Envivo Pharmaceuticals Announces Initiation of Clinical Safety and Biomarker Study of Alpha-7 Nicotinic Agonist, EVP-6124, in patients with Schizophrenia
April 02, 2008
EnVivo Pharmaceuticals announced today that it has initiated a clinical safety and biomarker study of its alpha-7 nicotinic agonist (EVP-6124) in Schizophrenia patients chronically treated with atypical antipsychotic medications. The objectives of this study are to evaluate the safety of multiple doses of EVP-6124 in this patient population, to investigate potential drug-drug interactions, and to determine the effects of EVP-6124 on sensitive electrophysiology markers (the P50 auditory evoked response and mismatch negativity) in Schizophrenia patients.
The principle investigator is Dr. Sheldon H. Preskorn and the study is being conducted at the Clinical Research Institute (CRI) in Wichita Kansas. Dr. Preskorn is Chief Executive Officer and Medical Director of the CRI which specializes in early clinical pharmacology studies in patients with psychiatric and neurologic diseases. Dr. Preskorn is also a Professor in the Department of Psychiatry and Behavioral Sciences at the Kansas University of School of Medicine – Wichita.
This trial is enrolling approximately 20 Schizophrenia patients treated with a stable dose of an atypical antipsychotic drug. Patients are receiving one of two doses of EVP-6124 or a placebo for up to 28 days. Previous Phase 1 studies have characterized the safety and cognitive effects of single and multiple EVP-6124 doses as low as 0.1 mg/day. Based on these studies, two doses of EVP-6124 within the expected efficacy range are being examined in this ongoing study. The results of this safety and biomarker trial will be used to design larger Phase 2 studies of EVP-6124 in patients with Schizophrenia. These trials will be initiated later in 2008 or in early 2009.
“Our extensive Phase I work has paid off”, remarked Kees Been, President and CEO of EnVivo. “We already have results that suggest that EVP-6124 is associated with cognitive benefits in learning and memory and we believe we understand the dosing range in which to expect efficacy. This significantly enhances the probability of success of the upcoming biomarker and Phase II studies.”
About Electrophysiological Biomarkers in Schizophrenia Patients
Patients with Schizophrenia invariably have abnormalities in sensory gating thought to be responsive to alpha-7 nicotinic receptor stimulation. When repetitive auditory stimuli are presented to a patient with Schizophrenia, the evoked electrophysiologic brain response (the P50 response measured 50 msec after each stimulus) in such patients is abnormal. Normal individuals suppress this response by up to 80% while patients with Schizophrenia have decreased ability to suppress the response to a second stimulus. Sensory gating abnormalities in Schizophrenia have been linked to an allele on chromosome 15, the gene locus for the alpha-7 receptor. Alpha-7 nicotinic agonists have been recently shown to improve cognition and the P50 response in patients with Schizophrenia. Thus, the P50 response may be a sensitive biomarker for assessing the pro-cognitive effect of an alpha-7 nicotinic agonist in Schizophrenia.
Mismatch negativity is another electrophysiological biomarker that has been shown to be abnormal in patients with Schizophrenia. Mismatch negativity is assessed by the ability of the patient to detect a unique stimulus imbedded in a repetitive train of otherwise identical auditory stimuli. Assessments of the effects of EVP-6124 on the P50 evoked response and mismatch negativity may be very useful in determining the threshold and optimal dose of EVP-6124 for further development.
EVP-6124 is a potent full agonist of the alpha-7 nicotinic receptor. This drug candidate has been shown to have excellent CNS penetration, oral bioavailability, pharmacokinetics, and metabolic profile. In multiple preclinical animal models of cognition, EVP-6124 has had significant beneficial effects.