Acute Ischemic Stroke, Thrombotic Disease
Conditions
Keywords
Acute Ischemic Stroke, Thrombotic disease, DS-1040b
Brief summary
This is a Phase 1b/2, double-blind (study participants and Investigators), placebo-controlled, randomized, single-ascending dose, multi-center study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DS-1040b in participants with Acute Ischemic Stroke (AIS).
Interventions
DRUGDS-1040b
DS-1040b for IV infusion (0.6 mg to 9.6 mg) over 6-hour period
DRUGPlacebo
0.9% sodium chloride (placebo comparator) for IV infusion over 6-hour period
Sponsors
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has a clinical diagnosis of acute ischemic stroke (including lacunar stroke/infarct) supported by computed topography or magnetic resonance imaging to rule out alternative cause for presenting symptoms * Has onset of stroke symptoms within 4.5 to 12 hours before initiation of study drug administration - for subjects with a stroke upon waking, time of symptom onset is the last time the subject was known to be well * Has a NIHSS score of ≥ 2 (for Cohorts 1-5) and ≥ 5 (for Cohort 6) * Has Low dose heparin or low molecular weight heparin at a preventive dose are allowed from 24 hours after treatment start completion and after confirmation of no intracranial bleeding on the 24-hours repeat brain imaging. * Is a Cohort 6 participant who is treated or anticipated to be treated with intra-arterial therapy (IAT) for ischemic stroke at the time of randomization (for enrollment in the IAT subgroup) * Has given written informed consent to participate in the study prior to participating in any study-related procedures - depending on country-specific practice, written informed consent may be acceptable from legally authorized representative * Has given a separate written informed consent for collecting a blood sample for genotyping
Exclusion criteria
* Is a Cohort 1-5 participant who has been treated or is going to be treated with tissue plasminogen activator (tPA) and/or endovascular thrombectomy during current stroke * Is a Cohort 6 participant treated or anticipated to be treated with tPA during current stroke * Has evidence of intracranial hemorrhage on non-contrast computed tomography (CT/CAT) scan or magnetic resonance imaging (MRI) * Has symptoms of subarachnoid hemorrhage, even with normal imaging * Has an Alberta Stroke Program Early CT Score (ASPECTS) \<6 * Has prior non-traumatic intracranial hemorrhage (excluding microhemorrhages observed in imaging) * Has known arteriovenous malformation or aneurysm * Has evidence of active bleeding * Has platelet count less than 100,000 * Has International Normalized Ratio greater than 1.7 * Has used unfractionated heparin within 24 hours prior to treatment and has an elevated partial thromboplastin time * Has used a non-vitamin K antagonist oral anticoagulant such as dabigatran, rivaroxaban, apixaban, or other factor Xa inhibitors within 24 hours before treatment * Has used fondaparinux or low molecular weight heparin at an anticoagulation dose within 24 hours prior to treatment * Has anticipated use of an anticoagulation dose of heparin, or fondaparinux or low molecular weight heparin, or nonvitamin K antagonist oral anticoagulant such as dabigatran, rivaroxaban, apixaban, or other factor Xa inhibitors within 48 hours after completion of study drug treatment (low dose heparin or low molecular weight heparin at a preventive dose are allowed from 24 hours after treatment completion and after confirmation of no intracranial bleeding on the 24 hours repeat brain imaging. In Cohort 6, heparin treatment associated with IAT is allowed.) * Has blood pressure \> 185/110 mmHg, or requires aggressive medication to maintain blood pressure below this limit (routine medical treatment including IV drug treatment is allowed to lower the blood pressure below this limit) * Has had intracranial surgery, clinically significant head trauma (in the opinion of Principal Investigator), Alteplase treatment, or a previous stroke within 1 month * Has had major surgery within 14 days * Has had gastrointestinal or genitourinary bleeding in the last 21 days * Has had a lumbar puncture (or epidural steroid injection) within 14 days * Has had a preexisting disability classified by modified Rankin Scale (mRS) \> 2 * Has an estimated glomerular filtration rate \< 60 mL/min/1.73 m\^2 * Has baseline hemoglobin \< 10.5 g/dL * Has a positive pregnancy test * Is currently participating in another investigational study or has participated in an investigational drug study within 30 days or 5 half-lives of that investigational drug prior to administration of the study drug * Is an employee or an immediate family member of an employee of the Sponsor, the Contract Research Organization (CRO), or the Site * Has any other condition the investigator determines would preclude participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Baseline up to 90 days post last dose, up to 3 years 11 months | Treatment-emergent adverse event (TEAE) is defined as an adverse event that emerges during the treatment period (from first dose date until 30 days after the last dosing date), having been absent at predose; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pre-dose state, when the adverse event is continuous. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve From Zero to Last Quantifiable Concentration Sampling Point (AUClast) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | Predose, 0.5, 3, 6, 9, 12, 24, 48, 72, and 96 hours postdose | The PK parameter of Area Under the Concentration Versus Time Curve from Zero to Last Quantifiable Concentration Sampling Point of DS-1040b was calculated from the plasma concentrations of DS-1040b using non-compartmental analysis |
| Summary of Pharmacokinetic Parameter Terminal Half-life (t1/2) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | Pre-dose, 0.5, 3, 6, 9, 12, 24, 48, 72, and 96 hours post-dose | The PK parameter of Terminal Half-life of DS-1040b was calculated from the plasma concentrations of DS-1040b using non-compartmental analysis in patients with available sample for the analysis. |
| Summary of Pharmacokinetic (PK) Parameter Maximum (Peak) Observed Plasma Concentration (Cmax) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | Predose, 0.5, 3, 6, 9, 12, 24, 48, 72, and 96 hours postdose | The PK parameter of Maximum (Peak) Observed Plasma Concentration (Cmax) of DS-1040b was calculated from the plasma concentrations of DS-1040b using non-compartmental analysis |
| Summary of Changes From Baseline at Day 30 in National Institute of Health Stroke Scale (NIHSS) Score Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | 30 days post dose | The National Institute of Health Stroke Scale (NIHSS) quantifies stroke severity based on weighted evaluation findings. The score for each ability is a number between 0 and 4, with 0 being normal functioning and 4 being completely impaired. The patient's NIHSS score is calculated by adding the number for each element of the scale; 42 is the highest score possible. In the NIHSS, the higher the score indicates more impairment (worse outcome) in a stroke patient. |
| Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 to 2 Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Day 5 (baseline) and Day 90 post dose | The modified Rankin scale (mRS) is a commonly used disability scale derived from the Rankin scale that is used to measure the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The level of disability following a stroke is assessed via a scale from 0 to 6, where 0 is no symptoms at all and 6 indicates death. Higher scores indicate worse outcome. The percentage of participants with an mRS score of 0 to 2 at Day 5 (baseline) and Day 90 is being reported. |
| Summary of Activated Form of Thrombin-activatable Fibrinolysis Inhibitor (TAFIa) Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Baseline and 6 hours postdose | The enzymatic activity of thrombin-activatable fibrinolysis inhibitor was assessed using the Stago Coagulation Analyzer. |
Countries
Australia, Czechia, France, Germany, Italy, Slovakia, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
A total of 106 participants who met all inclusion criteria and no exclusion criteria were randomized to treatment at a total of 78 clinic sites (46 in Europe, 19 in the United States, 7 in Asia, 5 in Australia, and 1 in Canada). Of the 106 participants randomized, 101 participants received treatment.
Pre-assignment details
The study consisted of 6, sequential, ascending-dose cohorts. Participants were randomized to either DS-1040b or placebo in a 3:1 ratio.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: DS-1040b 0.6 mg Participants who received a single intravenous infusion of DS-1040b 0.6 mg. | 7 |
| Cohort 2: DS-1040b 1.2 mg Participants who received a single intravenous infusion of DS-1040b 1.2 mg. | 6 |
| Cohort 3: DS-1040b 2.4 mg Participants who received a single intravenous infusion of DS-1040b 2.4 mg. | 13 |
| Cohort 4: DS-1040b 4.8 mg Participants who received a single intravenous infusion of DS-1040b 4.8 mg. | 17 |
| Cohort 5: DS-1040b 7.2 mg Participants who received a single intravenous infusion of DS-1040b 7.2 mg. | 18 |
| Cohort 6: DS-1040b 9.6 mg Participants who received a single intravenous infusion of DS-1040b 9.6 mg. | 16 |
| Placebo Participants who received a single intravenous infusion of placebo. | 24 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 1 | 0 | 0 | 2 | 0 | 0 |
| Overall Study | Randomized but did not receive treatment | 0 | 1 | 0 | 0 | 0 | 2 | 2 |
Baseline characteristics
| Characteristic | Cohort 2: DS-1040b 1.2 mg | Cohort 3: DS-1040b 2.4 mg | Cohort 4: DS-1040b 4.8 mg | Cohort 5: DS-1040b 7.2 mg | Cohort 1: DS-1040b 0.6 mg | Cohort 6: DS-1040b 9.6 mg | Placebo | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 4 Participants | 7 Participants | 8 Participants | 4 Participants | 7 Participants | 10 Participants | 43 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 8 Participants | 8 Participants | 9 Participants | 2 Participants | 9 Participants | 13 Participants | 52 Participants |
| Age, Continuous | 68.2 years STANDARD_DEVIATION 10.2 | 62.7 years STANDARD_DEVIATION 9.7 | 69.1 years STANDARD_DEVIATION 11.1 | 65.8 years STANDARD_DEVIATION 11.7 | 68.2 years STANDARD_DEVIATION 7.8 | 64.8 years STANDARD_DEVIATION 12.8 | 62.2 years STANDARD_DEVIATION 12.3 | 65.2 years STANDARD_DEVIATION 11.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 4 Participants | 8 Participants | 0 Participants | 2 Participants | 3 Participants | 17 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 11 Participants | 11 Participants | 10 Participants | 6 Participants | 13 Participants | 17 Participants | 72 Participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 6 Participants | 8 Participants | 3 Participants | 6 Participants | 11 Participants | 41 Participants |
| Sex: Female, Male Male | 4 Participants | 8 Participants | 11 Participants | 10 Participants | 4 Participants | 10 Participants | 13 Participants | 60 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 1 / 6 | 0 / 13 | 0 / 17 | 2 / 18 | 0 / 16 | 3 / 77 | 0 / 24 |
| other Total, other adverse events | 5 / 7 | 5 / 6 | 10 / 13 | 15 / 17 | 14 / 18 | 14 / 16 | 63 / 77 | 18 / 24 |
| serious Total, serious adverse events | 1 / 7 | 4 / 6 | 0 / 13 | 1 / 17 | 2 / 18 | 2 / 16 | 10 / 77 | 4 / 24 |
Outcome results
Primary
Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke
Treatment-emergent adverse event (TEAE) is defined as an adverse event that emerges during the treatment period (from first dose date until 30 days after the last dosing date), having been absent at predose; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pre-dose state, when the adverse event is continuous.
Time frame: Baseline up to 90 days post last dose, up to 3 years 11 months
Population: Treatment-emergent adverse events were assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: DS-1040b 0.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Any TEAE | 5 Participants |
| Cohort 1: DS-1040b 0.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Pyrexia | 0 Participants |
| Cohort 1: DS-1040b 0.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hypertension | 0 Participants |
| Cohort 1: DS-1040b 0.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hypokalaemia | 1 Participants |
| Cohort 1: DS-1040b 0.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Thrombocytopenia | 0 Participants |
| Cohort 1: DS-1040b 0.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hyperglycaemia | 0 Participants |
| Cohort 1: DS-1040b 0.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Headache | 3 Participants |
| Cohort 1: DS-1040b 0.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Vomiting | 0 Participants |
| Cohort 1: DS-1040b 0.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Dyslipidaemia | 0 Participants |
| Cohort 1: DS-1040b 0.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Constipation | 1 Participants |
| Cohort 1: DS-1040b 0.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Anxiety | 0 Participants |
| Cohort 1: DS-1040b 0.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Vitamin B12 deficiency | 0 Participants |
| Cohort 1: DS-1040b 0.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Insomnia | 0 Participants |
| Cohort 2: DS-1040b 1.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Anxiety | 1 Participants |
| Cohort 2: DS-1040b 1.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hypertension | 0 Participants |
| Cohort 2: DS-1040b 1.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Any TEAE | 5 Participants |
| Cohort 2: DS-1040b 1.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Thrombocytopenia | 1 Participants |
| Cohort 2: DS-1040b 1.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Pyrexia | 0 Participants |
| Cohort 2: DS-1040b 1.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Vomiting | 1 Participants |
| Cohort 2: DS-1040b 1.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Vitamin B12 deficiency | 0 Participants |
| Cohort 2: DS-1040b 1.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Headache | 1 Participants |
| Cohort 2: DS-1040b 1.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Insomnia | 0 Participants |
| Cohort 2: DS-1040b 1.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hypokalaemia | 2 Participants |
| Cohort 2: DS-1040b 1.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Constipation | 2 Participants |
| Cohort 2: DS-1040b 1.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Dyslipidaemia | 0 Participants |
| Cohort 2: DS-1040b 1.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hyperglycaemia | 0 Participants |
| Cohort 3: DS-1040b 2.4 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Insomnia | 1 Participants |
| Cohort 3: DS-1040b 2.4 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Dyslipidaemia | 0 Participants |
| Cohort 3: DS-1040b 2.4 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hypokalaemia | 2 Participants |
| Cohort 3: DS-1040b 2.4 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Any TEAE | 10 Participants |
| Cohort 3: DS-1040b 2.4 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Vitamin B12 deficiency | 0 Participants |
| Cohort 3: DS-1040b 2.4 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Constipation | 3 Participants |
| Cohort 3: DS-1040b 2.4 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Pyrexia | 0 Participants |
| Cohort 3: DS-1040b 2.4 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hypertension | 1 Participants |
| Cohort 3: DS-1040b 2.4 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Vomiting | 0 Participants |
| Cohort 3: DS-1040b 2.4 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Anxiety | 0 Participants |
| Cohort 3: DS-1040b 2.4 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Headache | 2 Participants |
| Cohort 3: DS-1040b 2.4 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Thrombocytopenia | 0 Participants |
| Cohort 3: DS-1040b 2.4 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hyperglycaemia | 0 Participants |
| Cohort 4: DS-1040b 4.8 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Pyrexia | 1 Participants |
| Cohort 4: DS-1040b 4.8 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Any TEAE | 15 Participants |
| Cohort 4: DS-1040b 4.8 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Constipation | 1 Participants |
| Cohort 4: DS-1040b 4.8 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hypokalaemia | 0 Participants |
| Cohort 4: DS-1040b 4.8 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Anxiety | 0 Participants |
| Cohort 4: DS-1040b 4.8 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Dyslipidaemia | 0 Participants |
| Cohort 4: DS-1040b 4.8 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Vitamin B12 deficiency | 0 Participants |
| Cohort 4: DS-1040b 4.8 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Insomnia | 0 Participants |
| Cohort 4: DS-1040b 4.8 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Thrombocytopenia | 0 Participants |
| Cohort 4: DS-1040b 4.8 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hypertension | 3 Participants |
| Cohort 4: DS-1040b 4.8 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Headache | 2 Participants |
| Cohort 4: DS-1040b 4.8 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Vomiting | 0 Participants |
| Cohort 4: DS-1040b 4.8 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hyperglycaemia | 1 Participants |
| Cohort 5: DS-1040b 7.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hyperglycaemia | 1 Participants |
| Cohort 5: DS-1040b 7.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Any TEAE | 14 Participants |
| Cohort 5: DS-1040b 7.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hypokalaemia | 2 Participants |
| Cohort 5: DS-1040b 7.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Constipation | 5 Participants |
| Cohort 5: DS-1040b 7.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Insomnia | 1 Participants |
| Cohort 5: DS-1040b 7.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hypertension | 1 Participants |
| Cohort 5: DS-1040b 7.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Anxiety | 0 Participants |
| Cohort 5: DS-1040b 7.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Dyslipidaemia | 1 Participants |
| Cohort 5: DS-1040b 7.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Thrombocytopenia | 0 Participants |
| Cohort 5: DS-1040b 7.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Vomiting | 0 Participants |
| Cohort 5: DS-1040b 7.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Pyrexia | 0 Participants |
| Cohort 5: DS-1040b 7.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Vitamin B12 deficiency | 0 Participants |
| Cohort 5: DS-1040b 7.2 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Headache | 1 Participants |
| Cohort 6: DS-1040b 9.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hyperglycaemia | 0 Participants |
| Cohort 6: DS-1040b 9.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Any TEAE | 14 Participants |
| Cohort 6: DS-1040b 9.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Thrombocytopenia | 0 Participants |
| Cohort 6: DS-1040b 9.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Anxiety | 2 Participants |
| Cohort 6: DS-1040b 9.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hypertension | 0 Participants |
| Cohort 6: DS-1040b 9.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Vomiting | 0 Participants |
| Cohort 6: DS-1040b 9.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Insomnia | 3 Participants |
| Cohort 6: DS-1040b 9.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Headache | 4 Participants |
| Cohort 6: DS-1040b 9.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Pyrexia | 0 Participants |
| Cohort 6: DS-1040b 9.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Constipation | 2 Participants |
| Cohort 6: DS-1040b 9.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Vitamin B12 deficiency | 0 Participants |
| Cohort 6: DS-1040b 9.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hypokalaemia | 2 Participants |
| Cohort 6: DS-1040b 9.6 mg | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Dyslipidaemia | 1 Participants |
| All DS-1040b | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Vomiting | 1 Participants |
| All DS-1040b | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Insomnia | 5 Participants |
| All DS-1040b | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Any TEAE | 63 Participants |
| All DS-1040b | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Pyrexia | 1 Participants |
| All DS-1040b | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Constipation | 14 Participants |
| All DS-1040b | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hyperglycaemia | 2 Participants |
| All DS-1040b | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hypokalaemia | 9 Participants |
| All DS-1040b | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Anxiety | 3 Participants |
| All DS-1040b | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Headache | 13 Participants |
| All DS-1040b | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Dyslipidaemia | 2 Participants |
| All DS-1040b | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Thrombocytopenia | 1 Participants |
| All DS-1040b | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Vitamin B12 deficiency | 0 Participants |
| All DS-1040b | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hypertension | 5 Participants |
| Placebo | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Thrombocytopenia | 3 Participants |
| Placebo | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Vomiting | 3 Participants |
| Placebo | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Insomnia | 5 Participants |
| Placebo | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Anxiety | 3 Participants |
| Placebo | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Any TEAE | 18 Participants |
| Placebo | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Constipation | 5 Participants |
| Placebo | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hyperglycaemia | 3 Participants |
| Placebo | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Headache | 2 Participants |
| Placebo | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hypertension | 3 Participants |
| Placebo | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Pyrexia | 3 Participants |
| Placebo | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Dyslipidaemia | 3 Participants |
| Placebo | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Vitamin B12 deficiency | 3 Participants |
| Placebo | Summary of Treatment-Emergent Adverse Event Reported by >10% of Participants Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Hypokalaemia | 6 Participants |
Secondary
Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 to 2 Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke
The modified Rankin scale (mRS) is a commonly used disability scale derived from the Rankin scale that is used to measure the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The level of disability following a stroke is assessed via a scale from 0 to 6, where 0 is no symptoms at all and 6 indicates death. Higher scores indicate worse outcome. The percentage of participants with an mRS score of 0 to 2 at Day 5 (baseline) and Day 90 is being reported.
Time frame: Day 5 (baseline) and Day 90 post dose
Population: Modified Rankin scale scores were assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: DS-1040b 0.6 mg | Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 to 2 Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Day 5 | 66.7 percentage of participants |
| Cohort 1: DS-1040b 0.6 mg | Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 to 2 Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Day 90 | 85.7 percentage of participants |
| Cohort 2: DS-1040b 1.2 mg | Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 to 2 Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Day 5 | 40.0 percentage of participants |
| Cohort 2: DS-1040b 1.2 mg | Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 to 2 Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Day 90 | 60.0 percentage of participants |
| Cohort 3: DS-1040b 2.4 mg | Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 to 2 Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Day 5 | 76.9 percentage of participants |
| Cohort 3: DS-1040b 2.4 mg | Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 to 2 Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Day 90 | 76.9 percentage of participants |
| Cohort 4: DS-1040b 4.8 mg | Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 to 2 Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Day 5 | 82.4 percentage of participants |
| Cohort 4: DS-1040b 4.8 mg | Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 to 2 Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Day 90 | 82.4 percentage of participants |
| Cohort 5: DS-1040b 7.2 mg | Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 to 2 Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Day 5 | 72.2 percentage of participants |
| Cohort 5: DS-1040b 7.2 mg | Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 to 2 Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Day 90 | 93.8 percentage of participants |
| Cohort 6: DS-1040b 9.6 mg | Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 to 2 Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Day 5 | 53.3 percentage of participants |
| Cohort 6: DS-1040b 9.6 mg | Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 to 2 Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Day 90 | 68.8 percentage of participants |
| All DS-1040b | Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 to 2 Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Day 90 | 79.7 percentage of participants |
| All DS-1040b | Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 to 2 Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Day 5 | 68.9 percentage of participants |
| Placebo | Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 to 2 Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Day 5 | 54.2 percentage of participants |
| Placebo | Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 to 2 Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Day 90 | 75.0 percentage of participants |
Secondary
Summary of Activated Form of Thrombin-activatable Fibrinolysis Inhibitor (TAFIa) Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke
The enzymatic activity of thrombin-activatable fibrinolysis inhibitor was assessed using the Stago Coagulation Analyzer.
Time frame: Baseline and 6 hours postdose
Population: TAFIa activity was assessed in the Pharmacodynamic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: DS-1040b 0.6 mg | Summary of Activated Form of Thrombin-activatable Fibrinolysis Inhibitor (TAFIa) Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Baseline | 96.7 mean percentage of TAFIa activity | Standard Deviation 23.7 |
| Cohort 1: DS-1040b 0.6 mg | Summary of Activated Form of Thrombin-activatable Fibrinolysis Inhibitor (TAFIa) Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | 6 h postdose | 93.5 mean percentage of TAFIa activity | Standard Deviation 26.6 |
| Cohort 2: DS-1040b 1.2 mg | Summary of Activated Form of Thrombin-activatable Fibrinolysis Inhibitor (TAFIa) Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Baseline | 97.8 mean percentage of TAFIa activity | Standard Deviation 17.5 |
| Cohort 2: DS-1040b 1.2 mg | Summary of Activated Form of Thrombin-activatable Fibrinolysis Inhibitor (TAFIa) Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | 6 h postdose | 98.8 mean percentage of TAFIa activity | Standard Deviation 27.2 |
| Cohort 3: DS-1040b 2.4 mg | Summary of Activated Form of Thrombin-activatable Fibrinolysis Inhibitor (TAFIa) Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Baseline | 100.4 mean percentage of TAFIa activity | Standard Deviation 21.6 |
| Cohort 3: DS-1040b 2.4 mg | Summary of Activated Form of Thrombin-activatable Fibrinolysis Inhibitor (TAFIa) Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | 6 h postdose | 86.7 mean percentage of TAFIa activity | Standard Deviation 16.7 |
| Cohort 4: DS-1040b 4.8 mg | Summary of Activated Form of Thrombin-activatable Fibrinolysis Inhibitor (TAFIa) Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Baseline | 105.1 mean percentage of TAFIa activity | Standard Deviation 23.4 |
| Cohort 4: DS-1040b 4.8 mg | Summary of Activated Form of Thrombin-activatable Fibrinolysis Inhibitor (TAFIa) Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | 6 h postdose | 75.9 mean percentage of TAFIa activity | Standard Deviation 20.9 |
| Cohort 5: DS-1040b 7.2 mg | Summary of Activated Form of Thrombin-activatable Fibrinolysis Inhibitor (TAFIa) Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Baseline | 108.1 mean percentage of TAFIa activity | Standard Deviation 30.5 |
| Cohort 5: DS-1040b 7.2 mg | Summary of Activated Form of Thrombin-activatable Fibrinolysis Inhibitor (TAFIa) Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | 6 h postdose | 72.9 mean percentage of TAFIa activity | Standard Deviation 22.6 |
| Cohort 6: DS-1040b 9.6 mg | Summary of Activated Form of Thrombin-activatable Fibrinolysis Inhibitor (TAFIa) Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Baseline | 112.6 mean percentage of TAFIa activity | Standard Deviation 27.2 |
| Cohort 6: DS-1040b 9.6 mg | Summary of Activated Form of Thrombin-activatable Fibrinolysis Inhibitor (TAFIa) Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | 6 h postdose | 73.9 mean percentage of TAFIa activity | Standard Deviation 14.4 |
| All DS-1040b | Summary of Activated Form of Thrombin-activatable Fibrinolysis Inhibitor (TAFIa) Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | Baseline | 100.9 mean percentage of TAFIa activity | Standard Deviation 20.8 |
| All DS-1040b | Summary of Activated Form of Thrombin-activatable Fibrinolysis Inhibitor (TAFIa) Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | 6 h postdose | 104.1 mean percentage of TAFIa activity | Standard Deviation 24.7 |
Secondary
Summary of Changes From Baseline at Day 30 in National Institute of Health Stroke Scale (NIHSS) Score Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke
The National Institute of Health Stroke Scale (NIHSS) quantifies stroke severity based on weighted evaluation findings. The score for each ability is a number between 0 and 4, with 0 being normal functioning and 4 being completely impaired. The patient's NIHSS score is calculated by adding the number for each element of the scale; 42 is the highest score possible. In the NIHSS, the higher the score indicates more impairment (worse outcome) in a stroke patient.
Time frame: 30 days post dose
Population: NIHSS stroke scale scores were assessed in the Safety Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: DS-1040b 0.6 mg | Summary of Changes From Baseline at Day 30 in National Institute of Health Stroke Scale (NIHSS) Score Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | -3.7 units on a scale | Standard Deviation 2.21 |
| Cohort 2: DS-1040b 1.2 mg | Summary of Changes From Baseline at Day 30 in National Institute of Health Stroke Scale (NIHSS) Score Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | -3.0 units on a scale | Standard Deviation 2 |
| Cohort 3: DS-1040b 2.4 mg | Summary of Changes From Baseline at Day 30 in National Institute of Health Stroke Scale (NIHSS) Score Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | -3.5 units on a scale | Standard Deviation 1.71 |
| Cohort 4: DS-1040b 4.8 mg | Summary of Changes From Baseline at Day 30 in National Institute of Health Stroke Scale (NIHSS) Score Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | -2.06 units on a scale | Standard Deviation 1.06 |
| Cohort 5: DS-1040b 7.2 mg | Summary of Changes From Baseline at Day 30 in National Institute of Health Stroke Scale (NIHSS) Score Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | -3.4 units on a scale | Standard Deviation 2.7 |
| Cohort 6: DS-1040b 9.6 mg | Summary of Changes From Baseline at Day 30 in National Institute of Health Stroke Scale (NIHSS) Score Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | -6.2 units on a scale | Standard Deviation 3.08 |
| All DS-1040b | Summary of Changes From Baseline at Day 30 in National Institute of Health Stroke Scale (NIHSS) Score Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | -3.9 units on a scale | Standard Deviation 2.56 |
| Placebo | Summary of Changes From Baseline at Day 30 in National Institute of Health Stroke Scale (NIHSS) Score Following Ascending Doses of DS-1040b and a Placebo in Participants With Acute Ischemic Stroke | -3.6 units on a scale | Standard Deviation 4.27 |
Secondary
Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve From Zero to Last Quantifiable Concentration Sampling Point (AUClast) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke
The PK parameter of Area Under the Concentration Versus Time Curve from Zero to Last Quantifiable Concentration Sampling Point of DS-1040b was calculated from the plasma concentrations of DS-1040b using non-compartmental analysis
Time frame: Predose, 0.5, 3, 6, 9, 12, 24, 48, 72, and 96 hours postdose
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: DS-1040b 0.6 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve From Zero to Last Quantifiable Concentration Sampling Point (AUClast) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | 69.74 ng*h/mL | Standard Deviation 16.19 |
| Cohort 2: DS-1040b 1.2 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve From Zero to Last Quantifiable Concentration Sampling Point (AUClast) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | 219.83 ng*h/mL | Standard Deviation 95.16 |
| Cohort 3: DS-1040b 2.4 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve From Zero to Last Quantifiable Concentration Sampling Point (AUClast) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | 447.75 ng*h/mL | Standard Deviation 199.97 |
| Cohort 4: DS-1040b 4.8 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve From Zero to Last Quantifiable Concentration Sampling Point (AUClast) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | 2611.87 ng*h/mL | Standard Deviation 4471.65 |
| Cohort 5: DS-1040b 7.2 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve From Zero to Last Quantifiable Concentration Sampling Point (AUClast) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | 1489.21 ng*h/mL | Standard Deviation 460.78 |
| Cohort 6: DS-1040b 9.6 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve From Zero to Last Quantifiable Concentration Sampling Point (AUClast) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | 1700.24 ng*h/mL | Standard Deviation 346.43 |
Secondary
Summary of Pharmacokinetic Parameter Terminal Half-life (t1/2) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke
The PK parameter of Terminal Half-life of DS-1040b was calculated from the plasma concentrations of DS-1040b using non-compartmental analysis in patients with available sample for the analysis.
Time frame: Pre-dose, 0.5, 3, 6, 9, 12, 24, 48, 72, and 96 hours post-dose
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set, except for terminal half-life which was assessed in patients with available sample for the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: DS-1040b 0.6 mg | Summary of Pharmacokinetic Parameter Terminal Half-life (t1/2) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | 2.59 h | Standard Deviation 0.46 |
| Cohort 2: DS-1040b 1.2 mg | Summary of Pharmacokinetic Parameter Terminal Half-life (t1/2) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | 4.14 h | Standard Deviation 0.17 |
| Cohort 3: DS-1040b 2.4 mg | Summary of Pharmacokinetic Parameter Terminal Half-life (t1/2) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | 10.50 h | Standard Deviation 15.02 |
| Cohort 4: DS-1040b 4.8 mg | Summary of Pharmacokinetic Parameter Terminal Half-life (t1/2) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | 36.68 h | Standard Deviation 25.94 |
| Cohort 5: DS-1040b 7.2 mg | Summary of Pharmacokinetic Parameter Terminal Half-life (t1/2) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | 33.37 h | Standard Deviation 14.71 |
| Cohort 6: DS-1040b 9.6 mg | Summary of Pharmacokinetic Parameter Terminal Half-life (t1/2) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | 35.86 h | Standard Deviation 10.98 |
Secondary
Summary of Pharmacokinetic (PK) Parameter Maximum (Peak) Observed Plasma Concentration (Cmax) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke
The PK parameter of Maximum (Peak) Observed Plasma Concentration (Cmax) of DS-1040b was calculated from the plasma concentrations of DS-1040b using non-compartmental analysis
Time frame: Predose, 0.5, 3, 6, 9, 12, 24, 48, 72, and 96 hours postdose
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: DS-1040b 0.6 mg | Summary of Pharmacokinetic (PK) Parameter Maximum (Peak) Observed Plasma Concentration (Cmax) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | 10.09 ng/mL | Standard Deviation 3.26 |
| Cohort 2: DS-1040b 1.2 mg | Summary of Pharmacokinetic (PK) Parameter Maximum (Peak) Observed Plasma Concentration (Cmax) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | 26.95 ng/mL | Standard Deviation 9.39 |
| Cohort 3: DS-1040b 2.4 mg | Summary of Pharmacokinetic (PK) Parameter Maximum (Peak) Observed Plasma Concentration (Cmax) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | 61.28 ng/mL | Standard Deviation 35.67 |
| Cohort 4: DS-1040b 4.8 mg | Summary of Pharmacokinetic (PK) Parameter Maximum (Peak) Observed Plasma Concentration (Cmax) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | 729.76 ng/mL | Standard Deviation 1661.06 |
| Cohort 5: DS-1040b 7.2 mg | Summary of Pharmacokinetic (PK) Parameter Maximum (Peak) Observed Plasma Concentration (Cmax) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | 191.06 ng/mL | Standard Deviation 59.6 |
| Cohort 6: DS-1040b 9.6 mg | Summary of Pharmacokinetic (PK) Parameter Maximum (Peak) Observed Plasma Concentration (Cmax) of DS-1040b Following Ascending Doses in Participants With Acute Ischemic Stroke | 203.70 ng/mL | Standard Deviation 41.49 |