A Phase 3b, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial of Linaclotide 290 μg Administered Orally for 12 Weeks Followed by a 4-week Randomized Withdrawal Period in Patients With Irritable Bowel Syndrome With Constipation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 614
- 试验地点
- 77
- 主要终点
- Overall Change From Baseline in Abdominal Score (Abdominal Bloating, Abdominal Discomfort, and Abdominal Pain) Throughout the Treatment Period
研究概览
简要总结
To evaluate the efficacy on abdominal symptoms (abdominal bloating, abdominal discomfort, and abdominal pain) and safety of linaclotide 290 μg administered orally to patients with IBS-C.
详细描述
This study consists of a 12-week Treatment Period followed by 4-week Randomized Withdrawal (RW) Period.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient has no clinically significant findings on a physical examination and clinical laboratory tests
- •Female patients of childbearing potential must agree to use one of the following methods of birth control:
- •Hormonal contraception
- •Double-barrier birth control
- •Maintenance of a monogamous relationship with a male partner who has been surgically sterilized by vasectomy
- •Patient meets protocol criteria for diagnosis of IBS-C
- •Patient demonstrates continued IBS-C symptoms through Pretreatment Period
- •Patient maintains a minimum level of compliance with daily diary
排除标准
- •Patient has history of loose or watery stools
- •Patient has symptoms of or been diagnosed with a medical condition that may contribute to abdominal pain
- •Patient has a structural abnormality of the gastrointestinal (GI) tract or a disease or condition that can affect GI motility
- •Patient has any protocol-excluded or clinically significant medical or surgical history that could confound the study assessments
研究组 & 干预措施
Linaclotide 290 µg
Participants receive linaclotide 290 µg orally once daily for 12 weeks during the Treatment Period. At Week 12 participants are rerandomized to receive either linaclotide 290 µg or placebo for 4 weeks in the Randomized Withdrawal Period.
干预措施: Linaclotide (Drug)
Linaclotide 290 µg
Participants receive linaclotide 290 µg orally once daily for 12 weeks during the Treatment Period. At Week 12 participants are rerandomized to receive either linaclotide 290 µg or placebo for 4 weeks in the Randomized Withdrawal Period.
干预措施: Placebo (Drug)
Placebo
Participants receive placebo to linaclotide orally once daily for 12 weeks during the Treatment Period. At Week 12 participants are switched to receive linaclotide 290 µg for 4 weeks during the Randomized Withdrawal Period.
干预措施: Linaclotide (Drug)
Placebo
Participants receive placebo to linaclotide orally once daily for 12 weeks during the Treatment Period. At Week 12 participants are switched to receive linaclotide 290 µg for 4 weeks during the Randomized Withdrawal Period.
干预措施: Placebo (Drug)
结局指标
主要结局
Overall Change From Baseline in Abdominal Score (Abdominal Bloating, Abdominal Discomfort, and Abdominal Pain) Throughout the Treatment Period
时间窗: Baseline (14 days before randomization up to the time of randomization), Treatment Period (Weeks 1-12)
A participant's daily abdominal score was calculated as the average of daily e-diary abdominal pain, abdominal bloating and abdominal discomfort scores, each based on an 11-point scale of 0 (none) and 10 (worst possible). Baseline abdominal score was derived from the eDiary data collected daily in the Pretreatment Period, specifically the period of time from 14 days before randomization up to the time of randomization. The participant's abdominal score was averaged on a weekly basis, and each weekly change from baseline was calculated for the treatment period and used as the dependent variable in the mixed model with repeated measures (MMRM) model. MMRM results are based on a model with treatment, analysis week, region and treatment-by-week interaction as fixed effects and baseline as a covariate. An unstructured covariance structure was used to model intra-subject correlation with subjects as a random effect.
次要结局
- Overall Change From Baseline in Abdominal Score (Abdominal Bloating, Abdominal Discomfort, and Abdominal Pain) Over Time in the Treatment Period(Baseline (14 days before randomization up to the time of randomization), Weeks 1-12)
- Cumulative Distribution of Change From Baseline in 12-Week Abdominal Score(Baseline (14 days before randomization up to the time of randomization), Treatment Period (Weeks 1-12))
- Percentage of 6/12 Week Abdominal Score Responders (Responder Rate)(Baseline (14 days before randomization up to the time of randomization), Treatment Period (Weeks 1-12))