Robert E Litman1, Mark A Smith2, James J Doherty3, Alan Cross4, Shane Raines5, Lev Gertsik6, Stephen R Zukin7. 1. CBH Health, LLC, 9210 Corporate Blvd., Suite 110, Rockville, MD, United States; Georgetown University, 3700 O St. NW, Washington, DC 20057, United States. 2. AstraZeneca Pharmaceuticals, 1800 Concord Pike, Wilmington, DE 19542, United States; Teva Pharmaceuticals, 41 Moores Rd., Frazer, PA 19355, United States. 3. AstraZeneca Pharmaceuticals, 1800 Concord Pike, Wilmington, DE 19542, United States; Sage Therapeutics, 215 First St., Cambridge, MA 02142, United States. 4. AstraZeneca Pharmaceuticals, 1800 Concord Pike, Wilmington, DE 19542, United States. 5. AstraZeneca Pharmaceuticals, 1800 Concord Pike, Wilmington, DE 19542, United States; 2b Analytics, LLC, 128 Westminster Dr., Wallingford, PA 19086, United States. 6. California Clinical Trials Medical Group, 1560 East Chevy Chase Dr., Suite 140, Glendale, CA 91206, United States. 7. AstraZeneca Pharmaceuticals, 1800 Concord Pike, Wilmington, DE 19542, United States; Forest Research Institute, Jersey City, NJ, United States; Haborside Financial Center, Plaza V, Jersey City, NJ 07311, United States.
Abstract
INTRODUCTION: Activation of metabotropic glutamate (mGluR2/3) receptors has been proposed as an alternative mechanism to dopaminergic-based antipsychotics to correct glutamatergic deficits hypothesized to underlie schizophrenia symptoms. This study investigates the efficacy and safety of AZD8529, a selective positive allosteric modulator (PAM) at the mGlu2 receptor, in symptomatic patients with schizophrenia. METHODS: Patients were randomized to receive AZD8529 40 mg, risperidone 4 mg, or placebo as monotherapy. Treatment lasted for 28 days, and clinical efficacy was assessed using Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI) scores. RESULTS: There were no significant differences between patients treated with AZD8529 versus placebo in change from baseline to endpoint in PANSS total, negative and positive symptom subscale, or CGI-S scores. In contrast, risperidone demonstrated significant efficacy relative to placebo. CONCLUSION: These results do not support a role for the mGluR-2 PAM AZD8529 as an antipsychotic and indicate that positive modulation of mGluR type 2 receptors alone is not sufficient for antipsychotic effects in acutely ill schizophrenia patients.
RCT Entities:
INTRODUCTION: Activation of metabotropic glutamate (mGluR2/3) receptors has been proposed as an alternative mechanism to dopaminergic-based antipsychotics to correct glutamatergic deficits hypothesized to underlie schizophrenia symptoms. This study investigates the efficacy and safety of AZD8529, a selective positive allosteric modulator (PAM) at the mGlu2 receptor, in symptomatic patients with schizophrenia. METHODS:Patients were randomized to receive AZD8529 40 mg, risperidone 4 mg, or placebo as monotherapy. Treatment lasted for 28 days, and clinical efficacy was assessed using Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI) scores. RESULTS: There were no significant differences between patients treated with AZD8529 versus placebo in change from baseline to endpoint in PANSS total, negative and positive symptom subscale, or CGI-S scores. In contrast, risperidone demonstrated significant efficacy relative to placebo. CONCLUSION: These results do not support a role for the mGluR-2 PAM AZD8529 as an antipsychotic and indicate that positive modulation of mGluR type 2 receptors alone is not sufficient for antipsychotic effects in acutely ill schizophreniapatients.
Authors: Ranganath D Rattehalli; Sai Zhao; Bao Guo Li; Mahesh B Jayaram; Jun Xia; Stephanie Sampson Journal: Cochrane Database Syst Rev Date: 2016-12-15
Authors: Omar K Sial; Eric M Parise; Lyonna F Parise; Tamara Gnecco; Carlos A Bolaños-Guzmán Journal: Behav Brain Res Date: 2020-02-01 Impact factor: 3.332