The Plecanatide Chronic Idiopathic Constipation (CIC) Study

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo controlled, 12 week repeat oral dose, dose ranging study to determine the efficacy and safety of 3 doses of plecanatide compared to placebo in patients with Chronic Idiopathic Constipation (CIC).

Detailed Description
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This is a Phase IIb/III, randomized, double-blind, placebo-controlled, 12-Week, Repeat, Oral Dose Ranging, study to determine the safety and efficacy of plecanatide in patients with chronic idiopathic constipation (CIC). Subjects diagnosed with CIC via modified Rome III criteria will be screened against the inclusion and exclusion criteria for the study and enter a 2 Week pre treatment screening. During this phase patients will be required to call in their bowel movements (BM diary) as they occur, and call at least once daily to complete a patient diary of questions on their symptoms (Symptom Diary) associated with CC, as they will throughout the trial. Patients who complete at least 5 days of dosing per week, 6 of each 7 day period of BM diary calls, and continue to have less than 3 complete spontaneous movements per week (as well as meeting other inclusion and exclusion criteria) will be enrolled and randomized to one of three plecanatide doses 0.3 mg, 1.0 mg, and 3.0 mg or placebo. 880 patients will be randomized with the intent of having 200 patients per treatment group (each group the same size) included in efficacy analyses. All subjects receiving at least one dose of plecanatide or matching placebo will be included in the safety analyses.

Official Title
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Study SP304-20210: A Randomized, 12-Week, Double-Blind, Placebo-Controlled, Repeat-Dose, Oral, Dose-Ranging Study to Assess the Safety and Efficacy of Plecanatide in Patients With Chronic Idiopathic Constipation

Conditions
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Chronic Idiopathic Constipation

Intervention / Treatment
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* Drug: plecanatide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18-75, inclusive Body Mass Index = 18-35 kg/m2, inclusive Meets modified Rome III criteria for functional chronic idiopathic constipation for at least 3 months with symptom onset for at least 6 months. Note: For this trial, patients with manual maneuvers required for >25% of defecations will not be eligible for participation. Less than 3 CSBMs per week at baseline and during pretreatment Completed a colonoscopy in accordance with medical guidelines as appropriate, with no clinically significant findings Patient is willing to discontinue use of supplemental fiber, laxatives, prescription and nonprescription medications, herbal or dietary supplements intended to treat constipation during the screening, pre-treatment, treatment and 2-week post-treatment periods Willing to maintain a stable diet during the study. Patients with hemorrhoids and/or diverticulosis (NOT diverticulitis) CAN be entered into the study. Exclusion Criteria: Loose stool (mushy) or watery (Bristol score- 6 or 7) stool in the absence of any laxative or prohibited medicine for > 25% of BMs during the 3 months prior to screening visit OR during the 14 day treatment period Patient meets the Rome III criteria for Irritable Bowel Syndrome (IBS-C) Active peptic ulcer disease not adequately treated or not stable History of cathartic colon, laxative, enema abuse, or ischemic colitis. Fecal impaction within 3 months of screening Patient has had /has any: diseases or conditions associated with constipation (GI or CNS), structural abnormality of the GI tract or gastric bypass surgery, pelvic floor dysfunction, pseudo-obstruction, active infectious gastritis, diverticulitis, anal fissures or any disease or condition that can affect GI motility or defecation or can be associated with abdominal pain Unexplained and clinically significant alarm symptoms including lower GI bleeding, iron-deficiency anemia, weight loss or systemic signs of infection or colitis. Major surgery within 60 days of screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 0.3 mg<br>Subjects receive plecanatide 0.3 mg for 12 consecutive weeks | Drug: plecanatide<br>* Subjects receive experimental study drug for 12 weeks.<br>* Other names: Trulance;|
| Experimental: plecanatide 1.0 mg<br>Subjects receive plecanatide 1.0 mg for 12 consecutive weeks | Drug: plecanatide<br>* Subjects receive experimental study drug for 12 weeks.<br>* Other names: Trulance;|
| Experimental: plecanatide 3.0 mg<br>Subjects receive plecanatide 3.0 mg for 12 consecutive weeks | Drug: plecanatide<br>* Subjects receive experimental study drug for 12 weeks.<br>* Other names: Trulance;|
| Placebo Comparator: Placebo<br>Subjects receive placebo for 12 consecutive weeks | Other: Placebo<br>* Subjects receive experimental study drug for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Responder 9/12 Weeks | A Complete Spontaneous Bowel Movement (CSBM) is a Bowel Movement (BM) that occurs in the absence of laxative use within 24 hours of the BM and the patient reports a feeling of complete evacuation. A weekly responder will have 3 or more CSBMs and an increase of at least one CSBM from baseline in the same week. An overall responder is a patient who is a weekly responder for at least 9 of the 12 treatment weeks, including at least 3 of the last 4 weeks. | 12-Week Treatment Period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 12-week CSBM Weekly Frequency Rate | The number of Complete Spontaneous Bowel Movements (CSBMs) per week | 12-Week Treatment Period | 
| Change From Baseline in 12-week SBM Weekly Frequency Rate | The number of Spontaneous Bowl Movements experienced per week. | 12-Week Treatment Period | 
| Change From Baseline in Stool Consistency (BSFS) to Over Treatment Period | The stool consistency of each bowel movement (BM) was assessed by patients using the 7-point Bristol Stool Form Scale [BSFS] from 1 to 7. = separate hard lumps like nuts (difficult to pass) = sausage shaped but lumpy = like a sausage but with cracks on its surface = like a sausage or snake, smooth and soft = soft blobs with clear-cut edges (passed easily) = fluffy pieces with ragged edges, a mushy stool = watery, no solid pieces (entirely liquid) | 12-Week Treatment Period | 
| Change From Baseline in 12-week Patient Reported Symptoms Associated With Constipation - Straining Score | The severity of straining (Straining Score) was reported by the patients using a 11-point scale (0-10) where 0 = none and 10 = the worst | 12-Week Treatment Period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Idiopathic Constipation, Constipation, Sign and Symptoms: Digestive