Volume 148, Issue 7, Pages 1311-1319.e6 (June 2015) Larazotide Acetate for Persistent Symptoms of Celiac Disease Despite a Gluten-Free Diet: A Randomized Controlled Trial  Daniel A. Leffler, Ciaran P. Kelly, Peter H.R. Green, Richard N. Fedorak, Anthony DiMarino, Wendy Perrow, Henrik Rasmussen, Chao Wang, Premysl Bercik, Natalie M. Bachir, Joseph A. Murray  Gastroenterology  Volume 148, Issue 7, Pages 1311-1319.e6 (June 2015) DOI: 10.1053/j.gastro.2015.02.008 Copyright © 2015 AGA Institute Terms and Conditions

Figure 1 Primary end point: average on-treatment scores on the CeD-GSRS. The 0.5-mg larazotide acetate dose met the primary end point. Gastroenterology 2015 148, 1311-1319.e6DOI: (10.1053/j.gastro.2015.02.008) Copyright © 2015 AGA Institute Terms and Conditions

Figure 2 Larazotide acetate 0.5 mg 3 times per day reduced the average on-treatment weekly number of CeD PRO symptomatic days. Symptomatic days defined a priori as a day with a mean score of ≥3 on either the abdominal symptom or diarrhea/loose stool domains. Gastroenterology 2015 148, 1311-1319.e6DOI: (10.1053/j.gastro.2015.02.008) Copyright © 2015 AGA Institute Terms and Conditions

Supplementary Figure 1 Study design and patient disposition. Gastroenterology 2015 148, 1311-1319.e6DOI: (10.1053/j.gastro.2015.02.008) Copyright © 2015 AGA Institute Terms and Conditions

Supplementary Figure 2 Tight junction structure and mechanism of action of larazotide acetate. Larazotide acetate is a TJ regulator octapeptide inhibitor of Vibrio cholera zonula occludens (ZO) toxin. TJs comprise more than 50 proteins, including the transmembrane proteins occluding claudin, junctional adhesion molecule (JAM), and cytoplasmic scaffolding proteins ZO-1, ZO-2, and ZO-3. Larazotide acetate inhibits the cytoskeletal rearrangement and ZO-1 redistribution caused by gliadin in epithelial cells regulates actin rearrangement and stabilizes TJ in vitro in response to various stimuli, including inflammatory cytokines, bacterial products, and gliadin. In addition, larazotide acetate inhibits transepithelial gliadin transport in vitro and decreases intestinal permeability and preserves barrier function in vitro and in vivo. Reprinted with permission from Martinez et al. Cellular and molecular basis of intestinal barrier dysfunction in the irritable bowel syndrome. Gut Liver 2012;6:305–315. © Korean Association of Medical Journal Editors. http://gutnliver.org. Gastroenterology 2015 148, 1311-1319.e6DOI: (10.1053/j.gastro.2015.02.008) Copyright © 2015 AGA Institute Terms and Conditions

Supplementary Figure 3 No increase or worsening of serum antibody levels. Gastroenterology 2015 148, 1311-1319.e6DOI: (10.1053/j.gastro.2015.02.008) Copyright © 2015 AGA Institute Terms and Conditions