Amkor Pharmaceuticals, Inc. today reports that all clinical
activities of its Phase I, double-blinded, randomized
placebo-controlled ascending intravenous (IV) single dose (both
loading and maintenance infusion) study assessing the safety
tolerance, and pharmacokinetics (PK) of Neu2000KL in 95 healthy young
and elderly volunteers has been completed.
Neu2000KL is a moderate N-methyl d-aspartate (NMDA) receptor
antagonist and potent antioxidant which is designed as a dual-acting
neuroprotectant for concurrent blockade of both NMDA receptor-mediated
excitotoxicity and oxidative stress, two major pathways of neuronal
cell death occurring in stroke and trauma. The drug has shown
remarkable protection with extended therapeutic time windows in
various animal models of transient and permanent ischemic brain
injury. The therapeutic potential of Neu2000KL has also been verified
in animals subjected to spinal cord injury and sudden cardiac arrest.
Based upon these proof of principle efficacy and safety studies in
various animal models, the phase I study of Neu2000KL was conducted in
the USA under an investigational new drug application (IND) in
collaboration with one of the largest contract research organization
(CRO) in the world.
The phase I study was performed as a three-part study to assess
the safety of Neu2000KL at target doses in 64 volunteers (in eight
cohorts, each with 6 subjects on Neu2000 and 2 on placebo), at
maximally deliverable doses in 16 young volunteers (in two cohorts)
and at target doses in 15 elderly volunteers over the age of 65 (in
two cohorts). The results demonstrated that Neu2000KL can be safely
administered and is well-tolerated at doses of up to 6,000 mg, more
than sufficient to support advancement into phase II studies for both
ischemic stroke and sudden cardiac arrest at clinically relevant
doses.
Interim safety evaluations of Cohorts 1 to 12 identified no
critical safety issues. In fact, no serious adverse event (AE)
occurred, and no dose-dependent AEs could be identified. Psychiatric
symptoms, a major side effect often caused by NMDA antagonists in
humans, were not observed in young or elderly human volunteers treated
with Neu2000KL. According to the new Food and Drug Administration
(FDA) guidance requiring a non-clinical safety profile of NMDA
antagonists before initiation of phase II study, the safety of
Neu2000KL has also been extensively investigated and its safety
verified in rats treated with an extremely high dose of 200 mg/kg via
I.V. route by a specialized CRO in the US.
Based on the robust data arising from this phase I study, and a
supporting regulatory package of toxicology studies, a phase II study
will be initiated in 2008 under a European clinical trial application
and the current US IND. Stroke patients will be enrolled by leading
investigators from more than six countries by one of the world´s top
three CROs which has internationally recognized, leading-edge, medical
imaging competence and expertise.
Dr. Byoung J. Gwag, a professor at Ajou University School of
Medicine and the Chairman of the Board of Directors of Neurotech in
South Korea, said today, that he was impressed by the evident
satisfactory human safety profile of Neu2000KL at beyond maximally
effective doses in animal models of stroke. He was confident that the
carefully-conceived, design-engineered Neu2000KL would show promise in
stroke treatment, and fulfill an unmet medical need. He is reassured
by hiring the best clinical consultants to design phase I, and now
phase II studies, to measure the potential effect and benefit of
Neu2000KL in man using a unique, competitive clinical phase II design
strategy.
The planned 2008/2009, largely European multinational, multicentre
phase IIa proof-of-concept efficacy trial of Neu2000KL in the stroke
patient population, will provide greater than 80% power to detect a
40% decrease in stroke volume growth compared to placebo. Eligible
patients will be randomized (1:1) to be administered study drug or
placebo within 6 hours of stroke symptoms. This phase II study has
sophisticated and novel design aspects. A population with documented
magnetic resonance imaging (MRI) evidence of ischemia by magnetic
resonance angiography (MRA) will be enrolled. Endpoints will include
infarct growth measured by echo-planar imaging capability for
performance of MRI; gradient recalled echo (GRE), diffusion-weighted
imaging (DWI) / apparent diffusion coefficient (ADC)
perfusion-weighted imaging (PWI), fluid-attenuated inversion-recovery
(FLAIR), and intracranial MRA. A National Institutes of Health (NIH)
Stroke Scale score endpoint, modified with expanded deficit-specific
subscales, will be developed and validated to better reflect clinical
outcomes and accommodate clinical stroke heterogeneity.
Amkor Pharma, Inc is an American subsidiary company of Neurotech
Pharmaceuticals, Co., Ltd. whose mission is to carry out world-wide
clinical studies of therapeutic drugs for treating stroke, trauma, and
neurodegenerative diseases.
Neurotech Pharmaceuticals Co., Ltd. was founded by eight Korean
professors with specialties in neuropharmacology, neurology, medicinal
chemistry, ophthalmology, and genetics who were educated, trained, and
held faculty appointments at top medical universities in the US such
as Washington University, Harvard University, and the University of
Pennsylvania. Neurotech has four drug pipelines targeting stroke
Alzheimer´s disease, inflammatory diseases, and neuropathy in parallel
with technology platforms such as commercialized biological cell
lines. Drug development at Neurotech is steered by a wide network of
collaborating CROs and drug development consulting firms, and two
scientific advisory committees consisting of American and Korean
academics and ex-international industry executives.
These clinical developments reported by Amkor, the American
subsidiary of Neurotech, constitute encouraging news to neurological
and cardiovascular interest groups.
