COMPOUND

Compounds / Healing

Larazotide

Larazotide acetate (AT-1001, INN-202)

Healing Oral Not FDA approved

Synthetic 8-amino-acid peptide (Gly-Gly-Val-Leu-Val-Gln-Pro-Gly) derived from research on Vibrio cholerae zonula occludens toxin. Acts as a zonulin receptor antagonist and tight junction regulator: closes 'leaky' intestinal tight junctions to reduce paracellular permeability. Originally developed for celiac disease (as adjunct to gluten-free diet). IMPORTANT: 9 Meters Biopharma's CeDLara phase 3 trial was DISCONTINUED in June 2022 for futility: the pivotal trial failed to meet its primary endpoint. Despite the failed phase 3, larazotide remains in active biohacker community use for 'leaky gut' and IBD-adjacent symptoms; sourced from research-peptide vendors as oral tablets / capsules.

At a glance

Routes
Oral
Vial sizes
0.25 mg · 0.5 mg · 1 mg
Evidence base
3 studies 3 human

Mechanism

Antagonizes zonulin (haptoglobin-2 precursor) at the tight-junction receptor, preventing the occludin / ZO-1 / claudin-5 disassembly that opens paracellular gaps in the intestinal epithelium. Net effect: reduces intestinal permeability, decreases gluten-derived peptide and LPS translocation into the lamina propria, and dampens downstream cytokine activation. Acts locally in the gut lumen: minimal systemic absorption (<1%). Phase 2b at 0.5 mg TID reduced celiac symptoms vs placebo; phase 3 (CeDLara) failed to meet primary endpoint.

Dosing

Any amounts shown here are reported from published studies only. 3 of 3 catalogued studies involved human subjects. COMPOUND does not publish its own dosing guidance.

Where a study reports an amount, it appears in that study's entry below, attributed to the source.

Published evidence

  1. Human RCT 2022

    CeDLara Phase 3 trial discontinued for futility

    9 Meters Biopharma (corporate announcement, NCT04835571) Press release / SEC 8-K filing

    Pivotal phase 3 in 525 celiac patients failed to meet its primary endpoint at interim analysis. Trial discontinued June 2022. No follow-on commercial development.

  2. Human RCT 2015

    Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial

    Leffler DA, Kelly CP, Green PHR, Fedorak RN, DiMarino A, Perrow W, Rasmussen H, Wang C, Bercik P, Bachir NM, Murray JA Gastroenterology

    Phase 2b in 342 celiac patients on GFD with persistent symptoms. Larazotide 0.5 mg TID reduced CeD-PRO symptom score significantly vs placebo. Established the 0.5 mg pre-meal dose pattern. Best published efficacy data, though phase 3 later failed to replicate.

    PMID 25448925

  3. Human RCT 2007

    The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects

    Paterson BM, Lammers KM, Arrieta MC, Fasano A, Meddings JB Aliment Pharmacol Ther

    First human trial of larazotide. Established negligible systemic absorption, safety profile, and reduction in intestinal permeability after gluten challenge.

    PMID 17697209

Reported side effects

Headache
Occasional Mild · Most common side effect in CeDLara phase 2/3 trials. Usually mild and self-limiting.
Urinary tract infection
Occasional Mild · Reported imbalance in trial. Mechanism unclear, may be incidental.
Upper respiratory infection
Occasional Mild · Trial-reported imbalance, possibly placebo-comparable.
Flatulence / GI changes
Occasional Mild · Mild, transient.

Storage

Cool dry place, original packaging, protect from moisture. Shelf-life 2 years.