Safety and Tolerability Study of Larazotide Acetate in Celiac Disease Subjects

Celiac Disease Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00362856
• Other study ID #: CLIN1001-004
• Status: Completed
• Phase: Phase 2
• First received: August 8, 2006
• Last updated: September 11, 2017
• Start date: September 13, 2006
• Est. completion date: March 6, 2007

Study information

• Verified date: September 2017
• Source: Innovate Biopharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: March 6, 2007
• Est. primary completion date: March 6, 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Celiac Disease

Intervention

Drug:
• larazotide acetate
capsule
• Placebo
capsule

Locations

Country	Name	City	State
United States	Research Site	Boston	Massachusetts
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Richmond	Virginia
United States	Research Site	Rochester	Minnesota
United States	Research Site	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Innovate Biopharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (1)

Leffler DA, Kelly CP, Abdallah HZ, Colatrella AM, Harris LA, Leon F, Arterburn LA, Paterson BM, Lan ZH, Murray JA. A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge. Am J Gastroenter — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To demonstrate the safety and tolerability of multiple, oral doses of larazotide acetate in celiac disease subjects that maintain a gluten-free diet.	Safety endpoints assessed in this study were adverse events, vital signs, hematology, clinical chemistry, urinalysis and ECG	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).
Primary	To evaluate the efficacy of multiple dose levels of larazotide acetate in preventing intestinal permeability changes induced by gluten challenge	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	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.
Secondary	Changes in daily and weekly reported health outcomes	Health outcomes were assessed using a daily symptom diary; a weekly PGWBI and a weekly GSRS	Symptom diary - daily; PGWBI - weekly; GSRS - weekly
Secondary	Changes in urinary LAMA ratios between Day 0 to Day 7	See Primary Outcome Measure No. 2	See Primary Outcome Measure No. 2
Secondary	Changes in urinary lactulose fractional excretion between Day 0 to Day 7 to Day 14	See Primary Outcome Measure No. 2	See Primary Outcome Measure No. 2
Secondary	Changes in urinary mannitol fractional excretion between Day 0 to Day 7 to Day 14	See Primary Outcome Measure No. 2	See Primary Outcome Measure No. 2
Secondary	Change in urinary nitrite / nitrate levels from Day 0 to Day 14	Nitrite/nitrate levels were assessed for correlation to the measures of intestinal permeability	Day 0 and Day 14
Secondary	Change in anti-tTG levels from Screening to Day 21	Changes between screening and Day 21 anti-tTG levels were assessed for correlation to the measures of intestinal permeability	Screening and Day 21
Secondary	Change in cell markers and cytokines from PBMCs	Serum cytokine and cell surface marker determinations were assessed for correlation to the measures of intestinal permeability	Days 0, 7, 14 and 21
Secondary	Changes in zonulin level	Serum zonulin levels were assessed for correlation to the measures of intestinal permeability	Days 0, 7, 14 and 21