A Double-blind, Randomised, Placebo-controlled, Phase 3 Trial in Patients With Chronic Idiopathic Constipation to Demonstrate the Efficacy and Safety of Elobixibat 5 mg and 10 mg for 12 Weeks Followed by a 4-week Withdrawal Period
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 314
- 试验地点
- 92
- 主要终点
- Overall Complete Spontaneous Bowel Movement (CSBM) Response
研究概览
简要总结
12 Week Efficacy and Safety Trial Followed by a 4 Week Withdrawal Period for Patients with Chronic Idiopathic Constipation.
详细描述
The present trial was designed to determine the efficacy and safety of elobixibat treatment (at both doses of 5 mg and 10 mg/day) compared to placebo treatment for 12-week Treatment Period followed by a 4-week Withdrawal Period in patients with chronic idiopathic constipation. During Withdrawal Period a sub-group of patients in elobixibat 5 mg and 10 mg treatment arms respectively received placebo treatment, while rest of the patients continued with 5 mg and 10 mg treatment in respective groups. In placebo groups, patients received elobixibat 10 mg treatment during Withdrawal Period. Patients were followed-up for 2 weeks after end of the Withdrawal Period.
The assessment of primary and key secondary end points was done for patients who completed the first 12 weeks of treatment period. Incidence of Adverse Events (AEs) were reported till 2 weeks after end of the Withdrawal Period.
The trial was early terminated due to a distribution issue with the trial medication.
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
- •Body mass index (BMI) ≥18.5 but <35.0 kg/m^2
- •Male or female ≥18 years of age
- •Reports <3 spontaneous Bowel Movements (BM) per week and reports one or more of the following symptoms for the last 3 months with symptom onset at least 6 months before the Screening Visit or before starting chronic therapy with any laxative:
- •Straining during at least 25% of defecations
- •Lumpy or hard stools during at least 25% of defecations
- •Sensation of incomplete evacuation during at least 25% of defecations
- •Is ambulatory and community dwelling
- •An initial colonoscopy is required if recommended by national guidelines
排除标准
- •Reports loose (mushy) or watery stools in the absence of any laxative intake in the form of a tablet, a suppository or an enema, or prohibited medicine for >25% of BMs
- •The patient reports a BSFS of 6 or 7 during the Pretreatment Period
- •Has irritable bowel syndrome (IBS) with pain/discomfort as predominant symptoms
- •Has a structural abnormality of the Gastrointestinal (GI) tract or a disease or condition that can affect GI motility
- •Has a history of diverticulitis, chronic pancreatitis, active peptic ulcer disease (PUD) not adequately treated, ischaemic colitis, inflammatory bowel disease, laxative abuse, faecal impaction that required hospitalization or emergency treatment, pseudo-obstruction, megacolon, megarectum, bowel obstruction, descending perineum syndrome, ovarian cysts, endometriosis, solitary rectal ulcer syndrome, systemic sclerosis, pre-malignant colonic disease (e.g., familial adenomatous polyposis or hereditary non-polyposis colorectal cancer) or other forms of familial colorectal cancer
- •Has unexplained and clinically significant GI alarm signals (e.g., lower GI bleeding or heme-positive stool in the absence of known internal or external haemorrhoids, iron-deficiency anaemia, unexplained weight loss) or systemic signs of infection or colitis
- •Has a potential central nervous system (CNS) cause of constipation (e.g., Parkinson's disease, spinal cord injury, multiple sclerosis)
- •Has intestinal/rectal prolapse or other known pelvic floor dysfunction
- •Commonly uses digital maneuvers (perianal pressure or digital disimpaction) or vaginal splinting to facilitate the passage of a bowel movement
- •Has a history of diabetic neuropathy
- •Has a history of bariatric surgery for treatment of obesity; surgery to remove a segment of the GI tract; or surgery of the abdomen, pelvic or retroperitoneal area during the 6 months prior to Screening; or appendectomy or cholecystectomy 3 months prior to screening; or other major surgery 1 month prior to Screening
- •Has a history of cancer with last date of proven disease activity/presence of malignancy within 5 years, except for adequately treated basal cell carcinoma of the skin, cervical dysplasia, or carcinoma in situ of the skin or the cervix
- •Known human immunodeficiency virus (HIV) or Hepatitis B/C (HBV/HCV) infection
- •Has a history of hospitalization for any psychiatric disorder, or any suicide attempt in the 2 years prior to Screening
- •Is actively abusing alcohol or drugs or has a history of alcohol or drug abuse during the 6 months prior to Screening
- •Is being treated for hypothyroidism, but the dose of medication has not been stable for at least 3 months at the time of Screening
- •Is a pregnant, breast-feeding, or lactating woman
研究组 & 干预措施
EBX 10
Elobixibat 10 mg/day
干预措施: Elobixibat 10 mg/day (Drug)
EBX 5
Elobixibat 5 mg/day
干预措施: Elobixibat 5 mg/day (Drug)
PLCBO
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Overall Complete Spontaneous Bowel Movement (CSBM) Response
时间窗: During the first 12 weeks
This outcome measured the percentage of patients who were CSBM responders. A CSBM responder was defined as a patient with ≥3 CSBMs per week and an increase of ≥1 CSBM per week from Baseline, for at least 9 of the 12 weeks in the 12-week Treatment Period, including at least 3 weeks during Weeks 9-12.
次要结局
- Change From Baseline in Weekly Frequency of Spontaneous Bowel Movement (SBMs)(From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period)
- Change From Baseline in Weekly Stool Consistency of SBMs(From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period)
- Occurrence of CSBM Response(Within first 24 hours of treatment initiation)
- Change From Baseline in Weekly Abdominal Discomfort Score(From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period)
- Change From Baseline in Weekly Degree of Straining of SBMs(From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period)
- Change From Baseline in Weekly Abdominal Bloating Score(From Baseline (2-week Pretreatment Period) to overall first 12-weeks of Treatment Period)
- Total Patient Assessment of Constipation - Quality of Life (PAC-QOL) Score Responder(At Week 12)