Overview
This is a randomized, double-blind, placebo-controlled dose-ranging study to assess the safety and efficacy of tenapanor for treatment of the IBS-C in pediatric patients 6 to less than 12 year old.
Description
This study consists of 2 week screening period in which subjects who have consented will be evaluated for eligibility per protocol requirements. During this 2 week screening period subjects will be given access to ediary in which they will be required to self report symptoms of IBS-C daily. Information in ediary will also be used to determine eligibility prior to enrollment.
During the 4 week RTP (Randomized treatment period), subjects will be randomized in in a ratio of 5:1 to receive tenapanor or matching placebo for 4 weeks. During the RTP, patients will continue recording daily assessments in the eDiary system as instructed and compliance with eDiary entries will be monitored. Patients will return for study visit every weeks (Visits 3-6) and will undergo safety assessments as per the protocol. At the end of this 4 week period, subjects will complete 2 week treatment free follow-up period and safety assessments per protocol will be conducted at the end of this 2 week period.
The study plans to enroll up to 6 cohorts of eligible patients sequentially, starting from Cohort 1 with 12 patients randomized in to receive tenapanor 2 mg BID or matching placebo for 4 weeks. Subsequent cohorts will assess increasing tenapanor doses, following a dose escalation order. The study will proceed to the next dosing cohort if the current cohort completes the 4-week RTP and does not meet any of the dose escalation stopping criteria pre-specified in the protocol.
Eligibility
Inclusion Criteria:
- ≥6 and <12 years old at the Screening visit (Visit 1)
- Confirmation of negative pregnancy test and use of appropriate contraceptive (including abstinence) in female subjects that have experienced menarche and are of child-bearing potential.
- Meet the Modified Diagnostic 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)
- Meet 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 verbal assent and the parent/guardian/LAR must provide written informed consent before the initiation of any study-specific procedures
Exclusion Criteria:
- Functional diarrhea as defined by Modified Rome IV child/adolescent criteria
- IBS with diarrhea (IBS-D), mixed IBS (IBS-M), or unsubtyped IBS as defined by Modified Rome IV child/adolescent criteria
- History of non-retentive fecal incontinence;
- Required manual disimpaction any time prior to randomization (after consent)
- Currently 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 and the condition has not been ruled out by endoscopic biopsy;
- Cystic fibrosis;
- Hypothyroidism that is untreated or treated with thyroid hormone at a dose that has not been stable for at least 3 months prior to the Screening Visit;
- Down's syndrome or any other chromosomal disorder;
- Active anal fissure (Note: History of anal fissure is not an exclusion);
- Anatomic malformations (eg, imperforate anus, anal stenosis, anterior displaced anus);
- Intestinal nerve or muscle disorders (eg, Hirschprung disease, visceral myopathies, visceral neuropathies);
- Neuropathic conditions (eg, spinal cord abnormalities, neurofibromatosis, tethered cord, spinal cord trauma);
- Lead toxicity, hypercalcemia;
- Neurodevelopmental disabilities
- 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 and could confound the assessments in this study
- History of cancer other than treated basal cell carcinoma of the skin;
- 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:
- 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