Clinical trial NCT00756249: Safety Study of Carbamylated Erythropoietin (CEPO) to Treat Patients With Acute Ischemic Stroke
Official title: Randomised, Double-blind, Placebo-controlled, Single-dose, Dose-escalation Study of the Safety, Tolerability, and Pharmacokinetics of Lu AA24493 in Acute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Ischemic Stroke
Keywords: Acute ischemic stroke
Erythropoietin
Carbamylated
Neuroprotection
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2008-09-22
Enrollment: 16
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of the study is to determine whether carbamylated erythropoietin (CEPO) is a safe treatment for patients who have suffered an acute ischemic stroke.

Detailed description: Acute ischemic stroke is a major cause of death and severe disability. There is only one approved pharmacological treatment, Alteplase, which has to be administered within 3 hours from symptom onset. Consequently, only about 2-3% of patients world wide with ischemic strokes are treated. The naturally occurring hormone, erythropoietin (EPO), is able to protect various neuronal tissues from ischemic injury and is beneficial in animal models of acute ischemic stroke. However, treatment of stroke with EPO is undesirable due to its ability to stimulate production of red blood cells and to promote the blood to coagulate. Lu AA24493 is a modified (carbamylated) version of EPO, neuroprotective but without the haematopoietic side effects. Lu AA24493 is developed for treatment of patients with acute ischemic stroke.

In this safety study of single doses with Lu AA24493, patients will receive Lu AA24493 within 12-48 hours from symptom onset.

Eligibility criteria: Inclusion Criteria:

* Age between 50 and 90 years
* Clinical diagnosis of acute ischemic stroke
* Measurable stroke-related deficit
* Patient is stable
* Treatment can be initiated between 12 hours and 48 hours after the onset of stroke
* Expected hospital stay of at least 72 hours after study medication
* If female then not of childbearing potential

Exclusion Criteria:

* Primary intracerebral haemorrhage (ICH), or parenchymal haemorrhagic transformation of infarction (type PHI or PHII as defined in ECASS), subarachnoid haemorrhage (SAH), arterio-venous malformation (AVM), cerebral aneurysm, or cerebral neoplasm
* Treated with a thrombolytic \<24 hours (if \>24 hours excluded ICH then eligible)
* Score \>0 on the NIHSS item 1a
* Pre-stroke mRS score \>1
* Uncontrolled hypertension
* Previous treatment with erythropoietin
* Clinically significant abnormal ECG
* Cerebral pathology
* Received or donated blood within previous 3 months

Primary outcomes:
measure: National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS)
timeFrame: Baseline, Day 7, Day 30; for NIHSS also Day 2 and 3
Secondary outcomes:
measure: Pharmacokinetics, immunogenicity and mechanistic biomarkers (S-100b, glial fibrillary acidic protein (GFAP), matrix metalloproteinase 9 (MMP-9))
timeFrame: Baseline, Day 1-4, Day 7 and Day 30
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: FI004
city: Paris
country: France
facility: FR002
city: Breda
country: Netherlands
facility: NL005
city: Singapore
country: Singapore
facility: SG003
city: Glasgow
country: United Kingdom
facility: GB001
Study officials:
affiliation: LundbeckClinicalTrials@lundbeck.com
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References: