NEW YORK & BUDAPEST, Hungary--(BUSINESS WIRE)-- Forest Laboratories, Inc. (NYSE:FRX - News) and Gedeon Richter Plc today announced preliminary top-line results from a Phase III clinical trial of cariprazine (RGH-188), an investigational antipsychotic agent, in patients with acute mania associated with bipolar I disorder. For the primary endpoint, the Young Mania Rating Scale (YMRS), the data showed that cariprazine-treated patients with acute manic episodes experienced significant symptom improvement compared to placebo-treated patients seen as early as day four of treatment and at each subsequent time point studied. Further analyses of the data will be completed in the coming weeks. Cariprazine is also being investigated in clinical studies for patients with schizophrenia, bipolar depression, and as an adjunct treatment in MDD.
“These exciting positive Phase III results in patients with bipolar mania demonstrate the potential of cariprazine as a novel antipsychotic agent,” said Marco Taglietti, MD., Senior Vice President of Research and Development and President, Forest Research Institute. “We will continue to investigate the therapeutic benefits of this novel dual acting D3/D2 compound across other CNS disorders as well.”
"We are encouraged by the positive top-line results shown in this Phase III study. These data together with those of the Phase II program prove that cariprazine provides a clinically meaningful improvement with good tolerability in patients with acute mania associated with bipolar I disorder. It also confirms, the D3/D2 partial agonist research concept elaborated by Richter’s researchers was a valuable and novel approach,” commented Zsolt Szombathelyi, M.D., Research Director of Gedeon Richter Plc.
About the Study
This Phase III, multicenter, double-blind, placebo- controlled, parallel-group study evaluated the efficacy, safety, and tolerability of cariprazine monotherapy in patients with acute mania associated with bipolar I disorder. During the five-week study, 312 men and women, 18-65 years of age meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for bipolar I disorder were randomized and received at least one dose of either cariprazine, 3-12mg/day (N=158), or placebo (N=154). Following wash-out screening period of four to seven days, patients were given 1-4 capsules (cariprazine or placebo) daily. The treatment period lasted three weeks and was followed by a two week period of safety assessments. Patients were hospitalized throughout screening and for at least the first 14 days following initiation of treatment.
The primary, protocol-specified, endpoint was change from baseline to Week 3 on the YMRS, using the mixed effects model of repeated measures (MMRM) analysis. The YMRS is a comprehensive, clinician-rated instrument used to assess the severity of mania in bipolar patients, and includes such parameters as elevated mood, increased motor activity energy, sleep, and irritability. Statistically significant improvement was noted in patients receiving cariprazine (3-12mg/day) relative to patients receiving placebo on the YMRS scale (-19.6 cariprazine vs. -15.3 placebo, p<0.001) by MMRM analysis.
Overall premature discontinuation rates (all causes, including adverse event related) were 32% for patients receiving cariprazine and 31% for patients receiving placebo. The most common adverse events (=10% and twice the rate of placebo) observed in the study were akathisia, extrapyramidal disorder, tremor, dyspepsia, and vomiting. Cariprazine was generally well tolerated with discontinuations due to adverse events observed in 10% of the cariprazine group and 7% of the placebo group.
Cariprazine, discovered by researchers at Gedeon Richter, is an orally active, potent dopamine D3-preferring D3/D2 receptor partial agonist. In addition, cariprazine has a low potency at other receptor sites, such as 5-HT2C, histamine H1, muscarinic, and adrenergic receptor sites, which have been associated with adverse events. Cariprazine is also under development for the treatment of schizophrenia, bipolar depression, and as an adjunct treatment in MDD.
About Gedeon Richter Plc.
Gedeon Richter Plc., (http://www.richter.hu) headquartered in Budapest/Hungary, is a major pharmaceutical company in Hungary and one of the largest in Central Eastern Europe, with an expanding direct presence in Western Europe. Richter’s consolidated sales was approximately EUR 1 billion (USD 1.3 billion) while its market capitalization amounted to EUR 2.9 billion (USD 3.8 billion) in 2010. The product portfolio of the Company covers almost all important therapeutic areas, including cardiovascular, central nervous system and gynecology. The Company has the largest R&D unit in Central Eastern Europe. Original research activity focuses exclusively on CNS disorders with main clinical targets being schizophrenia, anxiety, chronic pain and depression. With its widely acknowledged steroid chemistry expertise the Company is also a significant player in the female healthcare field worldwide.
About Forest Laboratories
Forest Laboratories’ (NYSE:FRX - News) longstanding global partnerships and track record developing and marketing pharmaceutical products in the United States have yielded its well-established central nervous system and cardiovascular franchises and innovations in anti-infective and respiratory medicine. The Company’s pipeline, the most robust in its history, includes product candidates in all stages of development across a wide range of therapeutic areas. The Company is headquartered in New York, NY. To learn more, visit www.FRX.com.
Except for the historical information contained herein, this release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements involve a number of risks and uncertainties, including the difficulty of predicting FDA approvals, the acceptance and demand for new pharmaceutical products, the impact of competitive products and pricing, the timely development and launch of new products, and the risk factors listed from time to time in Forest Laboratories’ Annual Report on Form 10-K, Quarterly Report on Form 10-Q, and any subsequent SEC filings.
Forest Laboratories, Inc.Frank J. Murdolo, 1-212-224-6714Vice President - Investor RelationsFrank.Murdolo@frx.com