Safety Study of Larazotide Acetate to Treat Celiac Disease.

Study Overview
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Brief Summary
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To demonstrate the safety, pharmacokinetics and efficacy of larazotide acetate in patients with controlled celiac disease on a gluten-free diet following a gluten challenge.

Detailed Description
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CLIN1001-002 was a Phase 1b, randomized, double-blind, placebo controlled study to determine the safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of larazotide acetate in subjects with celiac disease subjects. Study subjects were randomized (2:1) to receive single oral doses of larazotide acetate 12 mg or matching placebo once daily for 3 days. Subjects received a single-blinded gluten challenge (5 mg amygluten) on Day 2. Intestinal permeability was measured each day following dosing. Intestinal permeability was measured by administration of an oral sucrose, lactulose and mannitol solution followed by a 6-hour urine collection. Serial blood samples were collected for pharmacokinetic determinations at baseline and 2 and 3 hours post dose; for zonulin determinations at baseline (prior to first dose) and 3 hours post dose; and for cytokine determination at baseline and 3 hours post dose (Days 2 and 3 only) and on Day 7. Sucrose, lactulose, mannitol, zonulin and larazotide acetate concentrations were determined by validated analytical methods.

Official Title
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A Phase Ib, Randomized, Double-Blind, Placebo Controlled Study to Determine the Safety, Tolerance, Pharmacokinetic and Pharmacodynamic Effects of Single Doses of Larazotide Acetate (AT-1001) in Celiac Disease Subjects.

Conditions
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Celiac Disease

Intervention / Treatment
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* Drug: larazotide acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must have been diagnosed with celiac disease by biopsy for ≥ 6 months (attending physician confirmation will be accepted in lieu of a biopsy report). Subject must be on a gluten-free diet for at least the past 6 months. Exclusion Criteria: Subject has Anti-Tissue Transglutaminase (tTG) > 10 EU as measured by serology Subject intermittently consumes clinically significant quantities of non-steroidal anti-inflammatory agents (NSAIDs) and proton-pump inhibitors, within the last 3 days prior to the treatment visit.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Larazotide acetate<br>Larazotide acetate capsules: 12 mg QD x 3 days | Drug: larazotide acetate<br>* larazotide acetate 4 mg capsules<br>* Other names: INN-202;|
| Placebo Comparator: Placebo<br>Placebo capsules: QD x 3 days | Drug: larazotide acetate<br>* larazotide acetate 4 mg capsules<br>* Other names: INN-202;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demonstrate the safety and tolerance of single doses of larazotide acetate in patients with controlled celiac disease on a gluten-free diet. | Safety assessments included scheduled monitoring of adverse events (AEs), vital sign measurements, 12-lead ECG measurements, physical examinations, and clinical laboratory testing (chemistry, hematology, and urinalysis). | AEs were monitored throughout the study. Clinical laboratory testing was performed at scheduled times throughout the study. ECGs were measured at baseline, 3 hours post-dose on all study days and at the follow-up visit. | 
| Determine whether quantifiable concentrations of larazotide acetate are present in plasma following single oral doses and to characterize the pharmacokinetic behavior of larazotide acetate in celiac disease subjects that are gluten-free and in remission | Pharmacokinetic samples were taken to determine whether quantifiable concentrations of larazotide acetate were present in plasma following single oral doses and to characterize the pharmacokinetic behavior of larazotide acetate in celiac disease subjects. | erial blood samples were collected for pharmacokinetic determinations at baseline and 2 and 3 hours post dose. | 
| Evaluate the effects of single doses of larazotide acetate on intestinal permeability ratios and zonulin levels | Intestinal permeability was measured by administration of an oral sucrose, lactulose and mannitol solution followed by urine and serum collection to measure urinary lactulose and mannitol, and serum zonulin concentrations as biomarkers. | Intestinal permeability was measured each day following dosing. A gluten challenge was administered on Day 2. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-reported measures of GI discomfort | GI discomfort was reported by marking an X on a 10 cm linear line. Other GI Symptoms were assessed by subjects answering three questions related to bowel function. | Once daily on dosing days | 
| Patient Global Assessment of Disease Status | Subjects chose one of seven ordinal levels in response to a question related to any change in their disease status since being admitted to the clinic | At discharge from the clinic | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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larazotide acetate