Linaclotide Safety and Efficacy in Pediatric Participants, 6 to 17 Years of Age, With Irritable Bowel Syndrome With Constipation (IBS-C) or Functional Constipation (FC)

Inclusion Criteria:

• Male and female participants must be ages 6 to 17 years (FC participants) or ages 7to 17 years (IBS-C participants) (inclusive) at the time the participant providesassent for the study and parent/guardian/legally authorized representative (LAR) hasprovided signed consent;

• Participant weighs ≥18 kg at the time the participant provides assent and theparent/guardian/LAR has provided signed consent;

• Participants who meet the modified Rome III criteria for Child/Adolescent FC. For atleast 2 months before the Screening Visit, the participant has had 2 or fewerdefecations (with each defecation occurring in the absence of any laxative,suppository, or enema use during the preceding 24 hours) in the toilet per week.

In addition, participant meets one or more of the following criteria at least once per week for at least 2 months before the screening visit:

a. History of retentive posturing or excessive volitional stool retention; b. History of painful or hard BMs; c. History of large diameter stools that may obstruct the toilet; d. Presence of a large fecal mass in the rectum; e. At least 1 episode of fecal incontinence per week

• For IBS-C participants only: Participant meets Rome III criteria forchild/adolescent IBS: At least once per week for at least 2 months before theScreening Visit, the participant experienced abdominal discomfort (an uncomfortablesensation not described as pain) or pain associated with 2 or more of the followingat least 25% of the time:

1. Improvement with defecation;

2. Onset associated with a change in frequency of stool;

3. Onset associated with a change in form (appearance) of stool;

• For IBS-C participants only: Participant has an average daytime abdominal pain scoreof ≥ 1 (at least "a tiny bit") during the 14 days before Visit 3;

• Participant is willing to discontinue any laxatives used before the PreinterventionVisit in favor of the protocol- permitted rescue medicine;

• Participant has an average of fewer than 3 SBMs per week during the 14 days beforethe randomization day and up to the randomization (including the morning eDiaryassessments reported before administration of first dose of double-blind studyintervention on the randomization day). An SBM is defined as a BM that occurs in theabsence of laxative, enema, or suppository use on the calendar day of the BM or thecalendar day before the BM;

• Participant or parent/guardian/LAR or caregiver is compliant with eDiaryrequirements by completing both the morning and evening assessments for 10 out ofthe 14 days immediately preceding the Randomization Visit;

• Female participants of childbearing potential must have a negative serum pregnancytest at the Screening Visit and a negative urine pregnancy test at the RandomizationVisit prior to dosing;

• Female participants who have had their first menstrual period and are sexuallyactive must agree to use a reliable form of contraception;

• Participant must provide written or verbal informed assent and theparent/guardian/LAR and caregiver must provide written informed consent before theinitiation of any study-specific procedures;

• Participant is able to read and/or understand the assessments in the eDiary device.If the participant is 6 to 11 years of age (FC participants) or 7 to 11 years of age (IBS-C participants) and does not meet this criterion, the interviewer-administeredversion of the eDiary must be used and the parent/guardian/LAR or caregiver who willbe administering the interviewer-administered version of the eDiary must undergotraining;

• Participant must have acquired toilet training skills.

Exclusion Criteria:

• For FC participants only: Participant meets Rome III criteria for Child/AdolescentIBS: At least once per week for at least 2 months before the Screening Visit, theparticipant has experienced abdominal discomfort (an uncomfortable sensation notdescribed as pain) or pain associated with 2 or more of the following at least 25%of the time:

1. Improvement with defecation

2. Onset associated with a change in frequency of stool

3. Onset associated with a change in form (appearance) of stool;

• Participant reports having more than 1 loose, mushy stool (eDiary-recorded stoolconsistency of 6 on the Pediatric Bristol Stool Form Scale [p-BSFS]) or any waterystool (eDiary-recorded stool consistency of 7 on the p-BSFS) with any SBM thatoccurred in the absence of laxative use on the calendar day of the BM or thecalendar day before the BM during the 14 days before the randomization day and up tothe randomization (including the morning eDiary assessments reported beforeadministration of first dose of double-blind study intervention on the randomizationday);

• Participant has a history of non-retentive fecal incontinence;

• Participant has (a) fecal impaction at Visit 2 after failing outpatient clean-outduring the Screening Period or (b) fecal impaction at Visit 3;

• Participant has required manual disimpaction any time prior to randomization;

• Participant currently has both unexplained and clinically significant alarm symptoms (lower GI bleeding [rectal bleeding or heme-positive stool], iron-deficiency anemia,or any unexplained anemia, or weight loss) and systemic signs of infection orcolitis, or any neoplastic process;

• Participant has clinically significant findings on a physical examination, vitalsign assessment, electrocardiogram (ECG), or clinical laboratory test as determinedby the investigator based on consideration of whether the finding could represent asafety concern or a condition that would be exclusionary, could prevent theparticipant from performing any protocol assessments, or could confound studyassessments;

• Participant has a history of drug or alcohol abuse;

• Participant has any of the following conditions:

1. Celiac disease, or positive serological test for celiac disease and thecondition has not been ruled out by endoscopic biopsy;

2. Cystic fibrosis;

3. Hypothyroidism that is untreated or treated with thyroid hormone at a dose thathas not been stable for at least 3 months prior to the Screening Visit;

4. Down's syndrome or any other chromosomal disorder;

5. Active anal fissure (Note: History of anal fissure is not an exclusion);

6. Anatomic malformations (eg, imperforate anus, anal stenosis, anterior displacedanus);

7. Intestinal nerve or muscle disorders (eg, Hirschprung disease, visceralmyopathies, visceral neuropathies);

8. Neuropathic conditions (eg, spinal cord abnormalities, neurofibromatosis,tethered cord, spinal cord trauma);

9. Lead toxicity, hypercalcemia;

10. Neurodevelopmental disabilities (early-onset, chronic disorders that share theessential feature of a predominant disturbance in the acquisition of cognitive,motor, language, or social skills, which has a significant and continuingimpact on the developmental progress of an individual) producing a cognitivedelay that precludes comprehension and completion of the daily eDiary (Electronic handheld device) or other study-related questionnaires (Note:Participants are excluded if the person who will be completing the daily eDiaryor other study-related questionnaires meets this criterion);

11. Inflammatory bowel disease;

12. Childhood functional abdominal pain syndrome;

13. Childhood functional abdominal pain;

14. Poorly treated or poorly controlled psychiatric disorders that might influencehis or her ability to participate in the study;

15. Lactose intolerance that is associated with abdominal pain or discomfort andcould confound the assessments in this study;

16. History of cancer other than treated basal cell carcinoma of the skin; (Note:Participants with a history of cancer are allowed provided that the malignancyhas been in a complete remission for at least 5 years before the RandomizationVisit. A complete remission is defined as the disappearance of all signs ofcancer in response to treatment);

17. History of diabetic neuropathy.

• Participant has an acute or chronic condition that, in the investigator's opinion,would limit the participants' ability to complete or participate in this clinicalstudy;

• Participant has a known or suspected mechanical bowel obstruction orpseudoobstruction;

• Participant has a known allergy or sensitivity to the study intervention or itscomponents or other medications in the same drug class.

• Participant has had surgery that meets any of the following criteria:

1. Bariatric surgery for treatment of obesity, or surgery to remove a segment ofthe GI tract at any time before the Screening Visit;

2. Surgery of the abdomen, pelvis, or retroperitoneal structures during the 6months before the Screening Visit;

3. An appendectomy or cholecystectomy during the 60 days before the ScreeningVisit;

4. Other major surgery during the 30 days before the Screening Visit;

• Participant used a protocol-specified prohibited medicine before the start of thePreintervention Period or failed to meet the stable-dose requirements of certainmedications;

• Participant used rescue medication on the calendar day before the RandomizationVisit and on the day of the Randomization Visit until randomized;

• Participant received a study intervention during the 30 days before the ScreeningVisit or is planning to receive a study intervention (other than that administeredduring this study);

• Participant has been randomized into any clinical study in which linaclotide was astudy intervention.

• The participant has a condition or is in a situation; which, in the investigator'sopinion, may put the participant at significant risk, may confound the study results ,or may interfere significantly with the participant's participation in the study;

• Participants who have positive urine drug screen results for cocaine, barbiturates,opiates, or cannabinoids will be excluded from study participation;

• Female participants who are currently pregnant or nursing, or plan to becomepregnant or nurse during the clinical study;

• Participant's parent/guardian/LAR or caregiver has been directly or indirectlyinvolved in the conduct and administration of this study as an investigator, studycoordinator, or other study staff member. In addition, any participant,parent/guardian/LAR or caregiver who has a first-degree family member, significantother, or relative residing with him/her directly or indirectly who is involved inthis study.