Clinical trial NCT05643534: Study to Assess Safety and Efficacy of Tenapanor for Treatment of IBS-C in Pediatric Patients 12 to Less Than 18 Years
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Irritable Bowel Syndrome With Constipation (IBS-C)
Keywords: IBS-C
Lead sponsor: Ardelyx
Sponsor class: INDUSTRY
First posted: 2022-12-08
Enrollment: 180
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

* ≥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

Exclusion Criteria:

* 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

Primary outcomes:
measure: 6/12-week APS (abdominal pain and SBM) +2 response
timeFrame: 12 weeks
Secondary outcomes:
measure: 6/12-week SBM +2 response
timeFrame: 12 weeks
measure: 6/12-week abdominal pain response
timeFrame: 12 weeks
measure: Change from baseline in average weekly SBM frequency
timeFrame: 12 weeks
measure: Change from baseline in average weekly stool consistency score
timeFrame: 12 weeks
measure: Change from baseline in average weekly abdominal pain score
timeFrame: 12 weeks
measure: Overall use of rescue medication
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Foley
country: United States
facility: G & L Research, LLC
state: Alabama
city: Tucson
country: United States
facility: Eclipse Clinical Research
state: Arizona
city: Anaheim
country: United States
facility: Advanced Research Center, Inc.
state: California
city: Doral
country: United States
facility: Prohealth Research Center
state: Florida
city: Kissimmee
country: United States
facility: I.H.S. Health, LLC
state: Florida
city: Miami
country: United States
facility: Valencia Medical and Research Center
state: Florida
city: Orlando
country: United States
facility: Orlando Health, Inc.- APH Center for Digestive Health and Nutrition
state: Florida
city: South Miami
country: United States
facility: Florida Pharmaceutical Research and Associates, Inc.
state: Florida
city: Stockbridge
country: United States
facility: Clinical Research Institute
state: Georgia
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Boys Town
country: United States
facility: Boys Town National Research Hospital
state: Nebraska
city: Irvington
country: United States
facility: Med Clinical Research Partners, LLC
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Health Sciences Center
state: New Mexico
city: Bronx
country: United States
facility: Advantage Clinical Trials
state: New York
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: Charlotte
country: United States
facility: Atrium Health
state: North Carolina
city: Raleigh
country: United States
facility: M3 Wake Research, Inc
state: North Carolina
city: Scottdale
country: United States
facility: Frontier Clinical Research, LLC
state: Pennsylvania
city: Smithfield
country: United States
facility: Frontier Clinical Research, LLC
state: Pennsylvania
city: East Greenwich
country: United States
facility: Velocity Clinical Research, Providence
state: Rhode Island
city: Greenville
country: United States
facility: Prisma Health Children's Hospital
state: South Carolina
city: Abilene
country: United States
facility: Advance Clinical Trial PLLC
state: Texas
city: El Paso
country: United States
facility: Maspons Pediatric Gastro
state: Texas
city: El Paso
country: United States
facility: Proactive Clinical Research
state: Texas
city: Harlingen
country: United States
facility: Texas Digestive Specialists
state: Texas
city: Plano
country: United States
facility: AIM Trials, LLC
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
city: Sugar Land
country: United States
facility: Pioneer Research Solutions Inc
state: Texas
city: Waxahachie
country: United States
facility: ClinPoint Trials
state: Texas
city: Huntington
country: United States
facility: University Physicians and Surgeons, Inc.
state: West Virginia
city: Kingwood
country: United States
facility: Frontier Clinical Research
state: West Virginia
Study officials:
affiliation: Ardelyx
name: David Rosenbaum, PhD
role: STUDY_CHAIR
References: