{"id":"larazotide","name":"Larazotide","aliases":["larazotide acetate","AT-1001","INN-202"],"url":"https://lyoresearch.com/compounds/larazotide","class":{"id":"gut-peptides","name":"Gut and intestinal peptides","url":"https://lyoresearch.com/classes/gut-peptides"},"summary":"Larazotide is a synthetic eight-amino-acid peptide taken by mouth to tighten the junctions between intestinal cells, developed as the first drug for persistent symptoms in coeliac disease despite a gluten-free diet. Its 342-person phase 2b trial met its primary endpoint at the lowest of three doses while the two higher doses did no better than placebo. The phase 3 trial, CeDLara, was stopped in 2022 after an interim analysis showed it was unlikely to succeed. It is not approved anywhere.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"Phase 2b (n=342) positive at one dose; phase 3 (CeDLara) discontinued at interim analysis","regulatory_status":"Investigational (phase 3 discontinued)","molecule":{"formula":"C32H55N9O10","molecular_weight":"725.8","cas":"258818-34-7","pubchem_cid":9810532,"sequence":"GGVLVQPG","sequence_note":null,"note":null},"pharmacokinetics":{"basis":"human","route":"Oral capsule, taken before meals in the trials","half_life":"Not established; larazotide acts in the intestinal lumen and is not meaningfully absorbed","licensed_regimen":null,"product":null,"source":{"title":"Larazotide phase 2b trial (Gastroenterology, 2015)","url":"https://pubmed.ncbi.nlm.nih.gov/25683116/"}},"outcomes":[{"outcome":"Coeliac symptoms on a gluten-free diet","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"1 phase 2b RCT (n=342, 12 wk)","evidence":"In a 12-week trial of 342 adults with coeliac disease and persistent symptoms despite a gluten-free diet, the lowest of three doses reduced symptoms against placebo on the primary endpoint. The two higher doses did not. An unexplained inverse dose–response in a single phase 2b is weak ground, and the confirmatory trial did not confirm it.","references":[{"citation":"Leffler DA, Kelly CP, Green PH, et al. Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial.","where":"Gastroenterology, 2015;148:1311–1319","url":"https://pubmed.ncbi.nlm.nih.gov/25683116/"}],"verbatim":{"text":"The primary end point was met with the 0.5-mg dose of larazotide acetate, with fewer symptoms compared with placebo by modified intention to treat (n = 340) (analysis of covariance, P = .022; mixed model for repeated measures, P = .005).","citation":"Leffler DA, Kelly CP, Green PH, et al. Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial.","url":"https://pubmed.ncbi.nlm.nih.gov/25683116/"}},{"outcome":"Dose–response","grade":"C","grade_meaning":"weak human evidence","effect_size":"not measurable","adverse":false,"human_studies":"1 phase 2b RCT (n=342)","evidence":"The higher doses were flat. Where a drug's effect does not increase with dose, the most parsimonious explanation for a single positive arm is chance.","references":[{"citation":"Leffler DA, Kelly CP, Green PH, et al. Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial.","where":"Gastroenterology, 2015;148:1311–1319","url":"https://pubmed.ncbi.nlm.nih.gov/25683116/"}],"verbatim":{"text":"The 1- and 2-mg doses were no different than placebo for any end point.","citation":"Leffler DA, Kelly CP, Green PH, et al. Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial.","url":"https://pubmed.ncbi.nlm.nih.gov/25683116/"}},{"outcome":"Confirmation in phase 3","grade":"A","grade_meaning":"established in humans","effect_size":"not measurable","adverse":false,"human_studies":"1 phase 3 RCT stopped at interim analysis","evidence":"CeDLara, the registrational phase 3 trial, was discontinued in June 2022 after a pre-specified interim analysis of roughly half of a planned 525 patients: the sponsor said the number of additional patients needed to show an effect was too large to support continuing. A futility stop is a negative result, and graded on the strength of the design rather than the direction of the finding.","references":[{"citation":"9 Meters Biopharma. Discontinuation of the phase 3 CeDLara trial of larazotide in celiac disease following interim analysis.","where":"Press release, 21 Jun 2022 (SEC exhibit 99.1)","url":"https://www.sec.gov/Archives/edgar/data/1551986/000155198622000046/ex-991pressreleasedated621.htm"}]},{"outcome":"Safety","grade":"C","grade_meaning":"weak human evidence","effect_size":"not measurable","adverse":true,"human_studies":"Phase 2 programme","evidence":"Tolerability across the phase 2 programme was broadly similar to placebo; larazotide is not absorbed to any meaningful extent and acts in the gut lumen. Safety was never the obstacle.","references":[]}],"regions":[{"region":"European Union","status":"Not authorised","note":"Investigational; no marketing authorisation."},{"region":"United States","status":"Not approved","note":"Investigational. Development discontinued after the 2022 interim analysis of the phase 3 trial. Products sold under the name are not the trial drug."},{"region":"United Kingdom","status":"Not licensed","note":"No MHRA licence."},{"region":"Australia","status":"Not on the ARTG","note":"Investigational only."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Unapproved anywhere, so S0 (non-approved substances)."}],"faq":[{"q":"Is larazotide a treatment for coeliac disease?","a":"No. It is the furthest any drug has got — a positive phase 2b at one dose — and its phase 3 trial was stopped in 2022 because it was unlikely to succeed. A gluten-free diet remains the only treatment."},{"q":"Does larazotide fix \"leaky gut\"?","a":"It was designed to tighten intestinal junctions, and the preclinical work supports that mechanism. No controlled human trial has tested it for anything other than coeliac symptoms, and that programme ended."},{"q":"Why did the phase 3 trial stop?","a":"A pre-specified interim analysis at about half enrolment found the effect too small to reach significance without far more patients than the trial could recruit. That is a futility stop, not a safety stop."}],"references":[{"cite":"Leffler DA, Kelly CP, Green PH, et al. Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial.","where":"Gastroenterology, 2015;148:1311–1319","url":"https://pubmed.ncbi.nlm.nih.gov/25683116/","note":"342 randomised; 12 weeks; three doses versus placebo. Primary endpoint met at the lowest dose only."},{"cite":"9 Meters Biopharma. Discontinuation of the phase 3 CeDLara trial of larazotide in celiac disease following interim analysis.","where":"Press release, 21 Jun 2022 (SEC exhibit 99.1)","url":"https://www.sec.gov/Archives/edgar/data/1551986/000155198622000046/ex-991pressreleasedated621.htm","note":"Interim analysis covered about half of a planned 525 patients; the release says the number of additional patients needed was too large to support trial continuation. NCT03569007."},{"cite":"PubChem compound record: larazotide.","where":"PubChem, read 29 Oct 2026","url":"https://pubchem.ncbi.nlm.nih.gov/compound/9810532","note":"Formula, molecular weight, CAS and the GGVLVQPG sequence used on this page."}],"last_reviewed":"2026-10-29","literature_searched_to":"2026-10-29","changelog":[{"date":"2026-10-29","note":"Initial publication. Grade C: phase 2b positive at one dose only, phase 3 stopped for futility in 2022."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}