3030-401-002: An Open-Label Pilot Study of Eluxadoline in Participants With Irritable Bowel Syndrome With Diarrhea (IBS-D) Who Have Evidence of Bile Acid Malabsorption (BAM)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Allergan
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Number of Participants Who Experienced Potentially Clinically Significant Change in Laboratory Tests
研究概览
简要总结
This study will evaluate the possibility of a differential effect of eluxadoline on altered bowel function in Irritable Bowel Syndrome with Diarrhea (IBS-D) participants with and without evidence of Bile Acid Malabsorption (BAM).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •Adult men or women aged 18 to 75 years inclusive with a diagnosis of IBS-D per Rome IV criteria.
- •Participants with evidence of BAM must have a fasting serum 7a-hydroxy-4-cholesten-3-one (7αC4) level ≥ 52.5 ng/mL or total fecal bile acid (BA) > 2337 micromoles/48 hours (positive result) at screening or within 1 calendar year prior to screening.
- •Participants without BAM must have a fasting serum 7αC4 level ≤ 47.1 ng/mL or total fecal BA < 2200 micromoles/48 hours (negative result) at screening or within 1 calendar year prior to screening.
- •Has an average daily Bristol Stool Form Scale (BSFS) score ≥ 5.0 or ≥ 25% of diary entry days with a BSFS score of 6 or 7 during the 14 days prior to Day
- •Women of childbearing potential must use hormonal or double barrier contraception or maintain a monogamous relationship with a vasectomized male partner from the date of informed consent until 24 hours after final dose of study drug.
- •Completed the electronic diary (eDiary) on ≥ 10 of the 14 days prior to Day
- •Has not used loperamide rescue medication on > 3 of the 14 days prior to Day 1.
排除标准
- •Has a diagnosis of IBS with a subtype of irritable bowel syndrome with constipation (IBS-C), mixed IBS, or unsubtyped IBS per Rome IV criteria.
- •Does not have a gallbladder.
- •Has known or suspected biliary duct obstruction, or sphincter of Oddi disease or dysfunction. (Participants with a history of gallstones may be enrolled).
- •Has a history of alcoholism, alcohol abuse or alcohol addiction, or drinks more than 3 alcoholic beverages per day.
- •Has a history of pancreatitis; structural diseases of the pancreas, including known or suspected pancreatic duct obstruction.
- •Has a history of mild, moderate, or severe hepatic impairment according to Child-Pugh classification. History or current diagnosis of inflammatory or immune-mediated gastrointestinal (GI) disorders.
- •Has Celiac disease or a positive serological test for celiac disease.
- •Has known lactose or fructose intolerance associated with diarrhea, abdominal pain or discomfort, that could confound assessments in the study.
- •Women who are currently pregnant or nursing, or plan to become pregnant or nurse during the study.
- •Has known allergies or hypersensitivity to opioids.
研究组 & 干预措施
Eluxadoline 100 mg with BAM
IBS-D participants with evidence of Bile Acid Malabsorption (BAM) treated with eluxadoline 100 mg oral tablets twice daily (BID) with food for 4 weeks.
干预措施: Eluxadoline (Drug)
Eluxadoline 100 mg without BAM
IBS-D participants without evidence of BAM treated with eluxadoline 100 mg oral tablets BID with food for 4 weeks.
干预措施: Eluxadoline (Drug)
结局指标
主要结局
Number of Participants Who Experienced Potentially Clinically Significant Change in Laboratory Tests
时间窗: Baseline (Day 1) to Week 4
Laboratory tests included tests of Clinical Chemistry, Hematology, and Urinalysis. The investigator determined if the result was potentially clinically significant.
Number of Participants Who Experienced Potentially Clinically Significant Change in Vital Signs
时间窗: Baseline (Day 1) to Week 4
Vital signs assessments included: pulse, respiratory rate, and blood pressure (systolic and diastolic). The investigator determined if the result was potentially clinically significant.
Number of Participants Who Experienced Clinically Significant Change From Baseline in General Physical Condition as Measured Through General Physical Exam
时间窗: Baseline (Day 1) to Week 4
General Physical Examination consisted of a full review of body systems excluding pelvic and rectal exams. The investigator determined if the result was clinically significant.
Change From Baseline in Average Bristol Stool Form Scale (BSFS) Score Over 4 Weeks of Treatment Period
时间窗: Baseline (Day 1) to Week 4
Stool consistency was assessed using the BSFS where: 1=Separate hard lumps like nuts to 7=Watery. The score was recorded by the participant in an electronic diary (e-diary). The score for each day was averaged over the 4-week period. A negative change from Baseline indicates improvement.
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: Baseline (Day 1) to Week 4
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is an AE that occurs or worsens after receiving investigational study drug.
次要结局
- Change From Baseline in the 4-week Average of Daily Bowel Movement Frequency During the Treatment Period(Baseline (Day 1) to Week 4)
- Change From Baseline in the 4-week Average of Daily Worst Abdominal Pain Scores During the Treatment Period(Baseline (Day 1) to Week 4)
- Change From Baseline in the 4-week Average of Daily Bloating Scores During the Treatment Period(Baseline (Day 1) to Week 4)
- Change From Baseline in the 4-week Average Number of Daily Urgent Bowel Movements During the Treatment Period(Baseline (Day 1) to Week 4)
- Percentage of Participants With Any Fecal Incontinence During the Treatment Period(Baseline (Day 1) to Week 4)
- Change From Baseline in Irritable Bowel Syndrome Quality of Life (IBS-QOL) Total Score at the End of the Treatment Period(Baseline (Day1) to End of Treatment (Up to Week 4))
- Change From Baseline in Fasting Serum 7α-hydroxy-4-cholesten-3-one (7αC4) Levels at the End of the Treatment Period(Baseline (Day 1) to End of Treatment (Up to Week 4))
- Cmax: Maximum Concentration for Eluxadoline(Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2)
- Cmin: Minimum Concentration for Eluxadoline(Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2)
- AUC: Area Under the Concentration-time Curve During the Dosing Interval for Eluxadoline(Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2)
- Tmax: Time to Cmax for Eluxadoline(Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2)
- t1/2: Half-Life for Eluxadoline(Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2)
- CL/F: Apparent Total Clearance of the Drug From Plasma After Oral Administration for Eluxadoline(Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2)
- Vc/F: Apparent Volume of Distribution for Eluxadoline(Predose and at the intervals 1-2, 3-4 and 5-8 hours postdose at Week 2)