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 improvements in symptoms compared to placebo-treated patients observed as early as day five of treatment and at each subsequent time point studied. The results of this study were consistent with the results observed in the two previously completed pivotal placebo-controlled cariprazine studies in this patient population. Further analyses of the data will be completed in the coming weeks. Cariprazine is also currently being investigated in clinical studies for patients with schizophrenia, bipolar depression, and as an adjunct treatment for Major Depressive Disorder.
“As we continue to move forward with the development of this important compound, these positive phase III results further demonstrate the opportunity for cariprazine as a potential new treatment option for patients suffering from bipolar mania” said Marco Taglietti, MD, Senior Vice President of Research and Development and President, Forest Research Institute.
“In the three consecutive positive trials, statistically significant results demonstrated improvement in symptoms compared to placebo, importantly including the low dose range arm. We consider today’s results a major milestone achieved on the long road towards bringing such a promising product to the market,” commented Zsolt Szombathelyi, MD, 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, 497 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 into three treatment groups and received at least one dose of either cariprazine 3-6mg/day (n=167), cariprazine 6-12 mg/day (n=169) or placebo (n=161). Following a wash-out screening period of four to seven days, patients received treatment for up to three weeks, which 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) analyses. The YMRS is a comprehensive, clinician-rated instrument used to assess the severity of mania in bipolar patients, including such parameters as elevated mood, increased motor activity-energy, sleep, and irritability. Statistically significant improvement was noted in both cariprazine dose groups (3-6mg/day: -6.1 points, p <0.001 and 6-12 mg/day: -5.9 points, p < 0.001) relative to patients receiving placebo on the YMRS scale by MMRM analysis.
Overall premature discontinuation rates (all causes, including adverse-event related) were 23% for cariprazine 3-6 mg/day, 30% cariprazine 6-12 mg/day, and 24% for placebo. The most common adverse events (greater than or equal to 10% and twice the rate of placebo) observed in the study were akathisia (both cariprazine groups) and constipation (cariprazine 6-12 mg/day). Cariprazine was generally well tolerated with discontinuations due to adverse events observed in 9% of patients for the cariprazine 3-6 mg/day, 15% for the cariprazine 6-12 mg/day, and 5% for the placebo group.
Cariprazine, discovered by researchers at Gedeon Richter, is an orally active, potent dopamine D3-preferring D3/D2 receptor partial agonist. 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 for MDD.
About Gedeon Richter Plc.
Gedeon Richter Plc. (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 in the field of gynaecology. Richter’s consolidated sales were approximately EUR 1.1 billion (USD 1.5 billion) while its market capitalization amounted to EUR 2.1 billion (USD 2.7 billion) in 2011. The product portfolio of the Company covers almost all important therapeutic areas, including gynaecology, central nervous system and cardiovascular. The Company has the largest R&D unit in Central Eastern Europe. Original research activity focuses on CNS disorders with main clinical targets being schizophrenia, anxiety, chronic pain and depression. With its widely acknowledged steroid chemistry expertise Richter 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
Vice President - Investor Relations