A Randomized, Double-Blind, Multicentric, Placebo-Controlled, Parallel Group Clinical Trial to Evaluate the Efficacy and Safety of Plecanatide in Subjects with Chronic Idiopathic Constipation or Irritable Bowel Syndrome with Constipation.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 210
- 试验地点
- 11
- 主要终点
- Proportion (%) of the subjects having an average of at least three or more complete spontaneous bowel movements (CSBMs)/week over the 12 weeks of the treatment period.
研究概览
简要总结
This will be a double blind, prospective, study to evaluate safety and efficacy of Plecanatide in subjects with chronic idiopathic constipation or irritable bowel syndrome with constipation. Initially subjects will be screened as per predefined eligibility criteria for the study. Eligible 210 subjects will be enrolled to receive either Plecanatide or placebo.
Subjects will be randomized in 2:1 ratio. Group 1 will have 140 subjects and Group 2 will have 70 subjects.
Group 1 (Treatment group): Plecanatide.
Group 2 (Control group): Placebo
The study will involve screening (Day -14), treatment period of up to maximum 12 weeks till end of study. The investigator shall make every effort to follow the schedule of study assessments and procedures. A window period of ±1 day will be allowed for assessments post randomization.
Screening:
Upon obtaining the written informed consent the subjects will be screened to confirm the eligibility for participating in this study. Subjects will undergo 14 days of pretreatment where they will record number of spontaneous bowel movements and use of rescue medication during this period. In baseline visit (Day 0) randomization will be performed.
Treatment period:
Subjects will receive investigational product Plecanatide or placebo after randomization as per protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Male or female subjects having age 18 years to 65 years.
- •Subject and/or his/her legally accepted representative willing to give written informed consent.
- •Subjects with a diagnosis of chronic idiopathic constipation as per Rome IV criteria.
- •According to the Rome IV criteria for constipation, a patient must have experienced at least two of the following symptoms over the preceding three months with symptom onset at least 6 months prior to diagnosis: i) Fewer than three spontaneous bowel movements per week.
- •ii) Straining for more than 25% of defecation attempts.
- •iii)Lumpy or hard stools for at least 25% of defecation attempts iv) Sensation of anorectal obstruction or blockage for at least 25% of defecation attempts.
- •v) Sensation of incomplete defecation for at least 25% of defecation attempts.
- •vi) Manual manoeuvring required to defecate for at least 25% of defecation attempts.
- •History of poor results with laxative treatment and diet counselling (Subjects on a stable diet regimen at the time of screening visit and are willing to continue the same diet for the the entire duration of the study).
- •Subjects who report fewer than three complete spontaneous bowel movement (CSBMs) per week during pre-treatment period of 2 weeks after screening (verified at the time of enrolment visit).
排除标准
- •Subject with history of hypersensitivity to Plecanatide or to any of the excipient.
- •Subject with mechanical bowel obstruction, megacolon/megarectum, or diagnosis of pseudo-obstruction.
- •(as per documented colonoscopy).
- •Subjects with known or suspected organic disorders of the large or small bowel (e.g., inflammatory bowel disease like ulcerative colitis, Crohn’s Disease).
- •Subjects with history of weight loss 10% of body weight over a period of 6 months.
- •Subjects having history of anemia and hemoglobin (Hb) ≤12.5 gm/dl for male or Hb ≤12 gm/dl for female at screening laboratory investigation.
- •Subjects on treatment with drugs which are likely to cause constipation e.g., tricyclic antidepressants, anticholinergics, narcotic analgesics or calcium channel blockers.
- •Subjects with active peptic ulcer.
- •Subject with history of bowel resection or rectal bleeding.
- •Subject with history of Hospitalization for any gastrointestinal or abdominal surgical procedure during the 3 months prior to screening.
- •Subjects with TSH ≥6 µIU/ml or symptoms of hyperthyroidism or hypothyroidism and the same confirmed with laboratory investigation.
- •Subjects with clinically significant ECG abnormalities.
- •Clinically significant medical disorder or clinically significant abnormal laboratory finding.
- •History of faecal impaction that required hospitalization or has a history of laxative or enema abuse, ischemia colitis and pelvic floor dysfunction.
- •Subjects with liver enzymes (ALT and AST) more than 2.5 times the normal value and/or bilirubin more than 1.5 times the normal value.
- •Subject with Serum creatinine more than upper limit of normal value (UNL).
- •Subject with history of malignancy except basal cell carcinoma.
- •Pregnant or lactating women.
- •Female subjects who are of childbearing potential and who are neither surgically sterilized nor willing to use reliable contraceptive methods (hormonal, barrier methods or intrauterine device).
- •Participation in any clinical study during last three months.
- •Subjects with suspected signs and symptoms of COVID-19/confirmed novel coronavirus infection (COVID-19) or with a recent history of travel/contact with any COVID-19 positive subject /isolation/quarantine in the last 14 days based on investigator’s discretion.
结局指标
主要结局
Proportion (%) of the subjects having an average of at least three or more complete spontaneous bowel movements (CSBMs)/week over the 12 weeks of the treatment period.
时间窗: Baseline, Week 1, Week 6, Week 12
次要结局
- Improvement in weekly average score of straining from baseline to week 12 using 11-point scale.(Baseline, Week 1, Week 6, Week 12)
- Improvement in weekly average score of stool consistency from baseline to Week 12 using Bristol Stool Form scale.(Baseline, Week 1, Week 6, Week 12)
- Proportion (%) of bowel movements with incomplete evacuation/week(Baseline, Week 1, Week 6, Week 12)
- Frequency of rescue therapy (bisacodyl) used per week for constipation.(Baseline, Week 1, Week 6, Week 12)
- Improvement in Investigator’s global assessment of efficacy at week 1, week 6 and week 12 using 5-point scale.(week 1, week 6 and week 12)