A Study to Assess Adverse Events and Change in Disease Activity in Pediatric Participants (Age 6 Months to <2 Years) With Functional Constipation Who Are Treated With Linaclotide

A Phase 2 Dose Finding Study Evaluating the Safety and Efficacy of Linaclotide in Pediatric Subjects 6 Months to Less Than 2 Years of Age With Functional Constipation (FC).

Functional constipation (FC) is a common healthcare problem in children of all ages, potentially due to genetic predisposition, inadequate fiber and fluid intake, and immobility. Currently, there are no pharmacological therapies approved for the treatment of FC. This study will assess adverse events and change in disease activity with linaclotide therapy in participants with FC.

Linaclotide is an approved drug being developed for the treatment of FC in pediatric patients who meet modified Rome IV criteria for childhood FC. In Part 1 of this study, participants are placed in 3 groups, which occur consecutively. Each group receives a different dosage of linaclotide. In Part 2 of the study, participants will be randomly assigned to receive either linaclotide or placebo. There is a 1 in 2 chance that participants will be assigned to placebo. Up to 30 and at least 18 pediatric participants 6 months to less than 2 years of age with FC will be enrolled in the study at approximately 38 sites worldwide.

Participants will receive oral solution of linaclotide prepared from capsule by parent/guardian once daily for 4 weeks.

There may be higher treatment burden for participants in this trial compared to their standard of care (due to study procedures). Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Inclusion Criteria:

• Individuals must be 6 months to less than 1 year and 11 months old, at the time the legally authorized representative (LAR)/parent/guardian signs the informed consent in alignment with local requirements.

• The LAR/parent/guardian who will be completing the electronic diary (eDiary) is able to read and understand the assessments in the eDiary device and must undergo training.

• Participant meets Rome IV criteria for functional constipation (FC): for at least 1 month before Screening (Visit 1), the participant must meet 2 or more of the following:

  • 2 or fewer defecations per week (with each defecation occurring in the absence of any laxative, suppository, or enema use during the preceding 24 hours)
  • History of excessive stool retention
  • History of painful or hard bowel movements (BMs)
  • History of large-diameter stools
  • Presence of a large fecal mass in the rectum

• LAR/Parent/Guardian is willing to discontinue any laxatives used before the Preintervention Visit in favor of the protocol-permitted rescue medicine.

Exclusion Criteria:

• Participant has conditions that could interfere with drug absorption, including, but not limited to, short bowel syndrome.

• History of clinically significant medical conditions or any other reason that the investigator determines would interfere with the individual's participation in this study or would make the participant an unsuitable candidate to receive study drug.

• Participant has history of:

  • Celiac disease, or positive serological test for celiac disease or the condition is suspected but 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 Screening (Visit 1)
  • Down's syndrome or any other chromosomal disorder
  • Active anal fissure (investigator has confirmed an active anal fissure and participant reports known anal fissure symptoms [i.e., streaks of blood on the stool or on diaper or toilet paper and pain/crying with bowel movement within 2 weeks prior to Screening]). (Note: Anal fissures that have resolved at least 2 weeks prior to screening would not be exclusionary). However, if in the investigator's opinion, an anal fissure(s) may be the primary cause of participant's Rome IV FC criteria, the subject would not be eligible to participate in the study.
  • Anatomic malformations (e.g., imperforate anus, anal stenosis, anterior displaced anus)
  • Intestinal nerve or muscle disorders (e.g., Hirschprung disease, visceral myopathies, visceral neuropathies)
  • Neuropathic conditions (e.g., spinal cord abnormalities, neurofibromatosis, tethered cord, spinal cord trauma)
  • Lead toxicity, hypercalcemia
  • Inflammatory bowel disease
  • Lactose intolerance that is associated with symptoms which could confound the assessments in this study
  • History of cancer. (Note: Participants with a history of cancer are allowed provided that the malignancy has been in a complete remission before enrollment/randomization (Visit 3). A complete remission is defined as the disappearance of all signs of cancer in response to treatment)