Safety Study of AT1001 to Treat Celiac Disease.
To demonstrate the safety and tolerance of single, oral doses of AT-1001 in celiac disease subjects that are gluten-free diets and in remission.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Primary Purpose: Treatment
|Official Title:||A Phase Ib, Randomized, Double-Blind, Placebo Controlled Study to Determine the Safety, Tolerance, Pharmacokinetic and Pharmacodynamic Effects of Single Doses of AT-1001 in Celiac Disease Subjects.|
- To demonstrate the safety and tolerance of single, oral doses of AT-1001 in celiac disease subjects that are gluten-free and in remission
- To determine whether quantifiable AT-1001 concentrations are present in plasma following single oral doses and to characterize the pharmacokinetic behavior of AT-1001 in celiac disease subjects that are gluten-free and in remission
- To evaluate the effects of single doses of AT-1001 on intestinal permeability ratios and zonulin levels following single, oral challenge doses of gluten (2.5 gm) by utilizing urinary lactulose and mannitol, and serum zonulin concentrations as biomarkers.
- Self-reported measures of GI discomfort
- Pharmacokinetic Measures
- Pharmacodynamic Measures
|Study Start Date:||January 2006|
|Estimated Study Completion Date:||February 2006|
One (1) cohort of 24 (2:1 drug:placebo) subjects will receive single oral doses of either AT-1001 or matching placebo. Subjects will complete screening and thereafter be admitted to the clinic prior to treatment. On Day 1 AT-1001 or matching placebo will be administered followed by a baseline intestinal permeability test. Intestinal permeability will be measured by administration of an oral sucrose, lactulose and mannitol solution followed by an 8-hour urine collection. Day 2 subjects will be given AT-1001 or matching placebo followed by a gluten challenge and have the intestinal permeability test repeated. Day 3 subjects will be administered AT-1001 or matching placebo followed by a post gluten challenge intestinal permeability test. Serial blood samples will be collected for pharmacokinetic determinations at baseline, 2, and 3 hours post administration of AT-1001 or matching placebo, for zonulin determinations at baseline (prior to first dose) and at 3 hours post dose, and for cytokine determination at baseline, 3 hours post dose (Days 2 and 3 only) and Day 7. Sucrose, lactulose, mannitol, zonulin and AT-1001 concentrations will be determined by validated analytical methods.
Subjects will be evaluated at screening (medical history, physical examination, vital signs, clinical laboratory testing, and 12-lead electrocardiogram). Vital signs and clinical laboratory testing will be conducted pre-dose and vital signs, clinical laboratory testing and EKG will be monitored post dose. Adverse event reports will be monitored throughout the study. At the end of the study a physical exam and clinical laboratory testing will be performed.