MEDICAL DISCLAIMER: Educational research guidelines only. Lyophilized peptides are investigational chemical compounds and are NOT approved for human consumption, diagnosis, or therapy. Consult a licensed physician before any research application.
Larazotide acetate Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
Larazotide acetate (AT-1001, INN-202) is a first-in-class tight-junction regulator, or zonulin antagonist, studied as an adjunct for celiac disease (PMID 25683116). It is a synthetic octapeptide that acts locally at the small-intestinal surface to keep tight junctions closed, reducing the leak of gluten peptides across the gut barrier; it inhibits zonulin signaling and myosin light chain kinase to help reassemble tight-junction proteins (PMID 33881350). It is minimally absorbed, so it is taken orally before meals rather than relying on systemic exposure. The only effective dose in Phase 2b was 0.5 mg three times daily; higher 1 mg and 2 mg doses were no better than placebo. The subcutaneous reconstitution scheme here is an educational measurement reference only. Larazotide acetate is not FDA- or EMA-approved; its Phase 3 trial was discontinued for futility in June 2022, and it is sold for research use only.
Reconstitute: Add 2 mL bacteriostatic water → 5 mg/mL concentration.
Typical dose: 0.5 mg before each meal (3x/day), oral
Easy measuring: At 5 mg/mL, 1 unit = 0.01 mL = 0.0500 mg (50 mcg) on a U-100 insulin syringe.
Storage: Lyophilized powder stored frozen at −20 °C, protected from light and moisture. Reconstituted solution kept refrigerated at 2-8 °C and used within ~2-4 weeks. Clinical delayed-release capsules are stored at controlled room temperature.
Half-life: No conventional systemic half-life — larazotide is gut-restricted and minimally absorbed; peak luminal levels in the duodenum/proximal jejunum ~1 h after an oral dose, with a local, meal-timed effect.
Route: Oral delayed-release capsule taken before each meal (3x/day); modeled here as a subcutaneous reconstitution reference for unit measurement only.
Status: Not FDA- or EMA-approved; investigational, Phase 3 discontinued for futility (June 2022); research/educational use only, not medical advice.
About Larazotide acetate
Larazotide acetate (AT-1001, INN-202) is an investigational tight-junction regulator studied for celiac disease. It is a synthetic octapeptide that acts as a zonulin antagonist, working locally on the inner lining of the small intestine to keep the paracellular tight junctions closed so that gluten fragments are less able to cross the gut barrier [1][4]. Clinically, and in every published human trial, larazotide acetate is taken ORALLY as a delayed-release capsule before meals — it is essentially not absorbed into the bloodstream, so the subcutaneous reconstitution figures below are an educational measurement reference only, not the real-world route.\n\nThe established Larazotide acetate dosage is small and fixed rather than titrated: the Phase 2b trial found that 0.5 mg three times daily before meals was the only dose to beat placebo, while 1 mg and 2 mg three times daily were no better than placebo — an unusual inverted dose-response [1]. Other trials explored 1, 4, and 8 mg three times daily during gluten challenge [2][3].\n\nThis guide models a 10 mg vial reconstituted with 2.0 mL of bacteriostatic water (5 mg/mL) so the doses land on clean, measurable marks on a U-100 insulin syringe: 0.5 mg = 10 units, 1 mg = 20 units, and 2 mg = 40 units. Because larazotide is dosed in milligrams and acts at the gut surface, these injection figures are purely a unit-conversion teaching aid.\n\nFrequency: Three times daily, taken just before each main meal so the peptide is present in the gut lumen when dietary gluten arrives. Larazotide acetate is not FDA- or EMA-approved and is presented here for educational purposes only.
Quick Protocol Navigation
Reconstitution Instruction & Mixing Step-by-Step
Lyophilized powder must be reconstituted carefully. Agitating peptide chains can shear disulfide bonds and render the peptide biologically inert.
Draw 2.0 mL of bacteriostatic water into a sterile syringe (this yields a 5 mg/mL solution from a 10 mg vial, i.e. 50 mcg per insulin-syringe unit).
Inject the water slowly down the inner wall of the 10 mg larazotide acetate vial; do not aim the stream at the powder, and avoid vigorous shaking.
Gently swirl or roll the vial until the solution is completely clear; the result is 5 mg/mL (5000 mcg/mL).
Store refrigerated at 2-8 °C; for the educational model, draw the units for your dose (0.5 mg = 10 units, 1 mg = 20 units, 2 mg = 40 units on a U-100 syringe).
Educational note: larazotide acetate is clinically taken ORALLY as a delayed-release capsule before each meal and is not meaningfully absorbed — these subcutaneous reconstitution figures are a unit-measurement reference only, not a validated delivery route.
Interactive Larazotide acetate Syringe Calculator
Currently visualizing the 10 mg vial reconstituted with 2 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 10mg dry powder in 2mL water yields 5.00 mg/mL. To evaluate a 250mcg dose, pull to 5.0 units (5 syringe ticks).
U-100 Syringe Representation
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Phase | Dose per injection | Units (per injection) |
|---|---|---|
| Phase 2b effective dose — 0.5 mg before each meal (3x/day) | 500 mcg | 10 units (0.10 mL) |
| Higher arm tested — 1 mg before each meal (no better than placebo) | 1000 mcg (1 mg) | 20 units (0.20 mL) |
| Higher arm tested — 2 mg before each meal (no better than placebo) | 2000 mcg (2 mg) | 40 units (0.40 mL) |
Administration guidelines: Refer to guidelines | 2 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 10 mg vial.
Peptide Vials (Larazotide acetate, 10 mg each):
- check8 weeks at 0.5 mg 3x/day (1.5 mg/day) ≈ 9 vials (84 mg total)
- check12 weeks at 0.5 mg 3x/day ≈ 13 vials (126 mg total)
- check16 weeks at 0.5 mg 3x/day ≈ 17 vials (168 mg total) — in practice larazotide is dosed as oral capsules, not vials
Insulin Syringes (U-100):
- checkThree doses per day = 21 syringes per week
- check8 weeks ≈ 168 syringes; 12 weeks ≈ 252 syringes
- check16 weeks ≈ 336 syringes (each 0.5 mg dose ≈ 10 units)
Bacteriostatic Water (30 mL bottles): Use 2 mL per 10 mg vial for reconstitution.
- check8 weeks (≈9 vials) ≈ 18 mL ≈ 1 bottle
- check12 weeks (≈13 vials) ≈ 26 mL ≈ 1 bottle
- check16 weeks (≈17 vials) ≈ 34 mL ≈ 2 bottles
Alcohol Swabs:
- check1-2 swabs per dose (vial top + injection site), 3 doses/day
- check8 weeks ≈ 170-340 swabs; 12 weeks ≈ 250-500 swabs
- check16 weeks ≈ 340-670 swabs; keep extras for re-swabbing multi-use vials
Mechanism of Action (MOA)
Larazotide acetate is a synthetic single-chain octapeptide (Gly-Gly-Val-Leu-Val-Gln-Pro-Gly) originally derived from the zonula occludens toxin (Zot) of Vibrio cholerae and engineered to resist gastric acid and proteolytic degradation so it reaches the small intestine intact [4]. It is the first-in-class \"tight-junction regulator,\" frequently described as a zonulin antagonist. Zonulin is the endogenous human analogue of Zot, and when it is released in response to gliadin and other triggers it loosens the protein gates (the tight junctions) that seal the spaces between intestinal epithelial cells. In celiac disease this paracellular leak allows immunogenic gluten peptides to reach the lamina propria and drive the autoimmune cascade [1][4].\n\nMechanistically, larazotide works at the apical (luminal) surface of enterocytes. It is proposed to competitively block zonulin from engaging its target receptors — implicated to include EGFR and PAR2 — thereby preventing the downstream activation of myosin light chain kinase (MLCK). Because MLCK-driven cytoskeletal contraction is what physically pulls tight-junction proteins apart, inhibiting this step reduces tension on the actin filaments and promotes the redistribution and reassembly of tight-junction proteins (such as ZO-1 and occludin), restoring barrier integrity [4]. The net effect is a gut barrier that is more resistant to gliadin-induced opening, lowering antigen flux rather than acting on the immune system directly.\n\nPharmacokinetics are unusual and central to how it is dosed. Larazotide acetate is a locally acting, gut-restricted drug: it is minimally absorbed into the systemic circulation, so it has no clinically meaningful plasma concentration or systemic elimination half-life in the conventional sense [4]. In animal studies of delayed-release oral formulations, peak luminal concentrations were found in the duodenum and proximal jejunum about one hour after dosing, matching the site where gluten exposure and barrier disruption occur [4]. Because its protective effect is local and transient and must coincide with the arrival of dietary gluten, the drug is taken three times daily immediately before meals; this meal-timed dosing — not a long half-life — is what sustains the effect through the day.\n\nThe clinical dose-response is famously non-linear. In the Phase 2b trial, 0.5 mg three times daily significantly reduced symptoms versus placebo, whereas 1 mg and 2 mg three times daily were indistinguishable from placebo, an inverted U-shaped curve thought to reflect peptide self-aggregation or receptor-level effects at higher luminal concentrations [1]. Downstream, the intended consequence is fewer gluten-triggered symptoms (abdominal pain, bloating, and even non-GI symptoms such as headache and fatigue) in patients who still react despite a gluten-free diet [1].\n\nThe real-world route is oral; the subcutaneous reconstitution scheme on this page is an educational measurement convention used across this site, not a clinically validated delivery method. Larazotide acetate is not approved by any major regulator: its Phase 3 program was discontinued for futility in June 2022, and it remains restricted to research and educational use [6][7].
Clinical Trial Efficacy Highlights
- starPaterson and colleagues (2007, Aliment Pharmacol Ther) ran the first proof-of-concept human study of AT-1001, giving single oral doses to celiac subjects undergoing an acute gluten challenge and using the lactulose-to-mannitol intestinal permeability ratio as an exploratory marker; the peptide was safe and well tolerated and signaled a reduction in gluten-induced intestinal barrier dysfunction, establishing the rationale for tight-junction regulation as a therapeutic target [4].
- starLeffler and colleagues (2012, American Journal of Gastroenterology) randomized 86 celiac patients in a double-blind study of larazotide acetate to prevent activation of celiac disease during a gluten challenge; larazotide limited gluten-induced increases in intestinal permeability and reduced symptom and antibody responses relative to placebo, supporting a barrier-protective mechanism [3].
- starKelly and colleagues (2013, Aliment Pharmacol Ther) studied 184 gluten-free patients randomized to larazotide acetate 1, 4, or 8 mg three times daily versus placebo while receiving 2.7 g of gluten daily for six weeks; larazotide reduced gluten-induced immune reactivity and symptoms and was generally well tolerated, although the primary permeability (LAMA-ratio) endpoint was not met [2].
- starThe pivotal Phase 2b trial (Leffler et al., 2015, Gastroenterology) enrolled 342 adults with persistent symptoms despite a gluten-free diet and tested 0.5, 1, and 2 mg three times daily; only the 0.5 mg dose met the primary endpoint, significantly improving the celiac GI symptom rating scale versus placebo (P = .022), with a 26% decrease in symptomatic days and a 31% increase in improved-symptom days [1].
- starThe same Phase 2b trial demonstrated an inverted dose-response: the 1 mg and 2 mg three-times-daily arms were no different from placebo on any endpoint, an important and unusual finding indicating that more drug was not better and that 0.5 mg before meals is the dose carried forward [1].
- starAcross the development program, larazotide also reduced non-gastrointestinal complaints such as headache and tiredness in symptomatic celiac patients, suggesting that limiting gluten-triggered barrier opening can address systemic as well as luminal symptoms [1].
- starA review of the pharmacology (Slifer et al., 2021, Am J Physiol Gastrointest Liver Physiol) synthesized evidence that larazotide stabilizes tight junctions by antagonizing zonulin signaling and inhibiting myosin light chain kinase, restoring redistribution of tight-junction proteins, and confirmed that the peptide acts locally in the gut with negligible systemic absorption [4].
- starDespite this body of positive Phase 2 signals, the Phase 3 CeDLara trial (sponsored by 9 Meters Biopharma) was discontinued in June 2022 after an interim futility analysis concluded that an impractically large number of additional patients would be required to show a statistically significant benefit, leaving efficacy unconfirmed in a confirmatory trial [6][7].
Side Effects & Tolerability Profile
Clinical subjects transiently report mild side effects. Slowly escalating the titration dose represents the single most effective intervention to limit side effects.
- warningLarazotide acetate has a notably favorable tolerability profile across more than 15 years of trials; single and multiple oral doses from roughly 0.25 mg up to 36 mg were generally well tolerated with no serious drug-related adverse events reported in early studies [1][4].
- warningHeadache was the most commonly reported adverse event in clinical studies, but its frequency did not differ meaningfully between larazotide and placebo groups, making it difficult to attribute directly to the drug [1].
- warningGastrointestinal symptoms (abdominal pain, bloating, diarrhea, nausea, flatulence) were reported, but in celiac patients these are often indistinguishable from the underlying disease and from gluten exposure rather than the peptide itself [1][2].
- warningNo clinically significant hepatic, renal, or bone toxicity was observed in the trial program, consistent with the drug's minimal systemic absorption and gut-restricted action [4].
- warningBecause larazotide acts locally and is essentially not absorbed, systemic and off-target effects are expected to be low; however, it is not a substitute for a gluten-free diet and does not treat the underlying autoimmunity of celiac disease [1][4].
- warningThe dose-response is counter-intuitive: higher doses (1-2 mg three times daily) were not more effective and showed no added benefit over placebo, so escalating the dose is not supported and may be pointless [1].
- warningLong-term safety beyond the trial durations is not fully characterized, and the confirmatory Phase 3 trial was stopped early for futility rather than for safety, so definitive long-term human data are lacking [6][7].
- warningRegulatory/research status: larazotide acetate is NOT approved by the FDA or EMA for any indication; it is an investigational compound whose Phase 3 program was discontinued in 2022, and it is sold only for research. This page is educational and is not medical advice [6][7].
Subcutaneous Injection Technique
Most research peptides require subcutaneous injection into fatty tissue. Never inject directly into a blood vessel or deep muscle tissue unless clinically detailed.
1. Site Selection
Common locations include the abdomen (2 inches from navel), outer upper arms, or thighs.
2. Sanitization
Thoroughly clean the selected site, stopper and vial top using 70% isopropyl alcohol prep swabs.
3. Angle & Push
Pinch the skin and insert the needle at a 45 to 90-degree angle. Depress plunger smoothly.
4. Site Rotation
Rotate injection sites continuously to avoid lipodystrophy or tissue scarring.
Frequently Asked Questions
What is the typical Larazotide acetate dosage?expand_more
In the pivotal Phase 2b trial the effective Larazotide acetate dosage was 0.5 mg taken orally three times daily, just before each main meal. Notably, this was the only dose that beat placebo: the higher 1 mg and 2 mg three-times-daily arms were no better than placebo, an inverted dose-response. Other trials explored 1, 4, and 8 mg three times daily during gluten challenge, but 0.5 mg before meals is the figure carried into Phase 3. It is dosed in milligrams as an oral delayed-release capsule; the subcutaneous unit figures on this page are an educational measurement reference only.
Is Larazotide acetate FDA approved?expand_more
No. Larazotide acetate (AT-1001, INN-202) is not approved by the FDA or the EMA for any indication. It was the most advanced investigational celiac disease drug and the first to reach Phase 3, but the confirmatory Phase 3 CeDLara trial (sponsored by 9 Meters Biopharma) was discontinued for futility in June 2022 after an interim analysis. It remains an investigational, research-use-only compound, and this page is educational and not medical advice.
What is the half-life of Larazotide acetate?expand_more
Larazotide acetate does not have a conventional systemic half-life because it is a locally acting, gut-restricted peptide that is minimally absorbed into the bloodstream. It acts at the surface of the small-intestinal lining, with peak luminal concentrations in the duodenum and proximal jejunum about one hour after an oral dose in animal studies. Its protective effect is local and transient, which is why it is taken three times daily before meals rather than relying on a long plasma half-life.
How is Larazotide acetate reconstituted and administered?expand_more
Clinically, larazotide acetate is swallowed as a delayed-release capsule before meals, so no reconstitution is needed in real-world use. For the educational subcutaneous model on this site, a 10 mg vial is mixed with 2.0 mL of bacteriostatic water to give 5 mg/mL (50 mcg per unit): draw the water slowly down the vial wall, swirl gently until clear, and refrigerate. At that concentration 0.5 mg measures 10 units, 1 mg measures 20 units, and 2 mg measures 40 units on a U-100 insulin syringe. These injection figures are a unit-conversion teaching aid only.
Can Larazotide acetate be stacked with other gut compounds?expand_more
There is no validated stacking protocol. In research settings larazotide is sometimes discussed alongside other gut-barrier or anti-inflammatory peptides (such as BPC-157 or KPV), but no controlled human data support these combinations, and larazotide itself failed to confirm efficacy in Phase 3. Importantly, larazotide is an adjunct studied alongside a gluten-free diet, not a replacement for it. Treat any combination as experimental; this content is educational only and not medical advice.
Related Guides & Tools
Step-by-step references for reconstituting, measuring, and storing Larazotide acetate, plus the universal dosing calculator.
Academic References & Study Citations
Leffler DA, Kelly CP, Green PHR, et al. Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial. Gastroenterology. 2015;148(7):1311-9.e6. View Scientific Paper →
Kelly CP, Green PHR, 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. View Scientific Paper →
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. View Scientific Paper →
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. View Scientific Paper →
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. View Scientific Paper →
Celiac Disease Foundation. 9 Meters Discontinues Phase 3 Clinical Trial for Potential Celiac Disease Drug Larazotide. June 21, 2022. View Scientific Paper →
ClinicalTrials.gov. NCT03569007 — Study to Evaluate the Efficacy and Safety of Larazotide Acetate for the Relief of CeD Symptoms (CeDLara), Phase 3. View Scientific Paper →