A Randomized, 12-Week, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Assess the Safety and Efficacy of Plecanatide in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 428
- 试验地点
- 97
- 主要终点
- Change From Baseline in Weekly CSBMs Frequency Over the 12-Week Treatment Period (mITT Population)
研究概览
简要总结
This is a randomized, 12-week, double-blind, placebo-controlled, dose-ranging study in patients with IBS-C.
详细描述
This is a randomized, 12-week, double-blind, placebo-controlled, dose-ranging study in patients with IBS-C. Patients will undergo a Screening Period to determine eligibility. After completing a Screening Visit patients will undergo a 2-week Pre-Treatment assessment using the Interactive Voice Response System (IVRS) during which they will complete daily assessments of bowel movements (BMs), stool consistency (Bristol Stool Form Scale- BSFS), abdominal pain or abdominal discomfort and other symptoms associated with IBS-C. Data from the two-week IVRS Pre-treatment assessment are used to define the patient's baseline from which change will be determined. Patients who meet all entry criteria will be randomized to one of five treatment groups ( 0.3mg,1.0mg,3.0mg,9mg,or Placebo) on Day 1 of the Treatment Period. Patients will take an oral dose of study drug daily (QD) for 12 weeks and continue the daily IVRS diaries (BMs, abdominal pain, other symptoms). On Weeks 2, 4, 8, and 12, patients will return to the clinic to undergo safety and efficacy assessments. For 2 weeks after completing dosing, (i.e., Post-Treatment Period), patients will continue to complete daily IVRS diaries. Patients will then return to the clinical site for a final follow-up visit (End of Study Visit). The planned duration of participation in this study will be approximately 112 days from signing of informed consent through post-treatment or 145 days if 30 day washout of a prohibited concomitant medication or stabilization of a medical condition is required before Pre-Treatment (up to 148 days, with all windows considered).
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged 18-75, inclusive
- •Body Mass Index = 18-35 kg/m2, inclusive
- •Meets modified Rome III criteria for irritable bowel syndrome with constipation which includes abdominal pain or discomfort for at least 3 days/month in the last 3 months with symptom onset for at least 6 months.
- •Less than 3 CSBMs and less than 6 SBMs per week during the last 3 months.
- •Hard or lumpy stools ≥ 25 % of defecations
- •Patient has average abdominal pain intensity scores ≥ 3 (scale 0-10)for the combined 2 week pre-treatment period
- •Patient is willing to discontinue use of supplemental fiber, laxatives, prescription and nonprescription medications, herbal or dietary supplements intended to treat constipation during the screening, pre-treatment, treatment and 2-week post-treatment periods
- •Willing to maintain a stable diet during the study.
- •Patients with hemorrhoids and/or diverticulosis (NOT diverticulitis) CAN be entered into the study.
排除标准
- •Loose stool (mushy) or watery stool in the absence of any laxative or prohibited medicine for > 25% of BMs during the 3 months prior to screening visit OR during the 14 day pre-treatment period
- •Patient has diarrhea-predominant or mixed ( diarrhea and constipation cycling or diarrhea and normal cycling) IBS.
- •Active peptic ulcer disease not adequately treated or not stable
- •History of cathartic colon, laxative, enema abuse, or ischemic colitis.
- •Fecal impaction within 3 months of screening
- •Patient has had /has any: structural abnormality of the GI tract or gastric bypass surgery, pelvic floor dysfunction, pseudo-obstruction, active infectious gastritis, diverticulitis, anal fissures or any disease or condition that can affect GI motility or defecation or can be associated with abdominal pain
- •Unexplained and clinically significant "alarm symptoms" including lower GI bleeding, iron-deficiency anemia, weight loss or systemic signs of infection or colitis.
- •Major surgery within 60 days of screening.
研究组 & 干预措施
Plecanatide 0.3mg
Plecanatide 0.3mg, one tablet by mouth daily for 12 weeks
干预措施: Plecanatide (Drug)
Plecanatide 1.0mg
Plecanatide 1.0mg one tablet by mouth daily for 12 weeks
干预措施: Plecanatide (Drug)
Plecanatide 3.0mg
Plecanatide 3.0mg, one tablet by mouth daily for 12 weeks
干预措施: Plecanatide (Drug)
Plecanatide 9.0mg
Plecanatide 9.0mg, one tablet by mouth daily for 12 weeks
干预措施: Plecanatide (Drug)
Placebo
Placebo, one tablet by mouth daily for 12 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Weekly CSBMs Frequency Over the 12-Week Treatment Period (mITT Population)
时间窗: 12 weeks Treatment Period
The primary efficacy endpoint was the change from baseline in the weekly CSBM frequency (CSBMs per week minus CSBMs per week at baseline) over a 12-week Treatment Period. A Complete Spontaneous Bowel Movement (CSBM) is a Bowel Movement (BM) that occurs in the absence of laxative use within 24 hours of the BM and the patient reports a feeling of complete evacuation.
次要结局
- Change From Baseline in Abdominal Pain Intensity Scores Over 12-Week Treatment Period (mITT Population)(12-Week Treatment Period)
- Change From Baseline in Stool Consistency (BSFS) Over 12-Week Treatment Period (mITT Population)(12-Week Treatment Period)
- Change From Baseline in Straining Scores Over 12-Week Treatment Period (mITT Population)(12-Week Treatment Period)