Clinical trial NCT01104467: Clinical Study of Desmoteplase in Japanese Patients With Acute Ischemic Stroke
Official title: Randomised, Double-blind, Placebo-controlled, Dose-escalation Study of Desmoteplase in Japanese Patients With Acute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Ischemic Stroke
Keywords: Acute Ischemic Stroke
Desmoteplase
Japan
Safety
Stroke
Tolerability
Lead sponsor: Lundbeck Japan K. K.
Sponsor class: INDUSTRY
First posted: 2010-04-15
Enrollment: 48
Sex: ALL
Minimum age (years): 20
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate whether desmoteplase is safe and tolerated when given to Japanese patients with acute ischemic stroke

Detailed description: The study is a safety and tolerability study of desmoteplase in Japanese patients with acute ischemic stroke. The study will test two doses

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of acute ischemic stroke
* Provided Informed Consent
* Male or female
* Aged between 20 and 85 years inclusive
* Treatment within 3-9 hr after onset of stroke symptoms.
* NIHSS score of 4-24 inclusive with clinical signs of hemispheric infarction
* Must receive IMP within 60 minutes after brain imaging
* Cerebral artery occlusion or high-grade stenosis in MCA

Exclusion Criteria:

* Pre-stroke mRS score of \>1
* Previously exposed to desmoteplase
* Scores \>2 on NIHSS question 1a indicating coma
* History or clinical presentation of ICH, subarachnoid haemorrhage (SAH), arterio-venous malformation (AVM), moyamoya disease, cerebral neoplasm or aneurysm
* Current use of oral anticoagulants and a prolonged prothrombin time (INR \>1.6)
* Treated with heparin in the previous 48 hours and has a prolonged partial thromboplastin time
* Baseline platelet count \<100,000/mm3
* Baseline haematocrit of \<0.25
* Baseline blood glucose \<50 mg/dl or \>200 mg/dl
* Uncontrolled hypertension defined by a blood pressure, systolic \>185 mmHg or diastolic \>110 mmHg on at least 2 separate occasions at least 10 minutes apart
* Patient has hereditary or acquired hemorrhagic diathesis
* Gastrointestinal or urinary bleeding within the past 21 days
* Arterial puncture in a non-compressible site within the previous 7 days
* Another stroke or a serious head injury in the past 6 weeks
* Major surgery or serious injury, including other sites than the head, within the preceding 14 days
* Seizure at the onset of stroke
* Acute myocardial infarction (AMI) within the previous 3 weeks
* Thrombolytic within the previous 72 hr
* Pregnant

Other inclusion and exclusion criteria may apply.

Primary outcomes:
measure: To evaluate the safety and tolerability of desmoteplase doses of 70 µg/kg and 90 µg/kg in Japanese patients with acute ischemic stroke as measured by the presence of symptomatic intracranial haemorrhage (sICH) within 72 hours after IMP
timeFrame: 90 days
Secondary outcomes:
measure: To evaluate the clinical improvement at Day 90 after administration of Investigational Medicinal Product (IMP) as measured by modified Rankin Scale (mRS)
timeFrame: 90 days
measure: To evaluate the clinical improvement at Day 7 and 30 after administration of IMP as measured by modified Rankin Scale (mRS)
timeFrame: Day 7 and Day 30
measure: To evaluate recanalisation at 18±6 hr after administration of IMP
timeFrame: 18±6 hr after administration of IMP
measure: To evaluate change in infarct size at 18±6 hr relative to pre-treatment infarct size
timeFrame: 18±6 hr after administration
measure: To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of desmoteplase
timeFrame: 0.5 - 9 hr
measure: To evaluate the immunogenicity of desmoteplase
timeFrame: Day 7, Day 30, Day 90
measure: To explore the predictive value of different volumes of absolute mismatch for the clinical response and other objectives
timeFrame: Day 90
Other outcomes:
Locations:
city: Akita
country: Japan
facility: JP006
city: Fukuoka
country: Japan
facility: JP021
city: Hiroshima
country: Japan
facility: JP018
city: Isesaki
country: Japan
facility: JP007
city: Kagoshima
country: Japan
facility: JP024
city: Kawasaki
country: Japan
facility: JP011
city: Kobe
country: Japan
facility: JP015
city: Kumamoto
country: Japan
facility: JP022
city: Nagoya
country: Japan
facility: JP012
city: Nishinomiya
country: Japan
facility: JP026
city: Okayama
country: Japan
facility: JPO17
city: Sapporo,Hokkaido
country: Japan
facility: JP002
city: Sapporo
country: Japan
facility: JP001
city: Sendai
country: Japan
facility: JP004
city: Shibata
country: Japan
facility: JP005
city: Suita
country: Japan
facility: JP014
city: Tokushima
country: Japan
facility: JP020
city: Tokyo
country: Japan
facility: JP009
city: Toyota
country: Japan
facility: JP013
Study officials:
affiliation: LundbeckClinicalTrials@lundbeck.com
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References:
citation: Mori E, Minematsu K, Nakagawara J, Hasegawa Y, Nagahiro S, Okada Y, Truelsen T, Lindsten A, Ogawa A, Yamaguchi T; DIAS-J Investigators. Safety and Tolerability of Desmoteplase Within 3 to 9 Hours After Symptoms Onset in Japanese Patients With Ischemic Stroke. Stroke. 2015 Sep;46(9):2549-54. doi: 10.1161/STROKEAHA.115.009917. Epub 2015 Aug 6.