An Efficacy and Safety Study of Plecanatide in Adolescents 12 to <18 Years of Age With Chronic Idiopathic Constipation

Study Overview
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Brief Summary
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This is a study of efficacy and safety of Plecanatide in pediatric subjects aged 12 to < 18 years diagnosed with Chronic Idiopathic Constipation.

Detailed Description
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The purpose of the study is to evaluate efficacy, safety, and pharmacokinetics (PK) of oral Plecanatide 0.5, 1.0 and 1.5 mg tablets dosed once a day as compared to matching placebo, when administered for 8 weeks in adolescents with chronic idiopathic constipation. This study will consist of a 4-week screening period, 8 weeks of treatment, and a 2-week follow-up. The study will assess the effects of Plecanatide on bowel movement frequency and other clinical features of CIC.

Official Title
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A Randomized, Double-blind, Placebo-controlled, 3 Dose Level, Parallel Group Study of the Efficacy and Safety of Plecanatide in Adolescents 12 to < 18 Years of Age With Chronic Idiopathic Constipation (CIC)

Conditions
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Chronic Idiopathic Constipation

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female adolescents 12 to less than 18 years of age. Diagnosed with CIC based on the Rome III criteria for child/adolescent functional constipation (Appendix A). Patient is able to voluntarily provide written, signed, and dated (personally and via a legally authorized representative [LAR]) assent/informed consent as applicable to participate in the study. Subject's parent/LAR demonstrates an understanding, ability, and willingness to fully comply with study procedures (e.g., accept venipuncture, willing and able to swallow tablets, accept urine drug screen for opiates) and restrictions. Key Exclusion 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 currently requires iron supplements, amitriptyline, or other tricyclic antidepressants for depression, opioid-containing medications or compounds for pain, or has other conditions that require medications known to cause constipation. A patient with an onset of constipation prior to the use of these medications and who has been on a stable dose for at least 8 weeks prior to Screening might be considered eligible for this study if the investigator deems these medications do not significantly contribute to the patient's constipation. Screening of these patients needs to be approved by the medical monitor and the sponsor. The patient, if female of childbearing potential (defined as postmenarche), does not agree to practice 1 of the following medically acceptable methods of birth control throughout the study: Hormonal methods such as oral, implantable, injectable, vaginal ring, or transdermal contraceptives for a minimum of 1 full cycle (based on the patient's usual menstrual cycle period) before study drug administration. Total abstinence from sexual intercourse since the last menses before study drug administration. Intrauterine device. Double barrier method (condoms, sponge, or diaphragm with spermicidal jellies or cream. The patient follows a diet not considered normal by the investigator for the patient's age, relative to variety of food, caloric content, and quantity. The patient must have been on a stable diet for at least 30 days weeks prior to Screening. The patient's mobility or normal exercise tolerance is compromised in the investigator's opinion. The patient has a history of an eating disorder.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Plecanatide 0.5 mg<br>Taken orally once daily in the morning for 8 weeks | Drug: Plecanatide<br> <br> * Other names: Trulance;|
| Experimental: Plecanatide 1.0 mg<br>Taken orally once daily in the morning for 8 weeks | Drug: Plecanatide<br> <br> * Other names: Trulance;|
| Experimental: Plecanatide 1.5 mg<br>Taken orally once daily in the morning for 8 weeks | Drug: Plecanatide<br> <br> * Other names: Trulance;|
| Placebo Comparator: Matching placebo<br>Taken orally once daily in the morning for 8 weeks | Drug: Matching placebo<br> <br> * Other names: No other names;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Overall Responders | An Overall Responder is a participant who was a Spontaneous Bowel Movement (SBM) responder for the last 2 weeks of the Treatment Period. An SBM responder is defined as a participant who had >3 SBMs per week. SBM was defined as a bowel movement that occurs in the absence of laxative use within the preceding 24 hours. Participants missing with respect to the outcome measure were scored as non-responders. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Weekly Average Stool Consistency Bristol Stool Form Scale (BSFS) Score | Stool consistency was assessed via the 7-point (1-7) Bristol Stool Form Scale (BSFS) and recorded in the bowel movement (BM) and Symptom Diaries. Lower numbers represent more formed stools; higher numbers represent less formed stools. The weekly mean BSFS score per patient = (total of all BSFS scores reported for a corresponding Spontaneous Bowel Movement (SBM) per time period)/n, where n = number of SBMs scored during the time period. Baseline was the mean BSFS score recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. BSFS types were 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 (passed easily); 6) fluffy pieces with ragged edges, a mushy stool; 7) watery, no solid pieces, entirely liquid. | 8 weeks | 
| Change From Baseline in the Weekly Rate of Spontaneous Bowel Movements (SBM) | The weekly Spontaneous Bowel Movement (SBM) totals were derived from the daily diary entries reported during the Treatment Period in the Bowel Movement (BM) and symptom diaries. Baseline was the mean number of SBMs recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. SBM is defined as a bowel movement that occurs in the absence of laxative use within the preceding 24 hours | 8 weeks | 
| Change From Baseline in the Weekly Rate of Complete Spontaneous Bowel Movements (CSBM) | The weekly Complete Spontaneous Bowel Movement (CSBM) totals are derived from the daily diary entries reported during the Treatment Period in the Bowel Movement (BM) and symptom diaries. Baseline is the mean number of CSBMs recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. Spontaneous Bowel Movement (SBM) was defined as a bowel movement that occurs in the absence of laxative use within the preceding 24 hours. CSBM was defined as a spontaneous bowel movement with the sense of complete evacuation. | 8 weeks |