Assessing acute systemic effects of an inhaled drug with serial echocardiography: a placebo-controlled comparison of inhaled and intravenous dihydroergotamine.
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OBJECTIVE: MAP0004 is an investigational product which delivers dihydroergotamine (DHE) through the lung via a breath-synchronized metered dose inhaler. The objective of this study was to compare the acute effects of orally inhaled and intravenous (IV) DHE to placebo on maximum change and area under the curve for pulmonary arterial systolic pressure (PASP). RESEARCH DESIGN AND METHODS: A randomized, double-blind, placebo-controlled, 3-period, crossover study of 24 health adults. Trial registration NCT01089062. Study assessments included pharmacokinetics, electrocardiograms (ECG), and validated echocardiographic (Doppler)-derived measures of PASP by echocardiogram. The primary endpoint was the absolute change in calculated PASP using area under the curve, 0 to 2 hours (AUC(0-2h)). RESULTS: The change in PASP with IV DHE was significantly different than MAP0004 and placebo (AUC(0-2h)2857, 2624, and 2453 mmHg*min, respectively). After a second dose of MAP0004, AUC(0-4h) remained lower with MAP0004 than with a single dose of IV DHE. Adverse events were more common with IV DHE than with MAP0004 or placebo. None of the treatments produced clinically significant changes in PASP or other cardiac parameters. Changes in PASP were significantly smaller with MAP0004 compared with IV DHE. CONCLUSION: These results indicate the effects 1 mg of orally inhaled DHE on the cardiovascular system are less than with 1 mg of IV DHE, and that serial echocardiography can be a useful noninvasive means of assessing acute systemic effects.
pulmonary artery systolic pressure
Metered Dose Inhalers
Published Version (Please cite this version)10.2147/DDDT.S44093
Publication InfoNoveck, Robert J; Douglas, Pamela S; Chow, Shein-Chung; Mangum, Barry; Kori, Shashidhar; & Kellerman, Donald J (2013). Assessing acute systemic effects of an inhaled drug with serial echocardiography: a placebo-controlled comparison of inhaled and intravenous dihydroergotamine. Drug Des Devel Ther, 7. pp. 619-625. 10.2147/DDDT.S44093. Retrieved from https://hdl.handle.net/10161/11172.
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Professor of Biostatistics and Bioinformatics
My research interest includes statistical methodology development and application in the area of biopharmaceutical/clinical statistics such as bioavailability and bioequivalence, clinical trials, bridging studies, medical devices, and translational research/medicine. Most recently, I am interested in statistical methodology development for the use of adaptive design methods in clinical trials and methodology development for assessment of biosimilarity of follow-on biologics. In addition, I
Ursula Geller Distinguished Professor for Research in Cardiovascular Disease, in the School of Medicine
Pamela S Douglas MD is the Ursula Geller Professor of Research in Cardiovascular Diseases in the Department of Medicine at Duke University and Director of the Multimodality Imaging Program at Duke Clinical Research Institute. During her 30+ years of experience she has led several landmark multicenter government studies and pivotal industry clinical trials along with outcomes research studies. She is renowned for her scientific and policy work in improving the quality and appropriateness
Associate Professor of Medicine
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