Larazotide

Overview

Larazotide is a synthetic linear octapeptide (Gly-Gly-Val-Leu-Val-Gln-Pro-Gly) structurally derived from the Vibrio cholerae zonula occludens toxin. It is proposed to act on the zonulin/tight-junction signaling pathway, interrupting gliadin-triggered intestinal barrier disruption by preserving tight-junction integrity locally in the gut lumen. Larazotide has been studied in multiple human trials for celiac disease under the development codes AT-1001, INN-202, and SPD550, but has never received FDA or EMA approval; a Phase 3 trial (NCT03569007) was terminated by the sponsor in 2022 with no results posted. It is not systemically absorbed and is available only as a research chemical.

Mechanism of Action

Larazotide is proposed to act on the zonulin/tight-junction signaling pathway, interrupting the gliadin-triggered cascade: gliadin exposure leads to zonulin release, which signals (via proposed EGFR/PAR2 pathways) on intestinal epithelium, causing downstream phosphorylation and disassembly of tight-junction proteins (claudins, occludin, ZO-1) and actin/myosin cytoskeletal rearrangement, resulting in increased paracellular permeability. Larazotide is reported to block this pathway upstream of tight-junction opening, preserving barrier integrity locally in the gut lumen. It is not systemically absorbed; in a Phase 1 study, plasma larazotide concentrations were below the assay limit of detection at all timepoints across oral doses up to 36 mg, consistent with local luminal action rather than systemic exposure.

Research Summary

Larazotide has been studied in multiple completed human trials for celiac disease but has never received FDA or EMA approval. A Phase 1 single-dose study (Paterson et al. 2007, PMID 17697209) confirmed no systemic absorption. Phase 2 gluten-challenge trials (Leffler et al. 2012, PMID 22825365, n=86, doses 0.25/1/4/8 mg TID) did not meet the primary endpoint (intestinal permeability) due to high variability, though lower doses limited symptom worsening. A Phase 2b trial (Leffler et al. 2015, PMID 25683116, ~342 patients, no gluten challenge) met its primary endpoint at the 0.5 mg TID dose, showing symptom improvement versus placebo with an inverse dose-response. The Phase 3 CeDLara trial (NCT03569007, 307 patients, 0.25 mg and 0.5 mg TID) was terminated by the sponsor in 2022 for futility/impractically large required sample size, with no results posted. Across trials, no serious drug-related adverse events or hepatic/renal/bone toxicity signals were reported; headache and urinary tract infection were the most common adverse events without consistent excess versus placebo. In preclinical models, larazotide reduced gliadin-induced paracellular permeability and preserved tight-junction protein localization in Caco-2 human intestinal cell monolayers, prevented gliadin-induced permeability increases and reduced macrophage infiltration in HLA-DQ8 transgenic mice, and accelerated barrier recovery in a porcine jejunum ischemia-reperfusion injury model.

Vendors selling Larazotide

Scored vendors carrying Larazotide, ranked by trust grade. Grades are computed from indexed Certificates of Analysis. Full $/mg pricing is on the comparison page.

Prescribers who offer Larazotide

4 prescribers in our directory work with Larazotide, each confirmed from their own website. Peptides like Larazotide require a prescription from a licensed provider — telehealth options are available.

Reported Side Effects

• Headache (most common adverse event across trials, no consistent excess vs placebo)
• Urinary tract infection (most common adverse event across trials, no consistent excess vs placebo)
• No serious drug-related adverse events reported in pooled trials
• No hepatic, renal, or bone toxicity signals observed
• Phase 3 trial terminated for futility, not safety

Compare Larazotide with Others

Research References

• Larazotide Acetate, PubChem CID 44146842.
• Larazotide, PubChem CID 9810532.
• The potential utility of tight junction regulation in celiac disease: focus on larazotide acetate. 2016.
• The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study. 2007. PMID 17697209.

Frequently asked questions

Has Larazotide been independently lab-tested?

Disclosed Labs has collected 1 Certificate of Analysis (COA) for Larazotide from 1 independent testing lab. 1 vendor has submitted material for testing. Products average 98.3% tested purity across the corpus. Full testing data is available at https://www.disclosedlabs.com/peptides/larazotide/testing.

Where can researchers source Larazotide?

1 vendor with Disclosed Labs trust grades currently list Larazotide, including Kimera Chems. Compare live prices and lab-verified COAs at https://www.disclosedlabs.com/prices/larazotide.

Which prescribers offer Larazotide with a prescription?

4 prescribers in the Disclosed Labs directory work with Larazotide, each confirmed from their own website, with telehealth options available. Larazotide requires a prescription from a licensed provider. Browse them at https://www.disclosedlabs.com/prescribers?peptide=Larazotide.

How does Larazotide work?

Larazotide is proposed to act on the zonulin/tight-junction signaling pathway, interrupting the gliadin-triggered cascade: gliadin exposure leads to zonulin release, which signals (via proposed EGFR/PAR2 pathways) on intestinal epithelium, causing downstream phosphorylation and disassembly of tight-junction proteins (claudins, occludin, ZO-1) and actin/myosin cytoskeletal rearrangement, resulting in increased paracellular permeability. Larazotide is reported to block this pathway upstream of tight-junction opening, preserving barrier integrity locally in the gut lumen. It is not systemically absorbed; in a Phase 1 study, plasma larazotide concentrations were below the assay limit of detection at all timepoints across oral doses up to 36 mg, consistent with local luminal action rather than systemic exposure.

What does the research say about Larazotide?

Larazotide has been studied in multiple completed human trials for celiac disease but has never received FDA or EMA approval. A Phase 1 single-dose study (Paterson et al. 2007, PMID 17697209) confirmed no systemic absorption. Phase 2 gluten-challenge trials (Leffler et al. 2012, PMID 22825365, n=86, doses 0.25/1/4/8 mg TID) did not meet the primary endpoint (intestinal permeability) due to high variability, though lower doses limited symptom worsening. A Phase 2b trial (Leffler et al. 2015, PMID 25683116, ~342 patients, no gluten challenge) met its primary endpoint at the 0.5 mg TID dose, showing symptom improvement versus placebo with an inverse dose-response. The Phase 3 CeDLara trial (NCT03569007, 307 patients, 0.25 mg and 0.5 mg TID) was terminated by the sponsor in 2022 for futility/impractically large required sample size, with no results posted. Across trials, no serious drug-related adverse events or hepatic/renal/bone toxicity signals were reported; headache and urinary tract infection were the most common adverse events without consistent excess versus placebo. In preclinical models, larazotide reduced gliadin-induced paracellular permeability and preserved tight-junction protein localization in Caco-2 human intestinal cell monolayers, prevented gliadin-induced permeability increases and reduced macrophage infiltration in HLA-DQ8 transgenic mice, and accelerated barrier recovery in a porcine jejunum ischemia-reperfusion injury model.