Linaclotide

An SBM is defined as a BM that occurs in the absence of laxative, enema, or suppository use on the calendar day of the BM or the calendar day before the BM. The caregiver/parent/guardian/legally authorized representative (LAR) will complete the electronic diary (eDiary), providing data for the SBM frequency rate up to the last dose date equivalent to the 12-week SBM frequency rate. Baseline values for efficacy endpoints related to daily eDiary responses were derived from the eDiary in the preintervention period, specifically the time period from 14 days before randomization and up to the time of randomization.

An adverse event (AE) is defined as any untoward medical occurrence in a patient/clinical investigation subject administered a pharmaceutical product which doesn't necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.

An SBM is defined as a BM that occurs in the absence of laxative, enema, or suppository use on the calendar day of the bowel movement (BM) or the calendar day before the BM. Assessments of BM characteristics that determine occurrences of SBM (ie, BM frequency and rescue medication use) were measured by using the eDiary completed twice daily (morning and evening) on the eDiary (Electronic Diary) device.

6/12 weeks APS + 2 responder=participant who meets the weekly APS + 2 responder criteria ≥6 of the 12 weeks of the intervention period. Weekly APS +2 responder=participant who has an increase of ≥2 in the SBM weekly rate from baseline, AND a decrease of ≥30% in mean abdominal pain score from baseline, during that study intervention week. Assessments of abdominal pain and BM characteristics that determine occurrences of SBMs were measured by using an eDiary completed twice daily (AM and PM). Assessments of abdominal pain were measured using a 5-point scale where 0=none and 4=a lot. A participant's abdominal pain score=mean of the non-missing abdominal pain scores during the specified period. Responder rate=percentage of participants who were 6/12 weeks APS + 2 responders. A participant had to have ≥4 completed diary days in the analysis week to be considered a responder for that week and was otherwise considered a non-responder for that week.

An SBM is defined as a BM that occurs in the absence of laxative, enema, or suppository use on the calendar day of the BM or the calendar day before the BM. The caregiver/parent/guardian/legally authorized representative (LAR) will complete the electronic diary (eDiary), providing data for the SBM frequency rate up to the last dose date equivalent to the 4-week SBM frequency rate.

The caregiver/parent/guardian/legally authorized representative (LAR) will rate and record in an eDiary the consistency of the stool for each BM using the Bristol Stool Form 7-point scale in which 1=Separate hard lumps, like nuts (hard to pass); 2=Sausage-shaped, but lumpy; 3=Like a sausage but with cracks on its surface; 4=Like a sausage or snake, smooth and soft; 5=Soft blobs with clear cut edges (easy to pass); 6=Fluffy pieces with ragged edges, a mushy stool; and 7=Watery, no solid pieces, entirely liquid.

Straining for each LAR/parent/guardian/caregiver-observed BM the child passes was collected daily in the eDiary device, using a 4-point scale (0 = No, not at all; 1 = Yes, a little; 2 = Yes, a lot; 3 = I don't know) based on two questions (did he/she grunt or make a face like he/she was straining). Lower value represents a better outcome and "I don't know" is considered as a missing response. The subject's average straining score for each caregiver-observed BM was derived based on the average of non-missing responses of the two straining questions. The participant's straining score in the 4-week Study Intervention Period was the average of the non-missing average straining scores from all caregiver-observed SBMs during the 4-week Study Intervention Period. If a subject had no caregiver-observed SBMs at baseline, then the baseline straining score reported by the caregiver was missing and, therefore, that subject was not included in the change from baseline straining analysis.

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study.

A SBM was defined as a bowel movement (BM) that occurred in the absence of laxative, suppository, or enema use on the calendar day of the BM or the calendar day before the BM. Each day the caregiver recorded the number of SBMs in the last 24 hours in an electronic diary (eDiary). The SBM frequency rate (SBMs/week) during the analysis period for each participant was calculated as \[(total number of SBMs in the analysis period/number of days in the analysis period)\*7\]. Baseline value was based on values collected 14 days before randomization up to randomization. Change from Baseline was calculated as the SBM frequency rate during the 4-week treatment period - SBM frequency rate at Baseline. A positive change from Baseline indicates improvement.

The caregiver rated and recorded in an eDiary the consistency of the stool for each bowel movement using the Bristol Stool Form 7-point scale where: 1=Separate hard lumps, like nuts (hard to pass); 2=Sausage-shaped, but lumpy; 3=Like a sausage but with cracks on its surface; 4=Like a sausage or snake, smooth and soft; 5=Soft blobs with clear cut edges (easy to pass); 6=Fluffy pieces with ragged edges, a mushy stool; 7=Watery, no solid pieces. Entirely liquid. Baseline value was based on values collected 14 days before randomization up to randomization. A participant's stool consistency score for the treatment period was the average of the nonmissing consistency scores from the BMs recorded by the caregiver during the 4-week treatment period.

The caregiver rated and recorded in an eDiary the amount of straining they observed when the child passed the BM (1=Not at all; 2=Yes a little; 3=Yes a lot; I don't know). Baseline value was based on values collected 14 days before randomization up to randomization. A participant's straining score for the treatment period was the average of the nonmissing straining scores from the BMs recorded by the caregiver during the 4-week treatment period. A negative change from Baseline indicates improvement.

Each day the caregiver recorded in an eDiary if the child had a bowel movement accident (Yes; No; I don't know). The percentage of days with fecal incontinence for the treatment period was the average of the nonmissing incidences of fecal incontinence recorded by the caregiver during the 4-week treatment period.

An Adverse Event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease. A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that: results in death, is immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, and/or causes a congenital anomaly/birth defect. A TEAE is an AE that begins or worsens after receiving study drug. Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind study intervention.