Predix Pharmaceuticals Initiates Phase III Clinical Trial of PRX-00023 in Generalized Anxiety Disorder; Provides Positive, Preliminary Findings from Phase II Study
8/15/2005 9:00:19 AM
LEXINGTON, Mass. & RAMAT GAN, Israel, Aug 15, 2005 (BUSINESS WIRE) -- Predix Pharmaceuticals, a drug discovery and development company, today announced the initiation of its first pivotal Phase III trial of PRX-00023, the company's novel 5-HT1A agonist, in patients with generalized anxiety disorder (GAD). The primary objective of the study is to evaluate the efficacy of PRX-00023 in GAD as measured by the change from baseline in the Hamilton Rating Scale for Anxiety (HAM-A).
"The initiation of this pivotal Phase III trial of PRX-00023 is an important milestone for Predix," said Michael G. Kauffman, M.D., Ph.D., president and CEO of Predix Pharmaceuticals. "This is the first of three internally discovered and developed drug candidates, currently in clinical trials, to enter Phase III."
Predix is currently in discussions with the Food and Drug Administration (FDA) regarding a Special Protocol Assessment (SPA) for this trial. The FDA has accepted the proposed study design and primary endpoint while making recommendations regarding secondary endpoint selection which we have adopted. At the FDA's request, Predix is developing a detailed statistical analysis plan for this study to complete the SPA.
This Phase III study follows the recent completion of a Phase II study of PRX-00023 in patients with GAD. The Phase II study was an open-label, multi-center outpatient trial in 20 patients with the diagnosis of moderate-to-severe GAD at study entry (HAM-A score of 20 or higher). The primary objective was to assess the safety and tolerability of PRX-00023 during short-term treatment of patients with GAD. Following a one-week, single-blinded placebo run-in period, PRX-00023 was administered to patients in doses of 40 mg once daily orally for four days, followed by 80 mg once daily orally for 10 days and then 120 mg once daily orally for 14 days. The most frequently reported adverse event was flu-like symptoms, occurring in three patients.
There were no serious adverse events or drug-related adverse events leading to discontinuation in the Phase II study. The only patient discontinuation was due to an adverse event that was not deemed drug-related. Although this trial was not designed to demonstrate statistical significance, preliminary results from the secondary efficacy objectives, available for 19 of the 20 patients, were encouraging. PRX-00023, given for four weeks, significantly lowered measures of anxiety from baseline in this trial, including the HAM-A total score, HAM-A psychic subscale score, CGI-Global Improvement score, and Hospital Anxiety and Depression scale. For example, analysis of HAM-A scores showed that 13 of 19 patients (68%) were "responders" with a reduction in their HAM-A score from baseline of at least 40%. Further, six of 19 patients (32%) experienced a "remission" of anxiety (i.e., a return to normal function), with a reduction in HAM-A score to seven or less during treatment with PRX-00023. These results are preliminary and are based on a small number of patients and are not necessarily predictive of results in later-stage clinical trials with larger and more diverse patient populations.
Stephen Donahue, M.D., vice president of clinical and regulatory affairs added, "Our goal in this program is to develop PRX-00023 as a once-daily drug to treat anxiety and depression with no sexual side effects and with a rapid onset of action. We are very pleased with the initial safety and efficacy data from our Phase I and II trials. Our Phase II study demonstrated that PRX-00023 was well-tolerated over four weeks, and none of the patients discontinued due to drug-related adverse events. Further, we observed significant improvement from baseline in key markers of anxiety over four weeks, and more than 30 percent of patients treated with PRX-00023 returned to normal function, free of anxiety symptoms."
Phase III Study Design
The Phase III trial is an eight-week, double-blind, placebo-controlled, multi-center study. The trial includes approximately 20 sites in the United States and is expected to enroll up to 310 patients with moderate-to-severe GAD who will be randomized into one of two arms, consisting of approximately 155 patients each: a placebo arm, or a PRX-00023 treatment arm, in which patients receive a dose of 40 mg administered over a three-day period followed by an 80 mg once daily for the remainder of the study. The primary objectives in this trial are to evaluate the efficacy of PRX-00023 in GAD as measured by the change from baseline in the HAM-A scale, and to assess the safety and tolerability of PRX-00023 during treatment of patients with GAD. The HAM-A scale is the only FDA accepted standard for the evaluation of anti-anxiety activity, and it is used in all pivotal trials of drug candidates for the treatment of GAD. This trial will be the first of at least two pivotal trials with PRX-00023 for the treatment of GAD.
PRX-00023 is Predix's lead drug candidate and represents a novel, highly selective , non-azapirone class of 5-HT1A agonists discovered using PREDICT(TM), the company's proprietary GPCR modeling, screening and lead optimization technology. Buspirone is currently the only 5-HT1A agonist approved in the United States for GAD, but must be taken three times a day, requires approximately three weeks of dose adjustment to reach therapeutic levels, and may cause lightheadedness and nausea. Several other 5-HT1A agonists have shown efficacy in Phase II and III clinical trials in depression. However, most of these drugs belong to a chemical class of drugs called azapirones and their development has been hindered by poor tolerability at therapeutic doses, rapid metabolism, resulting in a short half-life and, therefore, requiring multiple daily dosing, and the requirement of slow dose escalation to effective doses because of nausea and lightheadedness, which are thought to be caused by their binding to off-target G-Protein Coupled Receptors (GPCRs).
In contrast, PRX-00023 is designed to have minimal affinity for the GPCRs associated with the side effects of 5-HT1A agonists that are in the azapirone chemical class, and to have a more convenient dosing profile than azapirones.
Predix Pharmaceuticals Holdings, Inc. is a pharmaceutical company focused on the discovery and development of novel, highly selective, small-molecule drugs that target GPCRs and ion channels. Using its proprietary drug discovery technology and approach, Predix has advanced three drug candidates into clinical trials and has six additional programs in preclinical development and discovery. Predix's lead clinical-stage drug candidate, PRX-00023, completed a Phase II clinical trial in patients with GAD in July 2005 and entered the first of at least two pivotal Phase III clinical trials for this indication in August 2005. Its two other clinical-stage drug candidates, PRX-03140 for the treatment of Alzheimer's disease and PRX-08066 for the treatment of Pulmonary Arterial Hypertension are in Phase I clinical trials. For more information on Predix, please visit www.predixpharm.com.