Clinical trial NCT00362856: Safety and Tolerability Study of Larazotide Acetate in Celiac Disease Subjects
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Celiac Disease
Keywords: larazotide acetate
Lead sponsor: 9 Meters Biopharma, Inc.
Sponsor class: INDUSTRY
First posted: 2006-08-10
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, double-blind, placebo controlled, dose ranging, multicenter
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: To demonstrate the safety and tolerability of multiple, oral doses of larazotide acetate in celiac disease subjects that maintain a gluten-free diet.
timeFrame: 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).
measure: To evaluate the efficacy of multiple dose levels of larazotide acetate in preventing intestinal permeability changes induced by gluten challenge
timeFrame: 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 outcomes:
measure: Changes in daily and weekly reported health outcomes
timeFrame: Symptom diary - daily; PGWBI - weekly; GSRS - weekly
measure: Changes in urinary LAMA ratios between Day 0 to Day 7
timeFrame: See Primary Outcome Measure No. 2
measure: Changes in urinary lactulose fractional excretion between Day 0 to Day 7 to Day 14
timeFrame: See Primary Outcome Measure No. 2
measure: Changes in urinary mannitol fractional excretion between Day 0 to Day 7 to Day 14
timeFrame: See Primary Outcome Measure No. 2
measure: Change in urinary nitrite / nitrate levels from Day 0 to Day 14
timeFrame: Day 0 and Day 14
measure: Change in anti-tTG levels from Screening to Day 21
timeFrame: Screening and Day 21
measure: Change in cell markers and cytokines from PBMCs
timeFrame: Days 0, 7, 14 and 21
measure: Changes in zonulin level
timeFrame: Days 0, 7, 14 and 21
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: San Diego
country: United States
state: California
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Morristown
country: United States
state: New Jersey
city: Bismarck
country: United States
state: North Dakota
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Richmond
country: United States
facility: Research Site
state: Virginia
Study officials:
References:
citation: 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 Gastroenterol. 2012 Oct;107(10):1554-62. doi: 10.1038/ajg.2012.211. Epub 2012 Jul 24.