Larazotide acetate (development code AT-1001) is a synthetic peptide eight amino acids long, taken by mouth, that was designed to tighten the seals between cells lining the small intestine. It was developed as an add-on to a gluten-free diet for people with celiac disease, the autoimmune condition in which gluten damages the small intestine. It is not an anabolic or performance drug.

The single most important fact: larazotide never reached approval. Its phase 3 trial, CedLara, was stopped in June 2022 after an interim analysis showed that the number of extra patients needed to prove a benefit over placebo was too large. The sponsor, 9 Meters Biopharma, then discontinued development in celiac disease (9 Meters press release, June 2022; 9 Meters Q2 2022 release).

This page summarizes what the clinical trials, the trial registry and the sponsor’s regulatory filings report. It is for education only and is not medical advice.

Property	Detail
Class	Synthetic 8-amino-acid peptide; investigational intestinal tight junction regulator
Other names	AT-1001, INN-202, NM-001
Developers	Alba Therapeutics, then Innovate Biopharmaceuticals (IND transferred 2016), which merged to form 9 Meters Biopharma
Route	Oral; enteric-coated beads in capsules, released in the duodenum
Doses studied	0.25–8 mg three times daily in phase 2; 0.25 and 0.5 mg three times daily in phase 3
Half-life	Not established in humans: plasma levels stayed below the 0.5 ng/mL detection limit. In pigs, ≈ 0.65–0.76 h in intestinal fluid
Formula (PubChem)	Peptide C32H55N9O10, 725.8 g/mol; acetate salt C34H59N9O12, 785.9 g/mol
US status	Not FDA-approved. Had FDA Fast Track designation for celiac disease; celiac development discontinued in 2022
WADA status	Not named on the 2026 list; the S0 class covers substances with no human therapeutic approval

What it is

Larazotide is a single-chain peptide of eight amino acids (Slifer et al., Am J Physiol 2021; PubChem). Its structure was derived from zonula occludens toxin (Zot), a protein made by the cholera bacterium Vibrio cholerae that loosens the junctions between intestinal cells (Paterson et al., Aliment Pharmacol Ther 2007; Gopalakrishnan et al., Peptides 2012). It was found by screening synthetic peptides related to that toxin (Leffler et al., Gastroenterology 2015). The drug is supplied as the acetate salt, hence the name.

The idea behind it: tight junctions are protein seals that control what passes between cells of the gut lining. In celiac disease, gluten fragments are thought to cross this barrier more easily and then trigger the immune reaction. A drug that keeps the junctions closed might reduce how much gluten reaches the immune system.

The proposed mechanism comes mostly from cell and animal work:

In cell culture, larazotide blocked the rearrangement of the junction protein ZO-1 and of actin caused by gliadin (a gluten protein) and by a Zot-derived peptide, and reduced passage of a gliadin fragment across a cell layer (Gopalakrishnan et al., Peptides 2012).
In transgenic mice sensitized to gliadin, it reduced macrophage build-up in the intestine and preserved normal junction structure (same study).
Zonulin and other targets. Larazotide is often described as a zonulin antagonist, and later work also linked it to inhibition of myosin light chain kinase (Slifer et al., 2021). The zonulin link is contested: a 2021 letter in Gut by two immunologists was titled “Lack of relationship of AT1001 to zonulin and prehaptoglobin-2” (Sollid and Koning, Gut 2021).

How it behaves in the body

Larazotide is meant to act locally in the gut, not in the bloodstream. The capsules contain enteric-coated beads that pass the stomach. Part of the dose is released on entry into the duodenum and the rest about 30 minutes later (9 Meters 10-K, 2022).

There is no human pharmacokinetic profile, because the drug could not be measured in blood:

Study	Dose	Plasma finding
Phase 2 gluten challenge, 14 days (Leffler et al., Am J Gastroenterol 2012)	0.25, 1, 4 or 8 mg three times daily	Larazotide below the 0.5 ng/mL limit of quantification in all groups; metabolites (8 mg group) also below the limit
Phase 1 single dose, as summarized by later authors (Enomoto et al., PLoS One 2021)	12 mg	All plasma concentrations below 0.5 ng/mL

The only concentration-time data come from pigs. In three healthy pigs given 1 mg of the delayed-release formulation, larazotide peaked in intestinal fluid at 1 hour in the distal duodenum and proximal jejunum. The mean elimination half-life in intestinal fluid was 0.65 h (duodenum) and 0.76 h (jejunum) (Enomoto et al., PLoS One 2021). The authors note that the peptide is broken down in the small intestine and that its pharmacokinetics have not been described in people.

Regulatory and development history

August 12, 2005. Alba Therapeutics filed the first IND (investigational new drug application) for larazotide in celiac disease. The IND moved to Innovate Biopharmaceuticals on March 8, 2016 (9 Meters 10-K, 2021).
Fast Track. FDA granted larazotide Fast Track designation for celiac disease, a program that allows more frequent FDA contact and rolling review. It is not an approval (same filing).
May 2019. The phase 3 CedLara trial (NCT03569007) began (ClinicalTrials.gov).
June 2022. An interim analysis did not support continuing the trial (9 Meters press release, June 2022).
August 2022. 9 Meters announced it was discontinuing development of larazotide in celiac disease (9 Meters Q2 2022 release).

No regulator has approved larazotide for any use.

What the research shows

Early gluten-challenge trials

In these trials, people with well-controlled celiac disease on a gluten-free diet were deliberately given gluten to see whether larazotide blunted the reaction.

Trial	Design and n	Doses	Main findings
Paterson et al., 2007	Inpatient, double-blind, randomized, placebo-controlled	12 mg single doses	No increase in adverse events. Intestinal permeability rose 70% on placebo after gluten, none on drug. GI symptoms more frequent on placebo (p = 0.018)
Leffler et al., 2012	Randomized, double-blind; 86 patients; 14 days; 2.4 g gluten/day	0.25, 1, 4, 8 mg three times daily	Primary endpoint (urine lactulose/mannitol permeability test) too variable to assess; no significant difference. Some lower doses limited gluten-induced symptoms; the highest dose did not
Kelly et al., 2013	Randomized, double-blind; 184 patients; 6 weeks; 2.7 g gluten/day	1, 4, 8 mg three times daily	No difference in permeability. 1 mg limited gluten-induced symptoms (p = 0.002). Anti-tissue transglutaminase IgA rose 19.0-fold over baseline on placebo vs 5.78-, 3.88- and 7.72-fold on 1, 4 and 8 mg

The permeability test that the drug was designed to change did not separate drug from placebo in either of the two larger trials.

Phase 2b: persistent symptoms despite a gluten-free diet

The largest published trial randomized 342 adults who had followed a gluten-free diet for at least 12 months but still had symptoms (Leffler et al., Gastroenterology 2015). After a 4-week placebo run-in, patients took larazotide 0.5, 1 or 2 mg or placebo three times daily, 15 minutes before meals, for 12 weeks. The primary endpoint was the average on-treatment Celiac Disease Gastrointestinal Symptom Rating Scale (CeD-GSRS) score.

Outcome (0.5 mg vs placebo)	Result
Primary endpoint, CeD-GSRS	Met (ANCOVA p = 0.022; MMRM p = 0.005)
GI symptomatic days per week	1.73 vs 2.38 (26% fewer; p = 0.017)
Improved symptom days per week	2.51 vs 1.99 (31% more; p = 0.034)
Headache and tiredness scores	Lower (MMRM p = 0.010)
Celiac antibody titers	No change or worsening in any group
1 mg and 2 mg doses	No different from placebo on any endpoint

The result was mixed: only the lowest dose worked, and the secondary endpoints based on the CeD PRO abdominal and GI domains (a celiac-specific daily symptom diary) favored 0.5 mg but were not statistically significant. The authors themselves described the results as mixed.

A 2022 meta-analysis pooled 4 randomized trials with 626 patients (Hoilat et al., Clin Res Hepatol Gastroenterol 2022). It found:

no difference from placebo in the lactulose/mannitol permeability ratio;
better symptom scores than placebo during gluten challenge;
no significant symptom difference in patients on a gluten-free diet alone.

Phase 3 CedLara: stopped for futility

CedLara (NCT03569007) was a randomized, double-blind, placebo-controlled phase 3 trial in adults with celiac disease who still had symptoms on a gluten-free diet (ClinicalTrials.gov; 9 Meters press release, June 2022).

Feature	Detail
Arms	Larazotide 0.25 mg, larazotide 0.5 mg, or placebo, three times daily
Planned size	525 patients (175 per arm)
Actual enrollment	307 (registry)
Duration	12-week double-blind treatment, then a 12-week safety phase
Primary endpoint	Change in the CeD PRO abdominal domain score over 12 weeks
Interim analysis	About the first 50% of target enrollment, after the 12-week efficacy phase
Outcome	Additional patients needed to show a significant difference judged “too large to support trial continuation”
Registry status	Terminated by sponsor; completion July 21, 2022

The interim analysis was run by an independent statistician to re-estimate the sample size needed to detect a statistically significant effect. In practice, this means the difference between larazotide and placebo in the first half of patients was too small to be confirmed with a feasible trial size. In its August 2022 earnings release, 9 Meters said it was “discontinuing further development of larazotide in celiac disease” (9 Meters Q2 2022 release).

No effect sizes from CedLara have been published, and the registry entry has no posted results. The 2015 phase 2b signal at 0.5 mg was therefore not confirmed in phase 3.

Other uses studied

Larazotide was later tested as an add-on treatment in multisystem inflammatory syndrome in children (MIS-C), a severe complication that follows COVID-19. A phase 2a randomized, placebo-controlled trial in 12 children (median age 5.7 years) gave it four times daily for 3 weeks (Yonker et al., Sci Transl Med 2025). No larazotide-related adverse events were reported. Treated children had faster resolution of GI symptoms and faster clearance of spike protein from blood, but with 12 patients this is exploratory.

Other studies in arthritis, colitis, liver injury and intestinal ischemia have been in mice, rats or pigs only (Slifer et al., 2021). They do not show benefit in people.

Side effects and risks

Trial safety data

Across the published trials, adverse events on larazotide were similar to placebo:

Phase 1 (12 mg single doses): no increase in adverse events vs placebo (Paterson et al., 2007).
2012 gluten-challenge trial: no serious adverse events; the most common events were headache and urinary tract infection (Leffler et al., 2012).
2013 gluten-challenge trial: adverse event rates similar between larazotide and placebo (Kelly et al., 2013).
2015 phase 2b: safety comparable to placebo at all doses; no significant changes in vital signs, labs or ECGs; no drug-related serious adverse events (Leffler et al., 2015).

The sponsor reported that across seven clinical studies, 5 patients had a serious adverse event (2 on placebo, 3 on larazotide), including gallbladder inflammation, gallstones, depression, an allergic reaction to penicillin and appendicitis. The company did not consider them drug-related (9 Meters 10-K, 2021).

Limits of the safety record

Treatment lasted at most 12 weeks in published trials. Long-term safety is unknown.
Safety data from CedLara have not been published.
No interaction studies have been published.

Not a substitute for a gluten-free diet

Larazotide was only ever tested as an add-on to a gluten-free diet. In the gluten-challenge trials, anti-transglutaminase antibodies still rose on larazotide, only less than on placebo (Kelly et al., 2013). No trial showed that it protects the intestine from regular gluten intake.

Unregulated products

Because larazotide was never approved, any product sold under that name today comes from outside the regulated drug supply. Its identity, purity and dose cannot be assumed, and the trial results above apply only to the enteric-coated formulation used in those studies.

Legal status and sport

United States: investigational drug with no FDA approval.
Sport: larazotide is not named on the WADA list. The S0 class prohibits at all times any pharmacological substance not covered elsewhere on the list that has no current approval by any government health authority for human therapeutic use, including drugs under development or discontinued (WADA 2026 Prohibited List).

Key takeaways

A gut-acting peptide, not an anabolic. Larazotide is an 8-amino-acid peptide derived from a cholera toxin, designed to keep intestinal tight junctions closed in celiac disease.
Barely absorbed. Plasma levels stayed below 0.5 ng/mL in human trials, so no human half-life exists. In pigs its half-life in intestinal fluid was under an hour.
Phase 2 signal was mixed. In 342 patients, only the 0.5 mg dose beat placebo on the primary symptom score; 1 mg and 2 mg did not, and the permeability test never separated from placebo.
Phase 3 failed. CedLara was stopped in June 2022 after an interim analysis judged that proving a benefit would need too many more patients, and development in celiac disease was discontinued.
Clean but short safety record. Adverse events matched placebo in trials of up to 12 weeks; long-term safety is unknown.
Never approved. No regulator has approved larazotide, and it falls under WADA’s S0 class of non-approved substances.

Sources

Paterson BM, Lammers KM, Arrieta MC, Fasano A, Meddings JB. The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study. Aliment Pharmacol Ther. 2007;26(5):757–766. PubMed.
Gopalakrishnan S, Durai M, Kitchens K, et al. Larazotide acetate regulates epithelial tight junctions in vitro and in vivo. Peptides. 2012;35(1):86–94. PubMed.
Leffler DA, Kelly CP, Abdallah HZ, et al. A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge. Am J Gastroenterol. 2012;107(10):1554–1562. PubMed.
Kelly CP, Green PH, Murray JA, et al. Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study. Aliment Pharmacol Ther. 2013;37(2):252–262. PubMed.
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. Gastroenterology. 2015;148(7):1311–1319.e6. PubMed.
Hoilat GJ, Altowairqi AK, Ayas MF, et al. Larazotide acetate for treatment of celiac disease: a systematic review and meta-analysis of randomized controlled trials. Clin Res Hepatol Gastroenterol. 2022;46(1):101782. PubMed.
Enomoto H, Yeatts J, Carbajal L, et al. In vivo assessment of a delayed release formulation of larazotide acetate indicated for celiac disease using a porcine model. PLoS One. 2021;16(4):e0249179. PubMed.
Slifer ZM, Krishnan BR, Madan J, Blikslager AT. Larazotide acetate: a pharmacological peptide approach to tight junction regulation. Am J Physiol Gastrointest Liver Physiol. 2021;320(6):G983–G989. PubMed.
Sollid LM, Koning F. Lack of relationship of AT1001 to zonulin and prehaptoglobin-2: clinical implications. Gut. 2021;70(11):2211–2212. PubMed.
Yonker LM, Kane AS, Swank Z, et al. Viral spike antigen clearance and augmented recovery in children with post-COVID multisystem inflammatory syndrome treated with larazotide. Sci Transl Med. 2025;17(809):eadu4284. PubMed.
9 Meters Biopharma. Study to Evaluate the Efficacy and Safety of Larazotide Acetate for the Relief of CeD Symptoms (CedLara). NCT03569007. ClinicalTrials.gov.
9 Meters Biopharma. 9 Meters Biopharma announces interim analysis of Phase 3 study of larazotide for celiac disease does not support trial continuation. Press release, Form 8-K Exhibit 99.1, June 21, 2022. SEC.
9 Meters Biopharma. Second quarter 2022 financial results and corporate update. Press release, Form 8-K Exhibit 99.1, August 15, 2022. SEC.
9 Meters Biopharma. Annual report on Form 10-K for fiscal year 2021. Filed March 23, 2022. SEC.
9 Meters Biopharma. Annual report on Form 10-K for fiscal year 2022. Filed March 28, 2023. SEC.
National Center for Biotechnology Information. PubChem Compound Summary: Larazotide (CID 9810532) and larazotide acetate (CID 44146842). PubChem.
World Anti-Doping Agency. The 2026 Prohibited List. WADA 2026 Prohibited List.

Larazotide Acetate