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

Primary Purpose

Acute Ischemic Stroke

Status
Completed
Phase
Not Applicable
Locations
Japan
Study Type
Interventional
Intervention
DS1040b
Placebo
Sponsored by
Daiichi Sankyo Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Ischemic Stroke focused on measuring Fibrinolysis enhancer, TAFIa inhibitor, Developmental Phase I

Eligibility Criteria

20 Years - 89 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hirosaki University Hospital
  • Funabashi Municipal Medical Center
  • Kokura Memorial Hospital
  • Mihara Memorial Hospital
  • Nakamura Memorial Hospital
  • Japan Organization of Occupational Health and Safety Kansai Rosai Hospital
  • Kobe City Medical Center General Hospital
  • Hyogo College of Medicine College Hospital
  • University of Tsukuba Hospital
  • Iwate Prefectural Central Hospital
  • Seisho Hospital
  • Yokohama Municipal Citizen's Hospital
  • Mie University Hospital
  • National Cerebral and Cardiovascular Center
  • Saitama Medical University International Medical Center
  • Yamaguchi University Hospital
  • Hiroshima City Hiroshima Citizens Hospital
  • Nagasaki University Hospital
  • Niigata City General Hospital
  • Wakayama Medical University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

DS-1040b 0.6 mg

DS-1040b 1.2 mg

DS-1040b 2.4 mg

DS-1040b 4.8 mg

Placebo

Arm Description

Participants receive DS-1040b 0.6 mg by intravenous infusion over six hours

Participants receive DS-1040b 1.2 mg by intravenous infusion over six hours

Participants receive DS-1040b 2.4 mg by intravenous infusion over six hours

Participants receive DS-1040b 4.8 mg by intravenous infusion over six hours

Participants receive saline by intravenous infusion over six hours

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
Pharmacokinetic Analysis Maximum Concentration (Cmax) of DS-1040a in Plasma
The PK parameter of maximum concentration (Cmax) was observed values.
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.
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
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)
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.
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.
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.

Full Information

First Posted
June 19, 2017
Last Updated
January 7, 2021
Sponsor
Daiichi Sankyo Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT03198715
Brief Title
Safety of DS-1040b in Acute Ischemic Stroke Patients Treated With Thrombectomy
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.
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
July 30, 2017 (Actual)
Primary Completion Date
January 19, 2020 (Actual)
Study Completion Date
January 19, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Daiichi Sankyo Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Ischemic Stroke
Keywords
Fibrinolysis enhancer, TAFIa inhibitor, Developmental Phase I

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Masking
Participant
Allocation
Randomized
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
DS-1040b 0.6 mg
Arm Type
Experimental
Arm Description
Participants receive DS-1040b 0.6 mg by intravenous infusion over six hours
Arm Title
DS-1040b 1.2 mg
Arm Type
Experimental
Arm Description
Participants receive DS-1040b 1.2 mg by intravenous infusion over six hours
Arm Title
DS-1040b 2.4 mg
Arm Type
Experimental
Arm Description
Participants receive DS-1040b 2.4 mg by intravenous infusion over six hours
Arm Title
DS-1040b 4.8 mg
Arm Type
Experimental
Arm Description
Participants receive DS-1040b 4.8 mg by intravenous infusion over six hours
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants receive saline by intravenous infusion over six hours
Intervention Type
Drug
Intervention Name(s)
DS1040b
Other Intervention Name(s)
Investigational product
Intervention Description
DS-1040b in solution for intravenous infusion
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Saline solution
Intervention Description
Saline solution for intravenous infusion
Primary Outcome Measure Information:
Title
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
Description
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
Title
Number of Participants With Non-ICH Major Bleeding Within 96 Hours From Start of Treatment With DS-1040b In Acute Ischemic Stroke Participants
Description
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
Secondary Outcome Measure Information:
Title
Pharmacokinetic Analysis Area Under The Plasma Concentration Time Curve (AUC) of DS-1040a in Plasma
Description
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
Title
Pharmacokinetic Analysis Maximum Concentration (Cmax) of DS-1040a in Plasma
Description
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
Title
Pharmacokinetic Analysis Time to Maximum Concentration (Tmax) of DS-1040b in Plasma
Description
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
Title
Pharmacokinetic Analysis Terminal Half-Life (T1/2) of DS-1040b in Plasma
Description
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
Title
Pharmacokinetic Analysis Mean Amount of DS-1040a Excreted in Urine in Acute Ischemic Stroke Participants
Description
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
Title
Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants
Description
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
Title
Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants
Description
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
Title
Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
89 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: safety or well-being of the participant or their offspring safety of the study staff analysis of results
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Leader
Organizational Affiliation
Daiichi Sankyo, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Hirosaki University Hospital
City
Hirosaki
State/Province
Aomori
ZIP/Postal Code
036-8563
Country
Japan
Facility Name
Funabashi Municipal Medical Center
City
Funabashi
State/Province
Chiba
ZIP/Postal Code
273-8588
Country
Japan
Facility Name
Kokura Memorial Hospital
City
Kitakyushu
State/Province
Fukuota
ZIP/Postal Code
802-8555
Country
Japan
Facility Name
Mihara Memorial Hospital
City
Isesaki
State/Province
Gunma
ZIP/Postal Code
372-0006
Country
Japan
Facility Name
Nakamura Memorial Hospital
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
060-8570
Country
Japan
Facility Name
Japan Organization of Occupational Health and Safety Kansai Rosai Hospital
City
Amagasaki
State/Province
Hyogo
ZIP/Postal Code
660-8511
Country
Japan
Facility Name
Kobe City Medical Center General Hospital
City
Kobe
State/Province
Hyogo
ZIP/Postal Code
650-0046
Country
Japan
Facility Name
Hyogo College of Medicine College Hospital
City
Nishinomiya
State/Province
Hyogo
ZIP/Postal Code
663-8501
Country
Japan
Facility Name
University of Tsukuba Hospital
City
Tsukuba
State/Province
Ibaraki
ZIP/Postal Code
305-8576
Country
Japan
Facility Name
Iwate Prefectural Central Hospital
City
Morioka
State/Province
Iwate
ZIP/Postal Code
020-0066
Country
Japan
Facility Name
Seisho Hospital
City
Odawara
State/Province
Kanagawa
ZIP/Postal Code
250-0001
Country
Japan
Facility Name
Yokohama Municipal Citizen's Hospital
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
240-8555
Country
Japan
Facility Name
Mie University Hospital
City
Tsu
State/Province
Mie
ZIP/Postal Code
514-8507
Country
Japan
Facility Name
National Cerebral and Cardiovascular Center
City
Suita
State/Province
Osaka
ZIP/Postal Code
565-8565
Country
Japan
Facility Name
Saitama Medical University International Medical Center
City
Hidaka
State/Province
Saitama
ZIP/Postal Code
350-1298
Country
Japan
Facility Name
Yamaguchi University Hospital
City
Ube
State/Province
Yamaguchi
ZIP/Postal Code
755-8505
Country
Japan
Facility Name
Hiroshima City Hiroshima Citizens Hospital
City
Hiroshima
ZIP/Postal Code
730-8518
Country
Japan
Facility Name
Nagasaki University Hospital
City
Nagasaki
ZIP/Postal Code
852-8521
Country
Japan
Facility Name
Niigata City General Hospital
City
Niigata
ZIP/Postal Code
950-1197
Country
Japan
Facility Name
Wakayama Medical University Hospital
City
Wakayama
ZIP/Postal Code
641-8509
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35061236
Citation
Sakai N, Takeuchi M, Imamura H, Shimamura N, Yoshimura S, Naito H, Kimura N, Masuo O, Hirotsune N, Morita K, Toyoda K, Yamagami H, Ishihara H, Nakatsu T, Miyoshi N, Suda M, Fujimoto S. Safety, Pharmacokinetics and Pharmacodynamics of DS-1040, in Combination with Thrombectomy, in Japanese Patients with Acute Ischemic Stroke. Clin Drug Investig. 2022 Feb;42(2):137-149. doi: 10.1007/s40261-021-01112-8. Epub 2022 Jan 21.
Results Reference
derived

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

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