A Double-Blind, Placebo-Controlled, Phase 2, Responsive Adaptive Randomization Study of ORP-101 in Patients With Irritable Bowel Syndrome With Diarrhea (IBS-D)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 321
- 试验地点
- 74
- 主要终点
- Percentage of Participants Who Are Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain and Daily Stool Consistency Scores
研究概览
简要总结
This study will evaluate the effects of ORP-101 versus placebo on stool consistency and abdominal pain in patients with Irritable Bowel Syndrome with Diarrhea (IBS-D). It will also assess the safety and tolerability of ORP-101 in patients with IBS-D.
详细描述
The objectives of this study are to evaluate the efficacy, safety and tolerability of ORP-101 in patients with IBS-D. This is a randomized, double-blind, placebo-controlled, 3-arm, 12-week, parallel proof-of-concept study with 2 active arms (50 mg and 100 mg ORP-101, QD) and 1 matching placebo arm, using a responsive adaptive randomization approach. After screening, patients who qualify will enter the baseline symptom assessment period, during which they will be instructed on completion of an electronic diary for daily collection of data related to their IBS symptoms, bowel function and loperamide rescue usage (not allowed during baseline).
Patients who meet all entry criteria will be randomized to receive one of two different doses of ORP-101 tablets or placebo for 12 weeks. The study drug will be taken once daily, approximately 30 minutes prior to breakfast. Patients will return to the clinic on Days 14, 28, 56, 84 (12 weeks) and 2 weeks after dosing has completed (Day 98) for a follow-up visit.
Study subjects will include both male and female adults. Approximately 320 patients with IBS-D will be randomized to receive study drug or placebo. Randomization will be stratified by history of cholecystectomy/gallbladder agenesis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to comply with protocol, including completion of electronic daily diary as required.
- •Has a diagnosis of IBS-D (Irritable Bowel Syndrome with Diarrhea) and meets the Rome IV Criteria, by history, for both IBS and IBS-D.
- •Has abdominal pain intensity score, and stool consistency as determined by protocol and assessed by Investigator for the week prior to randomization.
- •Has not used loperamide within the 14 days prior to randomization.
- •Is on a stable diet for the past 12 weeks and is not planning to change lifestyle and/or diet during study.
排除标准
- •History of clinically relevant pancreatic conditions including pancreatitis, pancreas divisum, or Sphincter of Oddi (SO) dysfunction with pancreatic manifestations.
- •History of biliary pathology including acute cholecystitis within 6 months or biliary pain including post-cholecystectomy pain.
- •Patients who have had biliary sphincterotomy with post-procedure persistent abnormal liver function transaminases (LFTs).
- •Planned elective surgery within the next 4 months.
- •Significant and/or severe medical illnesses such as cardiovascular, neurological, infectious, renal, hepatic or respiratory disorders that would interfere with the patient's medical care, participation in, or conduct of the study.
- •History of intestinal obstruction, stricture, toxic megacolon, GI (gastro-intestinal) perforation, fecal impaction, gastric banding, bariatric surgery, adhesions, ischemic colitis, or impaired intestinal circulation (e.g. aorto-iliac disease).
- •History of lactose intolerance uncontrolled on a lactose-free diet, or other malabsorption syndromes (e.g. fructose malabsorption).
- •Dysphagia or difficulty swallowing pills.
- •History of inflammatory bowel disease, celiac disease, Clostridium difficile colitis or have had recent unexplained GI bleeding within 3 months prior to screening.
- •History of major gastric, hepatic, pancreatic or intestinal surgery (appendectomy, hemorrhoidectomy, or polypectomy allowed as long as occurred > 3 months prior to trial screening; uncomplicated laparoscopic or open cholecystectomy is allowed if no history of post-operative biliary tract pain and surgery occurred > 3 months prior to screening).
- •Patients >40 years of age at high risk for colon cancer must have had a screening colonoscopy within the past 3 years prior to trial screening visit or > 50 years of age, must have had a normal screening colonoscopy within the past 10 years prior to trial screening visit. Patients with Lynch Syndrome or Familial Polyposis are excluded from the study.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
ORP-101 50 mg
ORP-101 (50 mg) once daily
干预措施: ORP-101 (Drug)
ORP-101 100 mg
ORP-101 (100 mg), once daily
干预措施: ORP-101 (Drug)
Placebo
Matching placebo, once daily
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants Who Are Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain and Daily Stool Consistency Scores
时间窗: Week 12
Composite responders are defined as participants who met the daily response criteria for at least 50% of the days with diary entries over the 12-week interval. A participant must meet both of the following criteria on a given day to be a daily responder: 1) Daily pain response: worst abdominal pain scores in the past 24 hours improved by ≥30% compared to baseline (average of daily worst abdominal pain the week prior to randomization). 2) Average of daily stool consistency response for all reported bowel movements on the specific day: Bristol Stool Scale (BSS) score \<5 (ie, score of 1, 2, 3, or 4) or the absence of a bowel movement if accompanied by ≥30% improvement in worst abdominal pain compared to baseline pain.
次要结局
- Percentage of Participants Who are Responders in IBS Adequate Relief Scores(Week 12)
- Percentage of Participants Who Are Responders in Daily Worst Abdominal Pain Scores(Week 12)
- Percentage of Participants Who Are Responders in Daily Stool Consistency Scores(Baseline to Week 12)
- Percentage of Participants Who are Responders in IBS Global Symptom Scores(Week 12)
- Percentage of Participants Who Are Modified Composite Responders Based on Responder Endpoints(Week 12)
- Change from Baseline in Daily Abdominal Discomfort Scores(Week 12)
- Change from Baseline in Daily Abdominal Bloating Scores(Week 12)
- Number of Bowel Movements Per Day(Week 12)
- Number of Bowel Incontinence Free Days(Week 12)