Clinical trial NCT03198715: 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
Overall status: COMPLETED
Phase: NA
Conditions: Acute Ischemic Stroke
Keywords: Fibrinolysis enhancer
TAFIa inhibitor
Developmental Phase I
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2017-06-26
Enrollment: 42
Sex: ALL
Minimum age (years): 20
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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:

  1. safety or well-being of the participant or their offspring
  2. safety of the study staff
  3. analysis of results

Primary outcomes:
measure: 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
timeFrame: From start of treatment up to 36 hours post single, intravenous dose
measure: Number of Participants With Non-ICH Major Bleeding Within 96 Hours From Start of Treatment With DS-1040b In Acute Ischemic Stroke Participants
timeFrame: From start of treatment up to 96 hours post single, intravenous dose
Secondary outcomes:
measure: Pharmacokinetic Analysis Area Under The Plasma Concentration Time Curve (AUC) of DS-1040a in Plasma
timeFrame: Predose, 0.5 hours (h), 3 h, 6 h, 18 h, 24 h, 48 h, and 96 h post single, intravenous dose
measure: Pharmacokinetic Analysis Maximum Concentration (Cmax) of DS-1040a in Plasma
timeFrame: Predose, 0.5 hours (h), 3 h, 6 h, 18 h, 24 h, 48 h, and 96 h post single, intravenous dose
measure: Pharmacokinetic Analysis Time to Maximum Concentration (Tmax) of DS-1040b in Plasma
timeFrame: Predose, 0.5 hours (h), 3 h, 6 h, 18 h, 24 h, 48 h, and 96 h post single, intravenous dose
measure: Pharmacokinetic Analysis Terminal Half-Life (T1/2) of DS-1040b in Plasma
timeFrame: Predose, 0.5 hours (h), 3 h, 6 h, 18 h, 24 h, 48 h, and 96 h post single, intravenous dose
measure: Pharmacokinetic Analysis Mean Amount of DS-1040a Excreted in Urine in Acute Ischemic Stroke Participants
timeFrame: From start of treatment up to 24 hours post single, intravenous dose
measure: Pharmacodynamic Analysis Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Antigen Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants
timeFrame: Baseline, 6 hours and 24 hours post single, intravenous dose
measure: Pharmacodynamic Analysis D-dimer Levels in Plasma and Change From Baseline in Acute Ischemic Stroke Participants
timeFrame: Baseline, 6 hours, 24 hours, and 48 hours post single, intravenous dose
measure: Pharmacodynamic Analysis Activated Form of Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa) Activity and Change From Baseline in Acute Ischemic Stroke Participants
timeFrame: Baseline, 6 hours, 24 hours, and 48 hours post single, intravenous dose
Other outcomes:
Locations:
city: Hirosaki
country: Japan
facility: Hirosaki University Hospital
state: Aomori
city: Funabashi
country: Japan
facility: Funabashi Municipal Medical Center
state: Chiba
city: Kitakyushu
country: Japan
facility: Kokura Memorial Hospital
state: Fukuota
city: Isesaki
country: Japan
facility: Mihara Memorial Hospital
state: Gunma
city: Sapporo
country: Japan
facility: Nakamura Memorial Hospital
state: Hokkaido
city: Amagasaki
country: Japan
facility: Japan Organization of Occupational Health and Safety Kansai Rosai Hospital
state: Hyogo
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Nishinomiya
country: Japan
facility: Hyogo College of Medicine College Hospital
state: Hyogo
city: Tsukuba
country: Japan
facility: University of Tsukuba Hospital
state: Ibaraki
city: Morioka
country: Japan
facility: Iwate Prefectural Central Hospital
state: Iwate
city: Odawara
country: Japan
facility: Seisho Hospital
state: Kanagawa
city: Yokohama
country: Japan
facility: Yokohama Municipal Citizen's Hospital
state: Kanagawa
city: Tsu
country: Japan
facility: Mie University Hospital
state: Mie
city: Suita
country: Japan
facility: National Cerebral and Cardiovascular Center
state: Osaka
city: Hidaka
country: Japan
facility: Saitama Medical University International Medical Center
state: Saitama
city: Ube
country: Japan
facility: Yamaguchi University Hospital
state: Yamaguchi
city: Hiroshima
country: Japan
facility: Hiroshima City Hiroshima Citizens Hospital
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital
city: Niigata
country: Japan
facility: Niigata City General Hospital
city: Wakayama
country: Japan
facility: Wakayama Medical University Hospital
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References:
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.