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.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Demonstrate the safety and tolerance of single doses of larazotide acetate in patients with controlled celiac disease on a gluten-free diet.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Larazotide acetate
Larazotide acetate capsules: 12 mg QD x 3 days
干预措施: larazotide acetate (Drug)
Placebo
Placebo capsules: QD x 3 days
干预措施: larazotide acetate (Drug)
结局指标
主要结局
Demonstrate the safety and tolerance of single doses of larazotide acetate in patients with controlled celiac disease on a gluten-free diet.
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Patient Global Assessment of Disease Status(At discharge from the clinic)
- Self-reported measures of GI discomfort(Once daily on dosing days)