Major Depressive Disorder
Wyeth Pharmaceuticals announces that data from two Phase 3 clinical studies of PRISTIQ (desvenlafaxine), an investigational serotonin-norepinephrine reuptake inhibitor (SNRI), showed that adult patients who received a 50 mg/day dose of PRISTIQ for the treatment of major depressive disorder (MDD) experienced a statistically significant reduction in the symptoms of major depression compared to placebo. The two studies, which evaluated efficacy and safety of PRISTIQ for the treatment of MDD at fixed doses of 50 mg/day and 100 mg/day, will be presented today at a major medical meeting. This will be the first time an analysis of the 50 mg/day dose for PRISTIQ for the treatment of MDD is presented.
In both studies, discontinuation rates due to adverse events (AEs) for PRISTIQ 50 mg/day were similar to placebo. In the two studies, the rates of discontinuation due to AEs for placebo and PRISTIQ 100 mg/day were three percent and seven percent, respectively.
"These findings show that PRISTIQ has the potential to reduce symptoms of MDD at doses as low as 50 mg once daily," says Philip Ninan, M.D., Vice President, Neuroscience, Global Medical Affairs. "The response rates of patients in the 50 mg/day dose groups are similar to the rates seen at higher doses. We are also encouraged by the tolerability profile shown in the two studies presented at this meeting. Notably, subjects in the 50 mg/day dose groups were not titrated from a lower dose when initiating therapy."
Wyeth submitted in August 2007 the results of the two studies to the U.S. Food and Drug Administration (FDA) as part of its complete response to the FDA approvable letter it received in January 2007 for PRISTIQ for the treatment of MDD. FDA action on the application is expected during the first quarter of 2008. The clinical data for PRISTIQ presented at the meeting represent only a portion of the data from the ongoing clinical development of PRISTIQ and are not necessarily representative of the totality of data and other information that may affect further development, regulatory review and/or commercialization of PRISTIQ.
More About the Studies
Poster 145: Liebowitz M., et al. Evaluation of the Efficacy and Safety of Fixed Doses of Desvenlafaxine Succinate at 50 mg and 100 mg in Outpatients with Major Depressive Disorder in 2 Placebo-Controlled Trials
Data presented are from two identically designed multicenter, randomized, double-blind, placebo-controlled, eight-week studies, one conducted outside of the United States involving 483 adult patients, and one in the U.S. with 447 adult patients. Primary efficacy in both trials was determined based on change from baseline score on the 17-item Hamilton Depression Rating Scale (HAM-D17). Patients in both desvenlafaxine groups started treatment at 50 mg/day. For the 100 mg/day group, the dose was increased to 100 mg/day on the eighth day of the study.
The results of both trials showed that at the 50 mg/day dose, desvenlafaxine was associated with a significant reduction in the symptoms of MDD as measured by HAM-D17 scores over eight weeks compared with placebo (ex-US: p=0.002, 50 mg = -13.2, placebo = -10.7; U.S.: p=0.018, 50 mg = -11.5, placebo = -9.5). While the 100 mg/day dose showed a statistically significant improvement in the international study versus placebo (p<0.001, 100 mg = -13.7), this dose did not statistically separate from placebo in the U.S. study (p=0.065, 100 mg = -11.0).
In the U.S. study, rates of discontinuation due to AEs for the placebo, desvenlafaxine 50 mg/day and desvenlafaxine 100 mg/day groups were 3 percent, 3 percent and 7 percent, respectively. In the international study, these rates for the placebo, desvenlafaxine 50 mg/day and desvenlafaxine 100 mg/day groups were 3 percent, 5 percent and 7 percent, respectively.
Adverse events in both of these studies that were reported by at least five percent of the subjects and twice the rate of placebo included asthenia, anorexia, anxiety, dizziness and insomnia. Events also reported by at least five percent of the subjects and twice the rate of placebo in the international study were nausea, somnolence and abnormal ejaculation; and in the U.S. study they were constipation, dry mouth, myalgia, impotence and sweating. In the U.S. study, nausea was not among the adverse events reported by at least five percent of the subjects and twice the rate of placebo.