Core Aspects of Clinical Development and Trials in Chronic Idiopathic Constipation

Randall T. Brown, MD, Megan Zuelsdorff, BS, Michael Fleming, MD, MPH, Adverse effects and cognitive function among primary care patients taking opioids for chronic nonmalignant pain. Journal of opioid management. ,vol. 2, pp. 137- 146 ,(2006) , 10.5055/JOM.2006.0023

Michael D Crowell, Lucinda A Harris, Linaclotide, a new direction in the treatment of irritable bowel syndrome and chronic constipation Current Opinion in Molecular Therapeutics. ,vol. 9, pp. 403- 410 ,(2007)

R. S. CHOUNG, G. R. LOCKE III, C. D. SCHLECK, A. R. ZINSMEISTER, N. J. TALLEY, Cumulative incidence of chronic constipation: a population-based study 1988–2003 Alimentary Pharmacology & Therapeutics. ,vol. 26, pp. 1521- 1528 ,(2007) , 10.1111/J.1365-2036.2007.03540.X

William D. Chey, Anthony Lembo, James E. MacDougall, Bernard J. Lavins, Harvey Schneier, Jeffrey M. Johnston, Efficacy and Safety of Once-Daily Linaclotide Administered Orally for 26 Weeks in Patients With IBS-C: Results From a Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial Gastroenterology. ,vol. 140, ,(2011) , 10.1016/S0016-5085(11)60550-7

Nilay D. Shah, Denesh K. Chitkara, G. Richard Locke, Patrick D. Meek, Nicholas J. Talley, Ambulatory care for constipation in the United States, 1993-2004. The American Journal of Gastroenterology. ,vol. 103, pp. 1746- 1753 ,(2006) , 10.1111/J.1572-0241.2008.01910.X

J. H. De Maeyer, R. A. Lefebvre, J. A. J. Schuurkes, 5‐HT4 receptor agonists: similar but not the same Neurogastroenterology and Motility. ,vol. 20, pp. 99- 112 ,(2008) , 10.1111/J.1365-2982.2007.01059.X

Andrew G. Spencer, Jeffrey W. Jacobs, Michael R. Leadbetter, Christopher W. Carreras, Xunxiang Du, Noah Bell, Samantha Koo-McCoy, Jill N. Kohler, Eric Labonté, David P. Rosenbaum, Marc Navre, Dominique Charmot, RDX5791, a First-in-Class Minimally Systemic NHE3 Inhibitor in Clinical Development for CIC and IBS-C, Increases Intestinal Sodium Leading to Enhanced Intestinal Fluid Volume and Transit Gastroenterology. ,vol. 140, ,(2011) , 10.1016/S0016-5085(11)60405-8

J. Tack, S. Müller-Lissner, V. Stanghellini, G. Boeckxstaens, M. A. Kamm, M. Simren, J.-P. Galmiche, M. Fried, Diagnosis and treatment of chronic constipation – a European perspective Neurogastroenterology and Motility. ,vol. 23, pp. 697- 710 ,(2011) , 10.1111/J.1365-2982.2011.01709.X

Anthony Lembo, Harvey Schneier, Bernard J. Lavins, Steven J. Shiff, James E. MacDougall, Xinwei D. Jia, Jeffrey M. Johnston, The Effect of Linaclotide on Measures of Abdominal and Bowel Symptoms in Patients With Chronic Constipation and Abdominal Pain: Pooled Results From Two Phase 3 Trials Gastroenterology. ,vol. 140, ,(2011) , 10.1016/S0016-5085(11)60198-4

M. Goldberg, Y.-P. Li, J. F. Johanson, A. W. Mangel, M. Kitt, D. T. Beattie, K. Kersey, O. Daniels, Clinical trial: the efficacy and tolerability of velusetrag, a selective 5-HT4 agonist with high intrinsic activity, in chronic idiopathic constipation - a 4-week, randomized, double-blind, placebo-controlled, dose-response study. Alimentary Pharmacology & Therapeutics. ,vol. 32, pp. 1102- 1112 ,(2010) , 10.1111/J.1365-2036.2010.04456.X