Cognitive impairment is a cause of significant disability in patients with schizophrenia. To date, no drug has been approved for this indication by the U.S. Food and Drug Administration. This article presents findings suggesting that a medication targeting the alpha-7 nicotinic acetylcholine receptor (α7 nAChR) might meet this need. This single-center, randomized, parallel-group, double-blind,placebo-controlled study examined 21 medically stable patients with schizophrenia or schizoaffective disorder treated with second generation antipsychotics. Patients were treated with a daily dose of either 0.3 mg (n=8) or 1.0 mg (n=9) of EVP-6124, an α7 nAChR partial agonist, or placebo (n=4). Treatment continued for 21 days while patients continued their usual antipsychotic medication: aripiprazole (10–30 mg/day), olanzapine (10–20 mg/day), paliperidone (3–12 mg/day), or risperidone (2–16 mg/day). Cognitive test performance, eventrelated electroencephalographic (EEG) potentials, clinical symptoms, laboratory values, and clinical side effects were measured. EVP-6124 was well tolerated and showed positive, and in some cases, dose-dependent effects on several EEG responses, especially the Mismatch Negativity and P300 potentials. Positive effects were also found in performance on cognitive tests that measured non-verbal learning, memory, and executive function. This study is an example of the type of early proof of concept trial that is done to enable drug developers to evaluate whether to continue research on an agent. Based on the promising findings in this study, larger phase II studies were initiated to further test the pro-cognitive effects of EVP-6124 in patients with chronic schizophrenia.
Clinical Trials Registration: Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients with Schizophrenia, NCT01556763 http://clinicaltrials.gov/ct2/show/NCT01556763?term=NCT01556763&rank=1 (Journal of Psychiatric Practice 2014;20:12–24)
PRESKORN: University of Kansas School of Medicine-Wichita and Kansas University-Wichita Clinical Trials Unit; GAWRYL, DGETLUCK, and HILT: EnVivo Pharmaceuticals, Inc., Watertown, MA; PALFREYMAN: ChemDiv, Inc., San Diego, CA; BAUER: University of Connecticut School of Medicine, Farmington.
Over his career, Dr. Preskorn has worked with over 100 pharmaceutical companies in the United States and throughout the world. Over the past year, Dr. Preskorn has received grants/research support from or has served as a consultant, on the advisory board, or on the speakers bureau for the following: Abbott, Assurex Health, AstraZeneca, Eisai, Envivo, Impax Laboratories, Johnson & Johnson, Merck, National Institute of Mental Health, Naurex, Pfizer, Stanley Medical Research Institute, Sunovion, and Taisho. D. Hilt, M. Gawryl, N. Dgetluck, and M. Palfreyman were full time employees of Envivo during the conduct of the study. M Palfreyman is currently a full-time employee of ChemDiv and a member of the Psychiatry Scientific Advisory Board (SAB) of EnVivo Pharmaceuticals. Dr Bauer served as a consultant for Envivo for this study.
The authors acknowledge the contributions of Diane Hilger, LPN, CCRC, who was the principal coordinator on the study, Bryan Baker, RN, MSM, CCRC, who was the overall clinical operations manager, and the entire staff of the Clinical Research Institute, now the Kansas University-Wichita Clinical Trials Unit. They also acknowledge Ruth Ross for editorial assistance in preparing the manuscript.
EnVivo Pharmaceuticals provided financial support and experimental drug/placebo capsules for this clinical study and financial support for editorial assistance in preparing the manuscript. A preliminary version of these data was presented at the ACNP Meeting in December, 2009.
Please send correspondence to: Sheldon H. Preskorn, MD, Kansas University-Wichita Clinical Trials Unit,1010 N. Kansas, Wichita KS 67214, firstname.lastname@example.org