Home About us Contact
|
Home About us Contact | ||
|
|
||
New Drug Application (new + drug_application)
Selected AbstractsSafety and tolerability of duloxetine in the treatment of major depressive disorder: analysis of pooled data from eight placebo-controlled clinical trialsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 5 2005James I. Hudson Abstract Objective To examine the safety and tolerability of the antidepressant duloxetine across multiple studies for major depressive disorder (MDD). Method Safety data were integrated from the acute phases of eight double-blind, placebo-controlled trials in which patients were randomized to duloxetine (40,120,mg/d; n,=,1139) or placebo (n,=,777) for up to 9 weeks. This data set included all acute-phase clinical trials that formed the basis of the New Drug Application (United States) or European Union submission package for duloxetine in the treatment of MDD. Two studies included continuation phases in which acute treatment responders received duloxetine or placebo for an additional 26 weeks. Safety assessments included serious adverse event reports, rates of discontinuation, spontaneously reported treatment-emergent adverse events, changes in vital signs and laboratory values, and electrocardiograms. Results The rates of serious adverse events for duloxetine- and placebo-treated patients were 0.3% and 0.6%, respectively (p,=,0.282). Adverse events led to discontinuation in 9.7% of duloxetine-treated patients, compared with 4.2% of patients receiving placebo (p,<,0.001). Treatment-emergent adverse events with an incidence for duloxetine ,,5.0% and significantly greater than placebo were nausea, dry mouth, constipation, insomnia, dizziness, fatigue, somnolence, increased sweating and decreased appetite. Mean changes in blood pressure and heart rate were small, and the incidence of increases above normal ranges was low. Duloxetine-treated patients had a mean decrease in weight of 0.5,kg compared with an increase of 0.2,kg for patients receiving placebo (p,<,0.001). No significant differences were found between duloxetine and placebo in the incidence of potentially clinically significant laboratory values at anytime while on treatment. Conclusion These results are consistent with those obtained previously from smaller pooled data sets, and suggest that duloxetine is safe and well tolerated in patients with MDD. Copyright © 2005 John Wiley & Sons, Ltd. [source] Linking Product Development Outcomes to Market Valuation of the Firm: The Case of the U.S. Pharmaceutical Industry,THE JOURNAL OF PRODUCT INNOVATION MANAGEMENT, Issue 5 2004Anurag Sharma The purpose of this research was to examine empirically the effects of new product development outcomes on overall firm performance. To do so, first product development and finance literature were connected to develop three testable hypotheses. Next, an event study was conducted in order to explore whether the changes in the stock market valuation of firms are influenced by the outcomes of efforts to develop new products. The pharmaceutical industry was chosen as the empirical context for the present study's analysis largely because the gate-keeping role played by the Food and Drug Administration (FDA) provides a specific event date on which to focus the event study methodology. As such, this study's events were dates of public announcements of the FDA decisions to approve or to reject the New Drug Applications submitted by the sponsoring firms. Consistent with the efficient market hypothesis, this study's results show that market valuations are responsive strongly and cleanly to the success or failure of new product development efforts. Hence, one of this study's key results suggests that financial markets may be attuned sharply to product development outcomes in publicly traded firms. This study also finds that financial market losses from product development failures were much larger in magnitude than financial market gains from product development successes,indicating an asymmetry in the response of financial markets to the success and failure of new product development efforts. Hence, another implication of this study's results is that managers should factor in a substantial risk premium when considering substantial new development projects. The present study's results also imply that managers should refrain from hyping new products and perhaps even should restrain the enthusiasm that the financial community may build before the product fully is developed. The effect on firm value is severe when expectations about an anticipated new product are not fulfilled. Managers in effect should take care to build reasonable and realistic expectations about potential new products. [source] New pathways for evaluating potential acute stroke therapiesINTERNATIONAL JOURNAL OF STROKE, Issue 2 2006Marc Fisher Many neuroprotective drugs and a few other thrombolytics were evaluated in clinical trials, but none demonstrated unequivocal success and were approved by regulatory agencies. The development paradigm for such therapies needs to provide convincing evidence of efficacy and safety to obtain approval by the Food and Drug Administration (FDA). The FDA modernization act of 1997 stated that such evidence could be derived from one large phase III trial with a clinical endpoint and supportive evidence. Drugs being developed for acute ischemic stroke can potentially be approved under this act by coupling a major phase III trial with supportive evidence provided by a phase IIB trial demonstrating an effect on a relevant biomarker such as magnetic resonance imaging or computed tomography assessment of ischemic lesion growth. Statistical approaches have been developed to optimize the design of such an imaging-based phase IIB study, for example approaches that modify randomization probabilities to assign larger proportions of patients to the ,winning' strategy (i.e. ,pick the winner' strategies) with an interim assessment to reduce the sample size requirement. Demonstrating a treatment effect on a relevant imaging-based biomarker should provide supportive evidence for a new drug application, if a subsequent phase III trial with a clinical outcome demonstrates a significant treatment effect. [source] An "Omics" view of drug developmentDRUG DEVELOPMENT RESEARCH, Issue 2 2004Russ B. Altman Abstract The pharmaceutical industry cannot be blamed for having a love/hate relationship with the fields of pharmacogenetics and pharmacogenomics. At the same time that pharmacogenetics and pharmacogenomics promise to save pipeline drugs by identifying subsets of the population for which they work best, they also threaten to increase the complexity of new drug applications, fragment markets, and create uncertainty for prescribers who simply do not understand or have time to master "personalized medicine." Most importantly, the logical case for genetics-specific drug selection and dosing is much more mature than the practical list of drugs for which outcomes are demonstrably improved. Understandably, pharmaceutical developers and regulators have been careful in creating strategies for using genetics in drug development, and only recently has the FDA begun to establish preliminary rules for pharmacogenetic testing. A growing public academic effort in pharmacogenetics and pharmacogenomics is helping flesh out the basic science underpinnings of the field, and this should combine with extensive efforts of industry to create a solid foundation for future use of genetics in drug development. Two grand challenges to accelerate our capabilities include the characterization of all human genes involved in the basic pharmacokinetics of drugs, and the detailed study of the genes and pathways associated with G-protein-coupled receptors and how they are affected by genetic variation. Drug Dev. Res. 62:81,85, 2004. © 2004 Wiley-Liss, Inc. [source] | ||||||||||