Assessing acute systemic effects of an inhaled drug with serial echocardiography: a placebo-controlled comparison of inhaled and intravenous dihydroergotamine.
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2013
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Abstract
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.
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Noveck, Robert J, Pamela S Douglas, Shein-Chung Chow, Barry Mangum, Shashidhar Kori and Donald J Kellerman (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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Pamela Susan Douglas
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 of imaging in clinical care, clinical trials and registries and through development and dissemination of national standards for imaging utilization, informatics and analysis. She has been among the pioneers in a number of areas including heart disease in women, sports cardiology, and cardio-oncology. Dr. Douglas’ wealth of experience includes authorship of over 400 peer reviewed manuscripts and 30 practice guidelines, and service as the President of the American College of Cardiology, President of the American Society of Echocardiography, and Chief of Cardiology at both the University of Wisconsin and Duke University. She has also previously served on the faculties of the University of Pennsylvania and Harvard University. She currently serves on the External Advisory Council of the National Heart, Lung and Blood Institute and the Scientific Advisory Board of the Patient Advocate Foundation.
Shein-Chung Chow
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 am also interested in methodology development for statistical evaluation of traditional Chinese medicine (TCM) clinical trials.
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