Safety Study of Larazotide Acetate to Treat Celiac Disease.

Overview

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.

Full Title of Study: “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.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: January 26, 2006

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.

Interventions

  • Drug: larazotide acetate
    • larazotide acetate 4 mg capsules

Arms, Groups and Cohorts

  • Experimental: Larazotide acetate
    • Larazotide acetate capsules: 12 mg QD x 3 days
  • Placebo Comparator: Placebo
    • Placebo capsules: QD x 3 days

Clinical Trial Outcome Measures

Primary Measures

  • Demonstrate the safety and tolerance of single doses of larazotide acetate in patients with controlled celiac disease on a gluten-free diet.
    • Time Frame: 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.
    • 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).
  • 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
    • Time Frame: erial blood samples were collected for pharmacokinetic determinations at baseline and 2 and 3 hours post dose.
    • 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.
  • Evaluate the effects of single doses of larazotide acetate on intestinal permeability ratios and zonulin levels
    • Time Frame: Intestinal permeability was measured each day following dosing. A gluten challenge was administered on Day 2.
    • 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.

Secondary Measures

  • Self-reported measures of GI discomfort
    • Time Frame: Once daily on dosing days
    • 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.
  • Patient Global Assessment of Disease Status
    • Time Frame: At discharge from the clinic
    • 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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 59 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • 9 Meters Biopharma, Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Blake Paterson, MD, Study Chair, Alba Therapeutics

Citations Reporting on Results

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.

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