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Safety and Tolerability Study of Larazotide Acetate in Celiac Disease Subjects

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00362856
First Posted: August 10, 2006
Last Update Posted: September 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Innovate Biopharmaceuticals
  Purpose
This study was run to determine the safety, tolerance, and efficacy of multiple doses of larazotide acetate in subjects with celiac disease following a gluten challenge.

Condition Intervention Phase
Celiac Disease Drug: larazotide acetate Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
randomized, double-blind, placebo controlled, dose ranging, multicenter
Masking: Double (Participant, Investigator)
Masking Description:
double-blind
Primary Purpose: Treatment
Official Title: A Phase 2a, Randomized, Double-Blind, Placebo Controlled, Dose Ranging, Multicenter Study to Determine the Safety, Tolerance, and Efficacy of Larazotide Acetate (AT-1001) in Celiac Disease Subjects During Gluten Challenge.

Resource links provided by NLM:


Further study details as provided by Innovate Biopharmaceuticals:

Primary Outcome Measures:
  • To demonstrate the safety and tolerability of multiple, oral doses of larazotide acetate in celiac disease subjects that maintain a gluten-free diet. [ Time Frame: Safety measurements were performed at Screening and at Day 0, 7, 14, and 21 ('End of Study'). Any change from baseline value was calculated at each subsequent visit until "End of Study" (Day 21). ]
    Safety endpoints assessed in this study were adverse events, vital signs, hematology, clinical chemistry, urinalysis and ECG

  • To evaluate the efficacy of multiple dose levels of larazotide acetate in preventing intestinal permeability changes induced by gluten challenge [ Time Frame: On Days 0, 6, 13, and 20 subjects drank a solution of lactulose and mannitol. Subject's urine was collected during the day on Day 0 and overnight prior to subsequent visits and analyzed for LAMA recoveries via standardized methodologies. ]
    The primary efficacy outcome was the Day 0-to-Day 14 change in urinary LAMA ratio ( a measure of intestinal permeability) as a response to gluten


Secondary Outcome Measures:
  • Changes in daily and weekly reported health outcomes [ Time Frame: Symptom diary - daily; PGWBI - weekly; GSRS - weekly ]
    Health outcomes were assessed using a daily symptom diary; a weekly PGWBI and a weekly GSRS

  • Changes in urinary LAMA ratios between Day 0 to Day 7 [ Time Frame: See Primary Outcome Measure No. 2 ]
    See Primary Outcome Measure No. 2

  • Changes in urinary lactulose fractional excretion between Day 0 to Day 7 to Day 14 [ Time Frame: See Primary Outcome Measure No. 2 ]
    See Primary Outcome Measure No. 2

  • Changes in urinary mannitol fractional excretion between Day 0 to Day 7 to Day 14 [ Time Frame: See Primary Outcome Measure No. 2 ]
    See Primary Outcome Measure No. 2

  • Change in urinary nitrite / nitrate levels from Day 0 to Day 14 [ Time Frame: Day 0 and Day 14 ]
    Nitrite/nitrate levels were assessed for correlation to the measures of intestinal permeability

  • Change in anti-tTG levels from Screening to Day 21 [ Time Frame: Screening and Day 21 ]
    Changes between screening and Day 21 anti-tTG levels were assessed for correlation to the measures of intestinal permeability

  • Change in cell markers and cytokines from PBMCs [ Time Frame: Days 0, 7, 14 and 21 ]
    Serum cytokine and cell surface marker determinations were assessed for correlation to the measures of intestinal permeability

  • Changes in zonulin level [ Time Frame: Days 0, 7, 14 and 21 ]
    Serum zonulin levels were assessed for correlation to the measures of intestinal permeability


Enrollment: 80
Actual Study Start Date: September 13, 2006
Study Completion Date: March 6, 2007
Primary Completion Date: March 6, 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo + Gluten
placebo TID + gluten 800 mg TID administered orally in capsules
Drug: Placebo
capsule
Placebo Comparator: Placebo + Gluten placebo
placebo TID + gluten placebo TID administered orally in capsules
Drug: Placebo
capsule
Larazotide acetate 8 mg + Gluten placebo
Safety Control Arm. Larazotide acetate 8 mg TID + gluten placebo TID administered orally in capsules
Drug: larazotide acetate
capsule
Other Names:
  • AT-1001
  • INN-202
Active Comparator: Larazotide acetate 0.25 mg + Gluten
Larazotide acetate 0.25 mg TID + gluten 800 mg TID administered orally in capsules
Drug: larazotide acetate
capsule
Other Names:
  • AT-1001
  • INN-202
Active Comparator: Larazotide acetate 1 mg + Gluten
Larazotide acetate 1 mg TID + gluten 800 mg TID administered orally in capsules
Drug: larazotide acetate
capsule
Other Names:
  • AT-1001
  • INN-202
Active Comparator: Larazotide acetate 4 mg + Gluten
Larazotide acetate 4 mg TID + gluten 800 mg TID administered orally in capsules
Drug: larazotide acetate
capsule
Other Names:
  • AT-1001
  • INN-202
Active Comparator: Larazotide acetate 8 mg + Gluten
Larazotide acetate 8 mg TID + gluten 800 mg TID administered orally in capsules
Drug: larazotide acetate
capsule
Other Names:
  • AT-1001
  • INN-202

Detailed Description:

CLIN1001-004 was a randomized, double-blind, placebo controlled, dose-ranging, 7-arm, multicenter study with a gluten challenge. The objects were multiple dose safety and tolerance; efficacy (intestinal permeability [change in urinary LAMA ratio] and disease signs and symptoms) following gluten challenge.

Following a 21-day screening period, subjects were randomized to one of seven treatments groups: four groups received larazotide acetate (0.25 mg, 1 mg, 4 mg or 8 mg TID) along with an 800 mg gluten challenge, one group received placebo with an 800 mg gluten challenge, a safety control arm received the highest dose of larazotide acetate (8 mg TID) and gluten placebo and the last group received drug placebo and gluten placebo. The gluten challenge was administered as capsules (800 mg TID) with each main meal for a total of 2.4 g daily. Drug or drug placebo was administered TID 15 minutes prior to each main meal. Subjects received their assigned treatments for two weeks (Day 0 through Day 14) and came to clinic for a follow-up visit one week later (Day 21). Subjects remained on their gluten-free diet for the duration of the study.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have been diagnosed with celiac disease by biopsy for ≥ 6 months.
  • Have a Anti-Tissue Transglutaminase (tTG) ≤ 10 EU as measured by serology.
  • Must be on a gluten-free diet for at least the past 6 months.

Exclusion Criteria:

  • Have any chronic active GI disease other than celiac disease (e.g., IBS, Crohn's, Colitis).
  • Have diabetes (Type 1 or Type 2).
  • Chronically consumes non-steroidal anti-inflammatory agents ("NSAIDs") or takes proton-pump inhibitors.
  • Consuming oral corticosteroids or immune suppressants.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00362856


Locations
United States, Arizona
Research Site
Scottsdale, Arizona, United States, 85259
United States, California
San Diego, California, United States, 92123
United States, Massachusetts
Research Site
Boston, Massachusetts, United States, 02215
United States, Minnesota
Research Site
Rochester, Minnesota, United States, 55905
United States, New Jersey
Morristown, New Jersey, United States, 07960
United States, North Dakota
Bismarck, North Dakota, United States, 58501
United States, Pennsylvania
Research Site
Philadelphia, Pennsylvania, United States, 19107
Pittsburgh, Pennsylvania, United States, 15241
United States, Virginia
Research Site
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Innovate Biopharmaceuticals
  More Information

Publications:
Responsible Party: Innovate Biopharmaceuticals
ClinicalTrials.gov Identifier: NCT00362856     History of Changes
Other Study ID Numbers: CLIN1001-004
First Submitted: August 8, 2006
First Posted: August 10, 2006
Last Update Posted: September 12, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Innovate Biopharmaceuticals:
larazotide acetate

Additional relevant MeSH terms:
Celiac Disease
Malabsorption Syndromes
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Metabolic Diseases