Shumaker R.C.,Clinical Pharmacology and Translational Medicine |
Zhou M.,iCardiac Technologies |
Ren M.,Clinical Pharmacology and Translational Medicine |
Fan J.,Clinical Pharmacology and Translational Medicine |
And 4 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2014
Purpose: QT assessment of oncology drugs is generally challenging because they are genotoxic and, of necessity, they require multisite evaluation in cancer patients. Lenvatinib is not genotoxic, therefore, this thorough QT (TQT) study with lenvatinib, a multityrosine kinase inhibitor, was undertaken utilizing healthy volunteers and concentration-effect modeling to project the TQT effect at high plasma levels. Methods: Fifty-two healthy subjects randomly received single doses of lenvatinib 32 mg, placebo, or moxifloxacin 400 mg in a three-way crossover study. Serial electrocardiograms were recorded, and the effect on placebo-corrected change-from-baseline QTcF (ΔΔQTcF) was evaluated. The relationship between lenvatinib plasma concentrations and QTcF was analyzed with linear mixed-effects modeling. Results: Lenvatinib mildly lowered the heart rate by 5-8 bpm during the first 12 h after dosing. ΔΔQTcF was shortened with a peak effect of -5.72 ms (90 % confidence interval (90 % CI) -7.76 to -3.69 ms) at 6 h postdosing. The upper bound of mean ΔΔQTcF did not exceed 2 ms at any time point postdosing. A concentration-dependent effect of lenvatinib on ΔΔQTcF was identified with an estimated population intercept of -2.96 ms (90 % CI -4.49 to -1.43 ms; P = 0.0016) and a negative slope of -0.0045 (90 % CI -4.49 to -1.43) ms per ng/mL, respectively. The safety profile after a single dose of lenvatinib was acceptable, with adverse events (AEs) of mild-to-moderate severity and no serious AEs. Conclusions: Lenvatinib had no clinically relevant effect on the QTc interval. Concentration-effect modeling supports the lack of QTc prolongation at high plasma concentrations. © 2014 Springer-Verlag.
News Article | October 28, 2016
NDA Partners announced today that Carl Peck, MD, founder and Chairman of the company, will receive the Sheiner–Beal Pharmacometrics Award at the 118th Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics (ASCPT), March 15–18, 2017, in Washington, D.C. The Sheiner–Beal award honors the memory of the pioneering contributions of Drs. Lewis B. Sheiner and Stuart Beal to the scientific discipline of pharmacometrics by recognizing outstanding achievements at the forefront of research or leadership in pharmacometrics and/or application of pharmacometric concepts and techniques to enhance research, development, regulatory evaluation, and/or utilization of therapeutic products. Dr. Sheiner was a founder and highly regarded Partner in NDA Partners before his sudden passing in 2004. “I am especially honored to receive this award as it is named after my mentors and very good friends, Professors Lewis Sheiner and Stuart Beal”, said Dr. Peck”. “Lewis, who we lost in 2004, is recognized as the founder of the field of pharmacometrics, and was a pioneer in the application of modeling and simulation of clinical trials and the introduction of the ‘Learn and Confirm’ paradigm into contemporary drug development.” As a Colonel in the US Army Medical Department, Dr. Peck founded and directed the Division of Clinical Pharmacology as Professor, Departments of Medicine and Pharmacology, Uniformed Services University, Bethesda, Maryland during 1980 to 1987. In 1987, FDA Commissioner Frank Young, appointed Dr. Peck to be Director, Center for Drug Evaluation & Research (CDER), a national leadership position he held until his retirement from government service in 1993. He was promoted to Assistant Surgeon General of the United States in the Public Health Service in October 1990. During 1994, Dr. Peck lectured as “Boerhaave” Professor of Clinical Drug Research at Leiden University (The Netherlands). Dr. Peck was the founding Director of the Center for Drug Development Science at Georgetown University Medical Center, where he served as Professor of Pharmacology from 1994 to 2003. In 1999, Commissioner Henney presented Dr. Peck with the FDA Distinguished Alumnus Award. Sweden’s University of Uppsala conferred an Honorary Doctorate degree (Doctor Honoris Causa) in January 2002 in recognition of "outstanding contributions to the science of drug development." In 2012, he received the Gary Neal Prize for Innovation in Drug Development. Appointed Adjunct Professor in the Department of Bioengineering and Therapeutic Sciences at the University of California at San Francisco (UCSF) in 2004, Dr. Peck and colleagues founded the ongoing UCSF American Course in Drug Development and Regulatory Science in 2007. Dr. Peck is an author of more than 150 original research papers, chapters and books. He serves on numerous scientific advisory boards to academic, industry and government institutions, and is a member of several boards of directors. About ASCPT The American Society for Clinical Pharmacology and Therapeutics (ASCPT) was founded in 1900, and consists of over 2,200 professionals whose primary interest is to advance the science and practice of clinical pharmacology and translational medicine for the therapeutic benefit of patients and society. ASCPT is the largest scientific and professional organization serving the disciplines of Clinical Pharmacology and Translational Medicine. About NDA Partners NDA Partners is a strategy consulting firm specializing in expert product development and regulatory advice to the medical products industry and associated service industries such as law firms, investment funds and government research agencies. The highly experienced Principals and Premier Experts of NDA Partners include three former FDA Center Directors; the former Chairman of the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK; an international team of more than 100 former pharmaceutical industry and regulatory agency senior executives; and an extensive roster of highly proficient experts in specialized areas including nonclinical development, toxicology, pharmacokinetics, CMC, medical device design control and quality systems, clinical development, regulatory submissions, and development program management. Services include product development and regulatory strategy, expert consulting, high-impact project teams, and virtual product development teams.