Seattle, United States
Amkor Pharmaceuticals, Inc. 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.
Source: Business Wire (Business Wire India)