A Double Blind, Randomized, Placebo Controlled, Parallel Group Study to Investigate the Effect of ATI-7505 on Gastric Emptying and Small Bowel and Colonic Transit in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Ascending colonic emptying t1/2
研究概览
简要总结
This is a pharmacodynamic study in healthy volunteers to determine the effects of a new 5-HT4 agonist on gastric, small bowel and colonic transit.
详细描述
ATI-7505, is an engineered analog of the 5-HT4 agent, cisapride. The objectives of this study are to compare effects of ATI-7505 and placebo on gastric, small bowel and colonic transit in healthy human volunteers and evaluate the safety and tolerability of ATI-7505.
This trial is a double-blind, randomized, placebo-controlled study evaluating the gastrointestinal transit effects of ATI-7505 and placebo. Three different doses (3, 10, 30mg) of ATI-7505 and placebo will be administered in parallel to four independent groups of 12 subjects each. The maximum duration of drug exposure for any subject is 9 days.
All participants will undergo a standard 48 hour gastrointestinal transit measurement using scintigraphy with standardized meals during the first 12 hours. The response endpoints (colonic geometric center at 4 h, colonic geometric center at 24 h, colonic geometric center at 48 h, gastric residual at 2 & 4 h, colonic filling at 6 h and ascending colonic emptying t1/2) will be based on abdominal scintigraphic images following the technetium-99m egg meal and methacrylate-coated, delayed-release capsule containing 111In labeled activated charcoal.
Safety and tolerability will be evaluated by serial assessment of vital signs, physical examination, ECG, adverse events, concomitant medications and blood sample analysis.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteers between the ages of 18 to 65 years old (inclusive) with a BMI ≥ 18 and ≤ 32
- •PR, QRS and QT intervals within normal limits on screening ECG. Specifically, PR < 220 msec, QRS < 140 msec, QTc < 450 msec
- •Are able and willing to understand study requirements, follow instructions, attend all required study visits (especially during 48 hrs of scintigraphic scan), undergo all planned tests (including drawing of blood samples and consumption of standardized study meals)
- •Are able and willing to sign IRB-approved, written informed consent to participate in this study
- •Have had negative urine screen and clinical history (prior 2 years) for drugs of abuse at screening visit
- •Women with no child bearing potential, as defined by at least 1 year post-menopausal (absence of vaginal bleeding or spotting) or surgically sterile. Men will have a sterile sexual partner or will, starting at time of study drug administration a minimum of 1 month after study drug administration, be willing to use an approved method of contraception (which may include use of a condom with spermicide or use by partner of oral, implantable or injectable contraceptives, IUD, diaphragm with spermicide)
- •Exclusion Criteria
- •Inability to understand study requirements or follow study procedures (especially entire 48 h of scintigraphy examination), attend all required study visits, undergo all planned tests (including drawing of blood samples and consumption of study meals)
- •Any out of range laboratory value at screening that has not been reviewed, approved and documented as not clinically significant (NCS) by the Principal Investigator.
- •Use of alcohol within 24 h of randomization visit (Visit 2) and through completion of the study
- •History of untoward effects of metoclopramide
- •Any clinically significant abnormality on screening ECG.
- •Any other condition or clinically significant abnormal findings on the physical examination, medical history, or clinical laboratory results during screening that, in the opinion of the Principal Investigator, would make the subject unsuitable for the study or put them at additional risk)
- •Known allergy, hypersensitivity or sensitivity to cisapride
- •Pregnancy or lactation
- •History of alcohol or other substance abuse within the past two years
- •Received treatment with any other investigational drug within the preceding 30 days or 5 half-lives, whichever is greater
- •Major surgery within 3 months of study entry and any surgery within 2 weeks of study entry unless approved by the Principal Investigator and Sponsor?s Medical Monitor
- •Any documented history of irregular intestinal transit including but not limited to gastro-esophageal reflux disease (GERD), gastroparesis of any kind, irritable bowel syndrome, inflammatory bowel disease and chronic constipation or diarrhea under the care of a physician and/or requiring daily medication
- •Any history of gastrointestinal tract or abdominal surgery, except tubal ligation, hysterectomy, appendectomy, cholecystectomy or hemorrhoid surgery > 3 months prior to screening
- •More than three positive (i.e., ?yes?) responses on screening bowel symptom questionnaire
排除标准
- 未提供
研究组 & 干预措施
3 mg ATI-7505
3 mg ATI-7505 three times daily for 9 days followed by transit scintigraphy
干预措施: ATI-7505 (Drug)
Placebo
Placebo capsule three times daily for 9 days followed by transit scintigraphy
干预措施: Placebo (Drug)
10 mg ATI-7505
10 mg ATI-7505 three times daily for 9 days followed by transit scintigraphy
干预措施: ATI-7505 (Drug)
20 mg ATI-7505
20 mg ATI-7505 three times daily for 9 days followed by transit scintigraphy
干预措施: ATI-7505 (Drug)
结局指标
主要结局
Ascending colonic emptying t1/2
时间窗: 24 hours
As measured with scintigraphic method following 111In labeled capsule and 99Tc labeled egg breakfast
Colonic geometric center at 24 h
时间窗: 24 hours
Colonic geometric center determined 24 hours post first camera image following ingestion of study medication with Indium-111 capsule and breakfast with Technetium-99 labeled egg breakfast
Gastric emptying of solids (T1/2)
时间窗: 4 hours
As measured with scintigraphic method following technetium-99m egg meal
次要结局
- Colonic filling at 6 h(6 hours)
- Colonic geometric center at 48 hours(48 hours)
- Percent gastric emptying at 1, 2 and 4 hours(4 hours)