Efficacy and Safety of Plecanatide in Children 6 to <18 Years of Age With Irritable Bowel Syndrome With Constipation (IBS-C)

Study Overview
=================
Brief Summary
-----------------
This study of the efficacy and safety of Plecanatide in children 6 to <18 Years of Age with Irritable Bowel Syndrome with Constipation (IBS-C)

Detailed Description
-----------------
The purpose of this study is to evaluate the safety, efficacy and pharmacokinetic (PK) parameters of plecanatide of once daily oral 4 dose levels of plecanatide (0.5, 1.0, 2.0, or 3.0 mg) for 4 weeks as treatment in children 6 to <18 years of age with IBS-C. The study will include a 28-day Screening/Baseline Period, a 4 week treatment period, and a 2-week post-treatment follow-up period. Patients/caregivers will visit the clinic 4 times during the study.

Official Title
-----------------
A Randomized, Double-blind, Placebo-Controlled, Dose Ranging, Parallel-Group Study of the Efficacy and Safety of Plecanatide in Children 6 to <18 Years of Age With Irritable Bowel Syndrome With Constipation (IBS-C)

Conditions
-----------------
Irritable Bowel Syndrome With Constipation

Intervention / Treatment
-----------------
* Drug: Plecanatide
* Drug: Matching placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITERIA A patient will be eligible for study participation if he or she meets all of the following criteria: Male or female child aged 6 to < 18; Meets ROME IV criteria for child/adolescent IBS-C Patient's parent/guardian/LAR is able to voluntarily provide written, signed, and dated consent and patient is able to voluntarily provide assent as per IRB guidance; Patient and patient's parent/guardian/LAR demonstrates an understanding, ability, and willingness to fully comply with study procedures EXCLUSION CRITERIA A patient will be excluded from the study if he or she meets any of the following criteria: The patient has a mental age <4 years in the investigator's opinion; The patient has previously been diagnosed with anorectal malformations, neurological deficits, or anatomical anomalies that would constitute a predisposition to constipation; The patient is pregnant or lactating; The patient's mobility or normal exercise tolerance is compromised in the investigator's opinion; The patient has been screened for or participated in another Synergy study in the past; The patient has a sibling that is currently participating or has participated in another Synergy study.

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.5 mg plecanatide<br>Plecanatide 0.5 mg Taken orally once daily for 4 weeks Group A: 6 to 11 years old | Drug: Plecanatide<br>* Taken orally daily for 4 weeks<br>* Other names: Trulance;|
| Experimental: 1.0 mg plecanatide<br>Plecanatide 1.0 mg Taken orally daily for 4 weeks Group A: 6 to 11 years old Group B: 12 to < 18 years old | Drug: Plecanatide<br>* Taken orally daily for 4 weeks<br>* Other names: Trulance;|
| Experimental: 2.0 mg plecanatide<br>Plecanatide 2.0 mg Taken orally daily for 4 weeks Group B: 12 to < 18 years old | Drug: Plecanatide<br>* Taken orally daily for 4 weeks<br>* Other names: Trulance;|
| Experimental: 3.0 mg plecanatide<br>Plecanatide 3.0 mg Taken orally daily for 4 weeks Group B: 12 to < 18 years old | Drug: Plecanatide<br>* Taken orally daily for 4 weeks<br>* Other names: Trulance;|
| Placebo Comparator: Matching placebo<br>Matching placebo Taken orally daily for 4 weeks Group A: 6 to 11 years old Group B: 12 to < 18 years old | Drug: Matching placebo<br>* Taken orally daily for 4 weeks<br>* Other names: No other names;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in weekly SBM frequency over the 4 Week Treatment Period compared to placebo and across treatment groups |  | 4 Week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in frequency and severity of abdominal pain/discomfort |  | 4 Week | 
| Change from baseline in frequency of BMs and CSBMs |  | 4 Week | 
| Change from baseline in stool consistency (BSFS or mBSFS-C) |  | 4 Week |