A 12-Week, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Assess the Safety and Efficacy of Tenapanor for the Treatment of Irritable Bowel Syndrome With Constipation (IBS-C) in Pediatric Patients 12 to Less Than 18 Years Old
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Ardelyx
- 入组人数
- 180
- 试验地点
- 64
- 主要终点
- 6/12-week APS (abdominal pain and SBM) +2 response
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled study to assess the efficacy, safety and tolerability of tenapanor (25 mg and 50 mg) in pediatric patients (≥12 and <18 years old) with IBS-C when administered twice daily (BID) for 12 consecutive weeks.
详细描述
This study consists of 2-week screening period followed by 12 week randomized treatment period (RTP) and a 2-week treatment-free Follow-Up period (only for patients who will not enter the 40-week Long Term Safety Extension Study [TEN-01-306]). At the beginning of the 2-week Screening period, patients who provide written assent will be fully assessed for eligibility into the study and will be asked to self-report daily information about the status of their IBS symptoms via an electronic diary (eDiary) device. Patient compliance with the eDiary will be monitored actively by the site staff and will be reviewed to determine eligibility at the end of screening. Eligible patients will be randomized to receive one of the study medications: tenapanor 25 mg BID, tenapanor 50 mg BID, or placebo.
During the 12-week double-blind RTP, patients will continue recording daily assessments via the eDiary system as instructed and compliance with eDiary entries will be monitored on an ongoing basis. Patients will return for study visit every two or four weeks (Visits 3-6) and will undergo safety assessments at these visits.
Patients who do not enter the 40-week Long Term Safety Extension Study [TEN-01-306] including those who complete the RTP but do not enter study TEN-01-306 and those who prematurely discontinue from the RTP, a Follow-Up Visit will be scheduled approximately 2 weeks after the completion of the RTP (Visit 6) or the Early Termination Visit at which safety assessments will be performed
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
- 12 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥12 and <18 years old
- •Patient weighs ≥18 kg at the time the patient provides written assent
- •Females of child-bearing potential must have negative pregnancy test at Visit 1 (serum) and Visit 2 (urine) and confirm the use of appropriate contraception (including abstinence).
- •Patient meets the Rome IV criteria for child/adolescent diagnosis of IBS-C
- •Patient is willing to discontinue any laxatives used in favor of the protocol-permitted rescue medicine (which will only be allowed after 72 hours with no bowel movement)
- •Patient meets the entry criteria assessed during the 2-week Screening period.
- •Ability of both the patient and parent/guardian/LAR to communicate with the Investigator and to comply with the requirements of the entire study, including an understanding of the assessments in the eDiary and how to use the eDiary device
- •Patient must provide written assent and the parent/guardian/LAR must provide written informed consent before the initiation of any study-specific procedures
排除标准
- •Functional diarrhea as defined by Rome IV child/adolescent criteria
- •IBS with diarrhea (IBS-D), mixed IBS (IBS-M), or unsubtyped IBS as defined by Rome IV child/adolescent criteria
- •History of non-retentive fecal incontinence.
- •Required manual disimpaction any time prior to randomization (after consent);
- •Has both unexplained and clinically significant alarm symptoms (lower gastrointestinal [GI] bleeding [rectal bleeding or heme-positive stool], iron-deficiency anemia, or any unexplained anemia, or weight loss) and systemic signs of infection or colitis, or any neoplastic process
- •Patient has any of the following conditions:
- •Celiac disease, or positive serological test for celiac disease
- •Cystic fibrosis
- •Hypothyroidism that is untreated or treated with thyroid hormone
- •Down's syndrome or any other chromosomal disorder
- •Active anal fissure
- •Anatomic malformations (eg, imperforate anus)
- •Intestinal nerve or muscle disorders (eg, Hirschprung disease)
- •Neuropathic conditions (eg, spinal cord abnormalities)
- •Lead toxicity, hypercalcemia
- •Neurodevelopmental disabilities producing a cognitive delay that precludes comprehension and completion of the daily eDiary (Electronic handheld device)
- •Inflammatory bowel disease
- •Childhood functional abdominal pain syndrome
- •Childhood functional abdominal pain;
- •Poorly treated or poorly controlled psychiatric disorders that might influence his or her ability to participate in the study;
- •Lactose intolerance that is associated with abdominal pain or discomfort
- •History of cancer other than treated basal cell carcinoma of the skin; (Note: Patients with a history of cancer are allowed provided that the malignancy has been in a complete remission for at least 5 years before the Randomization Visit.)
- •History of diabetic neuropathy.
- •Use of medications that are known to affect stool consistency (Prohibited Medications), including fiber supplements, anti-diarrheals, cathartics, antacids, opiates, prokinetic drugs, laxatives, enemas, antibiotics during the Screening period; unless specified as rescue medication, and used accordingly as directed by the Investigator.
- •Patient has had surgery that meets any of the following criteria:
- •Bariatric surgery for treatment of obesity, or surgery to remove a segment of the GI tract at any time before the Screening Visit;
- •Surgery of the abdomen, pelvis, or retroperitoneal structures during the 6 months before the Screening Visit;
- •An appendectomy or cholecystectomy during the 60 days before the Screening Visit;
- •Other major surgery during the 30 days before the Screening Visit
- •History of alcohol or substance abuse
- •Participation in other clinical trials within 1 month prior to Screening
- •Patient and/or parent/guardian/LAR is involved in the conduct and/or administration of this trial as an investigator, sub-investigator, trial coordinator, or other staff member, or the patient is a first-degree family member, significant other, or relative residing with one of the above persons involved in the trial
- •If, in the opinion of the Investigator, the patient is unable or unwilling to fulfill the requirements of the protocol or has a condition, which would render the results uninterpretable
研究组 & 干预措施
Tenpanor 50 mg BID
Patients will be randomized to receive 50 mg tenapanor twice daily
干预措施: Tenapanor 50 MG (Drug)
Tenpanor 25 mg BID
Patients will be randomized to receive 25 mg tenapanor twice daily
干预措施: Tenapanor 25 mg bid (Drug)
Placebo Comparator
Patients will be randomized to receive matching placebo twice daily
干预措施: Placebo (Drug)
结局指标
主要结局
6/12-week APS (abdominal pain and SBM) +2 response
时间窗: 12 weeks
6/12-week APS (abdominal pain and SBM (spontaneous bowel movement)) +2 response, defined as achieving the weekly APS +2 response criteria (i.e., achieving both weekly SBM +2 response and weekly abdominal pain response during the same week) for ≥6 out of the 12 weeks of the RTP. * The weekly SBM +2 response is defined as having an increase of ≥2 from baseline in the average weekly SBM frequency for a given week * The weekly abdominal pain response is defined as having ≥30% reduction from baseline in the average weekly abdominal pain score for a given week
次要结局
- 6/12-week SBM +2 response(12 weeks)
- 6/12-week abdominal pain response(12 weeks)
- Change from baseline in average weekly SBM frequency(12 weeks)
- Change from baseline in average weekly stool consistency score(12 weeks)
- Change from baseline in average weekly abdominal pain score(12 weeks)
- Overall use of rescue medication(12 weeks)