Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study
Version of Record online: 19 NOV 2012
© 2012 Blackwell Publishing Ltd
Alimentary Pharmacology & Therapeutics
Volume 37, Issue 2, pages 252–262, January 2013
How to Cite
Kelly, C. P., Green, P. H. R., Murray, J. A., DiMarino, A., Colatrella, A., Leffler, D. A., Alexander, T., Arsenescu, R., Leon, F., Jiang, J. G., Arterburn, L. A., Paterson, B. M., Fedorak, R. N. and the Larazotide Acetate Celiac Disease Study Group (2013), Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study. Alimentary Pharmacology & Therapeutics, 37: 252–262. doi: 10.1111/apt.12147
- Issue online: 17 DEC 2012
- Version of Record online: 19 NOV 2012
- Manuscript Accepted: 29 OCT 2012
- Manuscript Revised: 28 OCT 2012
- Manuscript Revised: 19 OCT 2012
- Manuscript Received: 11 SEP 2012
- Alba Therapeutics Corporation
- Cephalon, Inc.
Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet (GFD), which is difficult for many patients. Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae.
To evaluate the efficacy and tolerability of larazotide acetate during gluten challenge.
This exploratory, double-blind, randomised, placebo-controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run-in, patients were randomised to larazotide acetate (1, 4, or 8 mg three times daily) or placebo and received 2.7 grams of gluten daily for 6 weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels.
No significant differences in LAMA ratios were observed between larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (P = 0.002 vs. placebo). Mean ratio of anti-tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group compared with 5.78 (P = 0.010), 3.88 (P = 0.005) and 7.72 (P = 0.025) in the larazotide acetate 1-, 4-, and 8-mg groups, respectively. Adverse event rates were similar between larazotide acetate and placebo groups.
Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.