b 2.4 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Baseline | 93.9 % of normal pooled plasma control | Standard Deviation 28.92 |
| DS-1040b 2.4 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | 6 hours postdose | 82.7 % of normal pooled plasma control | Standard Deviation 16.49 |
| DS-1040b 2.4 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | 24 hours postdose | 90.7 % of normal pooled plasma control | Standard Deviation 18.67 |
| DS-1040b 2.4 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 6 hours postdose | -14.6 % of normal pooled plasma control | Standard Deviation 16 |
| DS-1040b 2.4 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 24 hours postdose | -6.4 % of normal pooled plasma control | Standard Deviation 12.03 |
| DS-1040b 2.4 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 48 hours postdose | -11.0 % of normal pooled plasma control | Standard Deviation 10.92 |
| DS-1040b 4.8 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | 24 hours postdose | 91.7 % of normal pooled plasma control | Standard Deviation 7.51 |
| DS-1040b 4.8 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 6 hours postdose | -30.3 % of normal pooled plasma control | Standard Deviation 13.01 |
| DS-1040b 4.8 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | 6 hours postdose | 68.7 % of normal pooled plasma control | Standard Deviation 10.97 |
| DS-1040b 4.8 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 48 hours postdose | -10.3 % of normal pooled plasma control | Standard Deviation 13.61 |
| DS-1040b 4.8 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 24 hours postdose | -7.3 % of normal pooled plasma control | Standard Deviation 16.04 |
| DS-1040b 4.8 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Baseline | 99.0 % of normal pooled plasma control | Standard Deviation 8.54 |
| DS-1040b 4.8 mg | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | 48 hours postdose | 88.7 % of normal pooled plasma control | Standard Deviation 6.66 |
| Placebo | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | 24 hours postdose | 88.0 % of normal pooled plasma control | Standard Deviation 16 |
| Placebo | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 48 hours postdose | -1.1 % of normal pooled plasma control | Standard Deviation 13.95 |
| Placebo | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 24 hours postdose | 0.6 % of normal pooled plasma control | Standard Deviation 8 |
| Placebo | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 6 hours postdose | 8.0 % of normal pooled plasma control | Standard Deviation 13.24 |
| Placebo | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | 6 hours postdose | 95.5 % of normal pooled plasma control | Standard Deviation 21.63 |
| Placebo | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | Baseline | 88.7 % of normal pooled plasma control | Standard Deviation 18.99 |
| Placebo | Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants | 48 hours postdose | 87.6 % of normal pooled plasma control | Standard Deviation 13.96 |
Secondary
Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants
Mean D-dimer levels and change from baseline in D-dimer levels are reported.Change from baseline is based on the number of subjects with baseline and at least one post-baseline laboratory test.
Time frame: Baseline, 6 hours, 24 hours, and 48 hours post single, intravenous dose
Population: Pharmacodynamic parameters were assessed in the Pharmacodynamic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DS-1040b 0.6 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Baseline | 1.600 ug/mL FEU | Standard Deviation 2.8865 |
| DS-1040b 0.6 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 48 hours postdose | -0.693 ug/mL FEU | Standard Deviation 1.6989 |
| DS-1040b 0.6 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 24 hours postdose | -0.442 ug/mL FEU | Standard Deviation 1.2701 |
| DS-1040b 0.6 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 24 hours postdose | 1.158 ug/mL FEU | Standard Deviation 1.6216 |
| DS-1040b 0.6 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 6 hours postdose | 1.368 ug/mL FEU | Standard Deviation 2.1428 |
| DS-1040b 0.6 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 48 hours postdose | 0.907 ug/mL FEU | Standard Deviation 1.1908 |
| DS-1040b 0.6 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 6 hour postdose | -0.452 ug/mL FEU | Standard Deviation 1.0327 |
| DS-1040b 1.2 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 6 hour postdose | -0.008 ug/mL FEU | Standard Deviation 0.1091 |
| DS-1040b 1.2 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 48 hours postdose | 0.912 ug/mL FEU | Standard Deviation 0.5107 |
| DS-1040b 1.2 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 6 hours postdose | 0.717 ug/mL FEU | Standard Deviation 0.4899 |
| DS-1040b 1.2 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Baseline | 0.730 ug/mL FEU | Standard Deviation 0.4176 |
| DS-1040b 1.2 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 24 hours postdose | 0.217 ug/mL FEU | Standard Deviation 0.5241 |
| DS-1040b 1.2 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 24 hours postdose | 0.960 ug/mL FEU | Standard Deviation 0.7254 |
| DS-1040b 1.2 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 48 hours postdose | 0.163 ug/mL FEU | Standard Deviation 0.2431 |
| DS-1040b 2.4 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 48 hours postdose | 2.668 ug/mL FEU | Standard Deviation 6.0954 |
| DS-1040b 2.4 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Baseline | 2.423 ug/mL FEU | Standard Deviation 4.8964 |
| DS-1040b 2.4 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 6 hours postdose | 3.254 ug/mL FEU | Standard Deviation 6.3573 |
| DS-1040b 2.4 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 24 hours postdose | 2.879 ug/mL FEU | Standard Deviation 6.0571 |
| DS-1040b 2.4 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 6 hour postdose | 1.497 ug/mL FEU | Standard Deviation 2.6031 |
| DS-1040b 2.4 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 24 hours postdose | 1.180 ug/mL FEU | Standard Deviation 2.4023 |
| DS-1040b 2.4 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 48 hours postdose | 1.033 ug/mL FEU | Standard Deviation 2.4047 |
| DS-1040b 4.8 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 24 hours postdose | 1.067 ug/mL FEU | Standard Deviation 0.5235 |
| DS-1040b 4.8 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 6 hour postdose | 0.477 ug/mL FEU | Standard Deviation 0.5742 |
| DS-1040b 4.8 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 6 hours postdose | 1.090 ug/mL FEU | Standard Deviation 0.454 |
| DS-1040b 4.8 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 48 hours postdose | 0.673 ug/mL FEU | Standard Deviation 0.8559 |
| DS-1040b 4.8 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 24 hours postdose | 0.453 ug/mL FEU | Standard Deviation 0.6422 |
| DS-1040b 4.8 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Baseline | 0.613 ug/mL FEU | Standard Deviation 0.125 |
| DS-1040b 4.8 mg | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 48 hours postdose | 1.287 ug/mL FEU | Standard Deviation 0.7371 |
| Placebo | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 24 hours postdose | 3.731 ug/mL FEU | Standard Deviation 7.1964 |
| Placebo | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 48 hours postdose | 0.260 ug/mL FEU | Standard Deviation 0.47 |
| Placebo | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 24 hours postdose | 0.284 ug/mL FEU | Standard Deviation 0.4342 |
| Placebo | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 6 hour postdose | -0.023 ug/mL FEU | Standard Deviation 0.134 |
| Placebo | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 6 hours postdose | 3.436 ug/mL FEU | Standard Deviation 7.3095 |
| Placebo | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Baseline | 3.096 ug/mL FEU | Standard Deviation 6.8343 |
| Placebo | Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 48 hours postdose | 0.941 ug/mL FEU | Standard Deviation 0.5545 |
Secondary
Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants
The mean thrombin activatable fibrinolysis (TAFI) antigen levels and change from baseline in TAFI levels are reported. Change from baseline is based on the number of participants with baseline and at least one post-baseline laboratory test.
Time frame: Baseline, 6 hours and 24 hours post single, intravenous dose
Population: Pharmacodynamic parameters were assessed in the Pharmacodynamic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DS-1040b 0.6 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 6 hour postdose | -5.12 % of normal pooled plasma control | Standard Deviation 6.463 |
| DS-1040b 0.6 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Baseline | 99.17 % of normal pooled plasma control | Standard Deviation 25.527 |
| DS-1040b 0.6 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 24 hours postdose | -11.42 % of normal pooled plasma control | Standard Deviation 6.934 |
| DS-1040b 0.6 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 6 hours postdose | 94.05 % of normal pooled plasma control | Standard Deviation 22.09 |
| DS-1040b 0.6 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 24 hours postdose | 87.75 % of normal pooled plasma control | Standard Deviation 20.938 |
| DS-1040b 1.2 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 6 hour postdose | 1.69 % of normal pooled plasma control | Standard Deviation 5.077 |
| DS-1040b 1.2 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 24 hours postdose | 78.09 % of normal pooled plasma control | Standard Deviation 11.033 |
| DS-1040b 1.2 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 6 hours postdose | 81.37 % of normal pooled plasma control | Standard Deviation 11.358 |
| DS-1040b 1.2 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 24 hours postdose | -1.95 % of normal pooled plasma control | Standard Deviation 9.641 |
| DS-1040b 1.2 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Baseline | 80.05 % of normal pooled plasma control | Standard Deviation 9.101 |
| DS-1040b 2.4 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 24 hours postdose | 77.62 % of normal pooled plasma control | Standard Deviation 14.208 |
| DS-1040b 2.4 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Baseline | 79.56 % of normal pooled plasma control | Standard Deviation 19.553 |
| DS-1040b 2.4 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 6 hours postdose | 86.12 % of normal pooled plasma control | Standard Deviation 13.727 |
| DS-1040b 2.4 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 6 hour postdose | 1.28 % of normal pooled plasma control | Standard Deviation 8.551 |
| DS-1040b 2.4 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 24 hours postdose | -5.09 % of normal pooled plasma control | Standard Deviation 6.625 |
| DS-1040b 4.8 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 24 hours postdose | -9.20 % of normal pooled plasma control | Standard Deviation 6.07 |
| DS-1040b 4.8 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Baseline | 81.90 % of normal pooled plasma control | Standard Deviation 2.75 |
| DS-1040b 4.8 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 6 hour postdose | -0.67 % of normal pooled plasma control | Standard Deviation 4.202 |
| DS-1040b 4.8 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 24 hours postdose | 72.70 % of normal pooled plasma control | Standard Deviation 8.681 |
| DS-1040b 4.8 mg | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 6 hours postdose | 81.23 % of normal pooled plasma control | Standard Deviation 6.313 |
| Placebo | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 24 hours postdose | 79.11 % of normal pooled plasma control | Standard Deviation 13.051 |
| Placebo | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 6 hour postdose | -0.73 % of normal pooled plasma control | Standard Deviation 5.579 |
| Placebo | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Baseline | 88.28 % of normal pooled plasma control | Standard Deviation 17.157 |
| Placebo | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | Change from baseline to 24 hours postdose | -9.16 % of normal pooled plasma control | Standard Deviation 9.759 |
| Placebo | Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants | 6 hours postdose | 87.55 % of normal pooled plasma control | Standard Deviation 15.987 |
Secondary
Pharmacokinetic Analysis Area Under The Plasma Concentration Time Curve (AUC) of DS-1040a in Plasma
The pharmacokinetic (PK) parameter of area under the plasma concentration-time curve up to the last quantifiable time was calculated using linear up logarithmic down rule.
Time frame: Predose, 0.5 hours (h), 3 h, 6 h, 18 h, 24 h, 48 h, and 96 h post single, intravenous dose
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS-1040b 0.6 mg | Pharmacokinetic Analysis Area Under The Plasma Concentration Time Curve (AUC) of DS-1040a in Plasma | 111 ng*h/mL | Standard Deviation 45.5 |
| DS-1040b 1.2 mg | Pharmacokinetic Analysis Area Under The Plasma Concentration Time Curve (AUC) of DS-1040a in Plasma | 275 ng*h/mL | Standard Deviation 72.2 |
| DS-1040b 2.4 mg | Pharmacokinetic Analysis Area Under The Plasma Concentration Time Curve (AUC) of DS-1040a in Plasma | 570 ng*h/mL | Standard Deviation 230 |
| DS-1040b 4.8 mg | Pharmacokinetic Analysis Area Under The Plasma Concentration Time Curve (AUC) of DS-1040a in Plasma | 1550 ng*h/mL | Standard Deviation 962 |
Secondary
Pharmacokinetic Analysis Maximum Concentration (Cmax) of DS-1040a in Plasma
The PK parameter of maximum concentration (Cmax) was observed values.
Time frame: Predose, 0.5 hours (h), 3 h, 6 h, 18 h, 24 h, 48 h, and 96 h post single, intravenous dose
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS-1040b 0.6 mg | Pharmacokinetic Analysis Maximum Concentration (Cmax) of DS-1040a in Plasma | 17.2 ng/mL | Standard Deviation 6.25 |
| DS-1040b 1.2 mg | Pharmacokinetic Analysis Maximum Concentration (Cmax) of DS-1040a in Plasma | 29.7 ng/mL | Standard Deviation 7.5 |
| DS-1040b 2.4 mg | Pharmacokinetic Analysis Maximum Concentration (Cmax) of DS-1040a in Plasma | 60.6 ng/mL | Standard Deviation 11.8 |
| DS-1040b 4.8 mg | Pharmacokinetic Analysis Maximum Concentration (Cmax) of DS-1040a in Plasma | 141 ng/mL | Standard Deviation 61.7 |
Secondary
Pharmacokinetic Analysis Mean Amount of DS-1040a Excreted in Urine in Acute Ischemic Stroke Participants
The pharmacokinetic parameter of amount of drug excreted in urine was calculated from the following formula: urine concentration (ng/mL) /10\^6× (urine weight / urinary specific gravity)
Time frame: From start of treatment up to 24 hours post single, intravenous dose
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set in participants with available sample for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS-1040b 0.6 mg | Pharmacokinetic Analysis Mean Amount of DS-1040a Excreted in Urine in Acute Ischemic Stroke Participants | 0.420 mg | Standard Deviation 0.0308 |
| DS-1040b 1.2 mg | Pharmacokinetic Analysis Mean Amount of DS-1040a Excreted in Urine in Acute Ischemic Stroke Participants | 0.880 mg | Standard Deviation 0.0683 |
| DS-1040b 2.4 mg | Pharmacokinetic Analysis Mean Amount of DS-1040a Excreted in Urine in Acute Ischemic Stroke Participants | 1.49 mg | Standard Deviation 0.309 |
| DS-1040b 4.8 mg | Pharmacokinetic Analysis Mean Amount of DS-1040a Excreted in Urine in Acute Ischemic Stroke Participants | 3.45 mg | Standard Deviation 0.417 |
Secondary
Pharmacokinetic Analysis Terminal Half-Life (T1/2) of DS-1040b in Plasma
The PK parameter of terminal half-life (T1/2) was calculated from the following formula in participants whose Kel could be calculated. T1/2=ln2 / Kel
Time frame: Predose, 0.5 hours (h), 3 h, 6 h, 18 h, 24 h, 48 h, and 96 h post single, intravenous dose
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis set in participants with available sample for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS-1040b 0.6 mg | Pharmacokinetic Analysis Terminal Half-Life (T1/2) of DS-1040b in Plasma | 4.61 hours | — |
| DS-1040b 1.2 mg | Pharmacokinetic Analysis Terminal Half-Life (T1/2) of DS-1040b in Plasma | 16.8 hours | Standard Deviation 1.74 |
| DS-1040b 2.4 mg | Pharmacokinetic Analysis Terminal Half-Life (T1/2) of DS-1040b in Plasma | 19.5 hours | Standard Deviation 10.5 |
| DS-1040b 4.8 mg | Pharmacokinetic Analysis Terminal Half-Life (T1/2) of DS-1040b in Plasma | 29.7 hours | Standard Deviation 2.35 |
Secondary
Pharmacokinetic Analysis Time to Maximum Concentration (Tmax) of DS-1040b in Plasma
The PK parameter of time to maximum concentration (Tmax) was observed values. When there are more than one time point, the time point when the concentration reached the first Cmax will be used as Tmax.
Time frame: Predose, 0.5 hours (h), 3 h, 6 h, 18 h, 24 h, 48 h, and 96 h post single, intravenous dose
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DS-1040b 0.6 mg | Pharmacokinetic Analysis Time to Maximum Concentration (Tmax) of DS-1040b in Plasma | 2.21 hours | Standard Deviation 2.18 |
| DS-1040b 1.2 mg | Pharmacokinetic Analysis Time to Maximum Concentration (Tmax) of DS-1040b in Plasma | 4.67 hours | Standard Deviation 2.29 |
| DS-1040b 2.4 mg | Pharmacokinetic Analysis Time to Maximum Concentration (Tmax) of DS-1040b in Plasma | 5.11 hours | Standard Deviation 1.85 |
| DS-1040b 4.8 mg | Pharmacokinetic Analysis Time to Maximum Concentration (Tmax) of DS-1040b in Plasma | 5.96 hours | Standard Deviation 0.03 |