Safety Study of Larazotide Acetate to Treat Celiac Disease.

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.

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.

Study Overview

• Status: Completed
• Conditions: Celiac Disease
• Intervention / Treatment: Drug: larazotide acetate

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Parexel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Larazotide acetate; Larazotide acetate capsules: 12 mg QD x 3 days	Drug: larazotide acetate; larazotide acetate 4 mg capsules; Other Names: AT-1001; INN-202
Placebo Comparator: Placebo; Placebo capsules: QD x 3 days	Drug: larazotide acetate; larazotide acetate 4 mg capsules; Other Names: AT-1001; INN-202

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: 9 Meters Biopharma, Inc.
• Investigators: Study Chair: Blake Paterson, MD, Alba Therapeutics

Publications and helpful links

General Publications

• 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 Sep 1;26(5):757-66. doi: 10.1111/j.1365-2036.2007.03413.x.

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2005
• Primary Completion (Actual): January 26, 2006
• Study Completion (Actual): January 26, 2006

Study Registration Dates

• First Submitted: October 9, 2006
• First Submitted That Met QC Criteria: October 10, 2006
• First Posted (Estimate): October 11, 2006

Study Record Updates

• Last Update Posted (Actual): September 11, 2017
• Last Update Submitted That Met QC Criteria: September 8, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: larazotide acetate
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Celiac Disease
• Other Study ID Numbers: CLIN1001-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No