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

Acute Ischemic Stroke Clinical Trial

Official title:

A Phase I, Single Blind, Placebo-controlled, Randomized Study to Assess the Safety of DS-1040b in Subjects With Thrombectomy Treated Acute Ischemic Stroke.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03198715
• Other study ID #: DS1040-A-J110
• Secondary ID: 173612
• Status: Completed
• Phase: N/A
• Start date: July 30, 2017
• Est. completion date: January 19, 2020

Study information

• Verified date: January 2021
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: January 19, 2020
• Est. primary completion date: January 19, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 89 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Cerebral Infarction
• Ischemia
• Stroke

Intervention

Drug:
• DS1040b
DS-1040b in solution for intravenous infusion
• Placebo
Saline solution for intravenous infusion

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	From start of treatment up to 36 hours post single, intravenous dose
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.	From start of treatment up to 96 hours post single, intravenous dose
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.	Predose, 0.5 hours (h), 3 h, 6 h, 18 h, 24 h, 48 h, and 96 h post single, intravenous dose
Secondary	Pharmacokinetic Analysis Maximum Concentration (Cmax) of DS-1040a in Plasma	The PK parameter of maximum concentration (Cmax) was observed values.	Predose, 0.5 hours (h), 3 h, 6 h, 18 h, 24 h, 48 h, and 96 h post single, intravenous dose
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.	Predose, 0.5 hours (h), 3 h, 6 h, 18 h, 24 h, 48 h, and 96 h post single, intravenous dose
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	Predose, 0.5 hours (h), 3 h, 6 h, 18 h, 24 h, 48 h, and 96 h post single, intravenous dose
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)	From start of treatment up to 24 hours post single, intravenous dose
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.	Baseline, 6 hours and 24 hours post single, intravenous dose
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.	Baseline, 6 hours, 24 hours, and 48 hours post single, intravenous dose
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.	Baseline, 6 hours, 24 hours, and 48 hours post single, intravenous dose