Safety of DS-1040b in Acute Ischemic Stroke Patients Treated With Thrombectomy
- Conditions
- Acute Ischemic Stroke
- Interventions
- Drug: DS1040bDrug: 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
- 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
-
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:
- safety or well-being of the participant or their offspring
- safety of the study staff
- 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
🇯🇵Morioka, Iwate, Japan
Nagasaki University Hospital
🇯🇵Nagasaki, Japan
Japan Organization of Occupational Health and Safety Kansai Rosai Hospital
🇯🇵Amagasaki, Hyogo, Japan
Yokohama Municipal Citizen's Hospital
🇯🇵Yokohama, Kanagawa, Japan
National Cerebral and Cardiovascular Center
🇯🇵Suita, Osaka, Japan
Funabashi Municipal Medical Center
🇯🇵Funabashi, Chiba, Japan
Nakamura Memorial Hospital
🇯🇵Sapporo, Hokkaido, Japan
Kobe City Medical Center General Hospital
🇯🇵Kobe, Hyogo, Japan
Hirosaki University Hospital
🇯🇵Hirosaki, Aomori, Japan
University of Tsukuba Hospital
🇯🇵Tsukuba, Ibaraki, Japan
Kokura Memorial Hospital
🇯🇵Kitakyushu, Fukuota, Japan
Mihara Memorial Hospital
🇯🇵Isesaki, Gunma, Japan
Hyogo College of Medicine College Hospital
🇯🇵Nishinomiya, Hyogo, Japan
Mie University Hospital
🇯🇵Tsu, Mie, Japan
Seisho Hospital
🇯🇵Odawara, Kanagawa, Japan
Saitama Medical University International Medical Center
🇯🇵Hidaka, Saitama, Japan
Yamaguchi University Hospital
🇯🇵Ube, Yamaguchi, Japan
Hiroshima City Hiroshima Citizens Hospital
🇯🇵Hiroshima, Japan
Niigata City General Hospital
🇯🇵Niigata, Japan
Wakayama Medical University Hospital
🇯🇵Wakayama, Japan