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Moore S.S.,Abbott Laboratories | Moore S.S.,University of Limerick | Villaumie J.,Actavis
Journal of Raman Spectroscopy | Year: 2015

Drug content of coronary stents is destructively evaluated using high pressure liquid chromatography. The method involves the dissolution of the coating from the stent into a solution and the analysis and quantification of the solvents' drug content. Quantification of the components of drug by Raman has been demonstrated with most recent methods using multivariate techniques. However, the calibration models generated as part of these methods are not easily transferable because they are developed using defined mixtures. In this work, we demonstrate a transferable non-destructive Raman method for the evaluation and quantification of the drug coating components by developing a model from the pure samples of the coating constituents. Using the designed experiment, the transferable Raman method is equivalence tested with the standard high pressure liquid chromatography approach and compares favorably as a non-destructive viable alternative. A method of dealing with the microheterogeneity of stent coatings is presented by spectral sample collection through the rotation of the stent. Knowledge of the coating formation and substrates is required in order to correctly interpret the results. © 2015 John Wiley and Sons, Ltd.

Chen S.,Actavis | Swallow E.,Analysis Group | Li N.,Analysis Group | Faust E.,Analysis Group | And 3 more authors.
Current Medical Research and Opinion | Year: 2015

Objectives: To assess the association between medical costs and persistence with beta blockers among hypertensive patients, and to quantify persistence related medical cost differences with nebivolol, which is associated with improved tolerability, versus other beta blockers. Methods: Adults who initiated hypertension treatment with a beta blocker were identified from the MarketScan∗ claims database (2008-2012). Patients were classified based on their first beta blocker use: nebivolol, atenolol, carvedilol, metoprolol, and other beta blockers. Patients with compelling indications for atenolol, carvedilol or metoprolol (acute coronary syndrome and congestive heart failure) were excluded. Patients enrolled in health maintenance organization or capitated point of service insurance plans were also excluded. Persistence was defined as continuous use of the index drug (<60 day gap). The average effect of persistence on medical costs (2012 USD) was estimated using generalized linear models (GLMs). Regression estimates were used to predict medical cost differences associated with persistence between nebivolol and the other cohorts. Results: A total of 587,424 hypertensive patients met the inclusion criteria. Each additional month of persistence with any one beta blocker was associated with $152.51 in all-cause medical cost savings; continuous treatment for 1 year was associated with $1585.98 in all-cause medical cost savings. Patients treated with nebivolol had longer persistence during the 1 year study period (median: 315 days) than all other beta blockers (median: 156-292 days). Longer persistence with nebivolol translated into $305.74 all-cause medical cost savings relative to all other beta blockers. Limitations: The results may not be generalizable to hypertensive patients with acute coronary syndrome or congestive heart failure. Conclusions: Longer persistence with beta blockers for the treatment of hypertension was associated with lower medical costs. There may be greater cost savings due to better persistence with nebivolol than other beta blockers. © 2015 All rights reserved: reproduction in whole or part not permitted.

Pu Y.,Merck And Co. | Goodey A.P.,Merck And Co. | Fang X.,Actavis | Jacob K.,Merck And Co.
Aerosol Science and Technology | Year: 2014

For nasally delivered medications, it is quite a challenge in the formulation development to characterize the deposition pattern in vivo. An in vitro nose model has been developed recently and adopted in our study to compare the deposition pattern of different nasal solution formulations. One low-viscosity nasal solution and five other solutions containing either Avicel or hydroxypropyl methylcellulose (HPMC) as the viscosity enhancers were examined in this study. The viscosity, spray pattern, plume geometry, and droplet size were characterized. The in vitro deposition patterns were assessed using an anatomically correct silicone nasal cast combined with a color-based image-analysis method. The correlations between the formulation variables, the spray characteristics, and the deposition pattern were investigated. The addition of each viscosity enhancer resulted in increasing viscosity, larger droplet size, narrower plume angle, and lesser anterior deposition. However, it appears that the changes in spray characteristics and deposition pattern are influenced heavily by the identity of the viscosity enhancer, rather than merely by the formulation viscosity itself. Although the Avicel additions led to larger increases in the formulation viscosity, the HPMC additions had far greater impact on the spray characteristics and deposition pattern. The formulations with suboptimal deposition patterns, i.e., the formulations with 'forward' or 'backward' dripping, were successfully identified in this study. This in vitro method was able to discriminate between formulations, revealing differences in regional deposition and the tendency of formulations to drip. As such, the nasal cast method is recommended as a valuable tool for the development of nasal spray formulations. Copyright © Merck Sharp & Dohme Corp.

Landbloom R.L.,Merck | Mackle M.,Merck | Wu X.,Actavis | Kelly L.,Merck | And 4 more authors.
Journal of Affective Disorders | Year: 2016

Background Asenapine is an atypical antipsychotic for acute treatment of manic or mixed episodes associated with bipolar I disorder in adults. The recommended asenapine starting dose is 10 mg bid with the option to reduce the dose to 5 mg bid if needed due to adverse effects/tolerability. Methods Phase IIIb, international, double-blind, fixed-dose, parallel-group, 3-week placebo-controlled trial of asenapine 5 and 10 mg bid in adults with an acute bipolar I disorder manic or mixed episode. Primary outcome was difference in asenapine versus placebo in mean change from baseline to day 21 in the Young-Mania Rating Scale (YMRS) total score. Others included difference in asenapine versus placebo in the Clinical Global Impression Scale for Bipolar Severity (CGI-BP-S) and rate of YMRS responders. Results Both asenapine doses were statistically superior to placebo in mean change from baseline to day 21 in YMRS total score (-10.9, -14.4, and -14.9 for placebo, asenapine 5 mg bid, 10 mg bid, respectively). Both asenapine doses had statistically superior improvement in mean change in CGI-BP-S score at day 21. Neither asenapine dose had significantly more YMRS responders at day 21 than placebo. Limitations Results may not be generalizable to the entire population with bipolar I disorder owing to strict inclusion criteria. Conclusions This study evaluated, by a fixed-dose design, the efficacy and safety of asenapine versus placebo in patients with bipolar I disorder. Both asenapine 5 and 10 mg bid were efficacious in treating mania associated with bipolar I disorder and were generally well tolerated. © 015 Published by Elsevier B.V.

Mazuski J.E.,University of Washington | Gasink L.B.,Astrazeneca | Armstrong J.,Astrazeneca | Broadhurst H.,Astrazeneca | And 5 more authors.
Clinical Infectious Diseases | Year: 2016

Background. When combined with ceftazidime, the novel non-β-lactam β-lactamase inhibitor avibactam provides a carbapenem alternative against multidrug-resistant infections. Efficacy and safety of ceftazidime-avibactam plus metronidazole were compared with meropenem in 1066 men and women with complicated intra-abdominal infections from 2 identical, randomized, double-blind phase 3 studies (NCT01499290 and NCT01500239). Methods. The primary end point was clinical cure at test-of-cure visit 28-35 days after randomization, assessed by noninferiority of ceftazidime-avibactam plus metronidazole to meropenem in the microbiologically modified intention-to-treat (mMITT) population (in accordance with US Food and Drug Administration guidance), and the modified intention-to-treat and clinically evaluable populations (European Medicines Agency guidance). Noninferiority was considered met if the lower limit of the 95% confidence interval for between-group difference was greater than the prespecified noninferiority margin of -12.5%. Results. Ceftazidime-avibactam plus metronidazole was noninferior to meropenem across all primary analysis populations. Clinical cure rates with ceftazidime-avibactam plus metronidazole and meropenem, respectively, were as follows: mMITT population, 81.6% and 85.1% (between-group difference, -3.5%; 95% confidence interval -8.64 to 1.58); modified intention-to-treat, 82.5% and 84.9% (-2.4%; -6.90 to 2.10); and clinically evaluable, 91.7% and 92.5% (-0.8%; -4.61 to 2.89). The clinical cure rate with ceftazidime-avibactam plus metronidazole for ceftazidime-resistant infections was comparable to that with meropenem (mMITT population, 83.0% and 85.9%, respectively) and similar to the regimen's own efficacy against ceftazidime-susceptible infections (82.0%). Adverse events were similar between groups. Conclusions. Ceftazidime-avibactam plus metronidazole was noninferior to meropenem in the treatment of complicated intra-abdominal infections. Efficacy was similar against infections caused by ceftazidime-susceptible and ceftazidime-resistant pathogens. The safety profile of ceftazidime-avibactam plus metronidazole was consistent with that previously observed with ceftazidime alone. © 2016 The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

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