Safety of DS-1040b in Acute Ischemic Stroke Patients Treated With Thrombectomy

Not Applicable

Completed

Conditions: Acute Ischemic Stroke

Interventions: Drug: DS1040b
Drug: Placebo

Registration Number: NCT03198715

Lead Sponsor: Daiichi Sankyo Co., Ltd.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 42

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
DS-1040b 4.8 mg	DS1040b	Participants receive DS-1040b 4.8 mg by intravenous infusion over six hours
DS-1040b 1.2 mg	DS1040b	Participants receive DS-1040b 1.2 mg by intravenous infusion over six hours
DS-1040b 0.6 mg	DS1040b	Participants receive DS-1040b 0.6 mg by intravenous infusion over six hours
DS-1040b 2.4 mg	DS1040b	Participants receive DS-1040b 2.4 mg by intravenous infusion over six hours
Placebo	Placebo	Participants receive saline by intravenous infusion over six hours

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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 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)
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.
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.

Trial Locations

Locations (20): Iwate Prefectural Central Hospital
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Morioka, Iwate, Japan
Nagasaki University Hospital
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Nagasaki, Japan
Japan Organization of Occupational Health and Safety Kansai Rosai Hospital
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Amagasaki, Hyogo, Japan
Yokohama Municipal Citizen's Hospital
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Yokohama, Kanagawa, Japan
National Cerebral and Cardiovascular Center
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Suita, Osaka, Japan
Funabashi Municipal Medical Center
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Funabashi, Chiba, Japan
Nakamura Memorial Hospital
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Sapporo, Hokkaido, Japan
Kobe City Medical Center General Hospital
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Kobe, Hyogo, Japan
Hirosaki University Hospital
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Hirosaki, Aomori, Japan
University of Tsukuba Hospital
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Tsukuba, Ibaraki, Japan
Kokura Memorial Hospital
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Kitakyushu, Fukuota, Japan
Mihara Memorial Hospital
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Isesaki, Gunma, Japan
Hyogo College of Medicine College Hospital
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Nishinomiya, Hyogo, Japan
Mie University Hospital
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Tsu, Mie, Japan
Seisho Hospital
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Odawara, Kanagawa, Japan
Saitama Medical University International Medical Center
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Hidaka, Saitama, Japan
Yamaguchi University Hospital
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Ube, Yamaguchi, Japan
Hiroshima City Hiroshima Citizens Hospital
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Hiroshima, Japan
Niigata City General Hospital
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Niigata, Japan
Wakayama Medical University Hospital
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Wakayama, Japan