12-Week Study of Plecanatide for CIC (The National CIC3 Study)

Study Overview
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Brief Summary
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The purpose of this study is to confirm that the investigational medication, plecanatide, is safe and effective in treating chronic idiopathic constipation.

Detailed Description
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This is a national, randomized, 12-week, double-blind, placebo-controlled, study in approximately 1350 adult male and female patients with CIC comparing 2 doses of plecanatide to placebo. The study will be conducted at approximately 180 clinical study sites in the United States. The primary objective of the study is to evaluate the efficacy and safety of 3.0 and 6.0 mg of plecanatide administered once daily (QD) for 12 weeks in a population of patients with CIC. The study population will include only patients without other causes of constipation or other chronic conditions that could interfere with study assessments. Patients may not take laxatives (with the exception of the study-provided rescue medication, bisacodyl 5mg tablets), or a number of prohibited drugs that are known to cause constipation or diarrhea, during study participation. There are 6 scheduled study visits, including the screening and follow-up visits. The planned duration of participation in this study will be 112 days and up to 155 days, with washout and all visit windows considered.

Official Title
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A National, Randomized, 12-Week, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Plecanatide (3.0 and 6.0 mg) in Patients With Chronic Idiopathic Constipation

Conditions
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Chronic Idiopathic Constipation

Intervention / Treatment
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* Drug: Plecanatide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18-80, inclusive Meets modified Rome III criteria for functional chronic idiopathic constipation for at least 3 months with symptom onset for at least 6 months Completed a colonoscopy in accordance with American Gastroenterological Association (AGA) colon cancer screening guidelines (5 years), with no clinically significant findings Willing to maintain a stable diet during 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 Bowel Movements (BMs) during the 3 months prior to screening visit OR during the 14 day pre-treatment assessment Active peptic ulcer disease, diabetes or hypertension 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, stroke or myocardial infarction (MI) within 60 days of screening Participated in a previous plecanatide clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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 3.0 mg<br>Plecanatide tablets 3.0 mg QD for 12 weeks | Drug: Plecanatide<br> <br> |
| Placebo Comparator: Placebo<br>Matching placebo tablets QD for 12 weeks | Drug: Placebo<br> <br> |
| Experimental: Plecanatide 6.0 mg<br>Plecanatide tablets 6.0 mg QD for 12 weeks | Drug: Plecanatide<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Durable Overall CSBM Responders, Mean Replacement Approach | The primary efficacy endpoint was measured by the number of durable overall CSBM responders over the 12-week Treatment Period. A durable overall CSBM responder was defined as a weekly CSBM responder for at least 9 of the 12 treatment weeks, including at least 3 of the last 4 weeks. A CSBM weekly responder was defined as a patient who has ≥ 3 Complete Spontaneous Bowel Movements (CSBMs) per week and an increase from baseline of ≥1 CSBM for that week. A CSBM was a bowel movement that occurred in the absence of laxative use within 24 hours and was associated with the feeling of complete evacuation. | 12-Week Treatment Period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in CSBMs (CSBMs/Week) Over the 12-week Treatment Period , Mean Replacement Approach | The change from baseline in the number of Complete Spontaneous Bowel Movements (CSBMs) over the 12-week Treatment Period was analyzed. Baseline was the mean number of CSBMs recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. A CSBM was a bowel movement that occurred in the absence of laxative use within 24 hours and was associated with the feeling of complete evacuation. | Baseline and 12 weeks | 
| Change From Baseline in SBMs (SBMs/Week) Over the 12-week Treatment Period, Mean Replacement Approach | The change from baseline in the number of Spontaneous Bowel Movement (SBM) over the 12-week Treatment Period was analyzed. Baseline was the mean number of SBMs recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. The weekly SBM totals were derived from the daily diary entries reported during the Treatment Period. | Baseline and 12 weeks | 
| Change From Baseline in Average Weekly SBM Stool Consistency Over the 12-week Treatment Period, Mean Replacement Approach | The change from baseline in the stool consistency score (i.e. BSFS) over the 12-week Treatment Period was analyzed. Baseline was the mean BSFS score recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. The weekly mean BSFS score per patient was derived from the BSFS entries reported during the Treatment Period in the Daily Symptom Diary. 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) | Baseline and 12 weeks | 
| Change From Baseline in Average Weekly Straining Score Over the 12-week Treatment Period, Mean Replacement Approach | The change from baseline in the straining score over the 12-week Treatment Period was analyzed. Baseline was the mean of non-missing straining scores recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. The weekly average straining score was derived from the straining scores reported during the Treatment Period in the Daily Symptom Diary. The severity of straining during bowel movements was assessed on a 5-point Likert scale where 0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe. | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CIC, Constipation, Chronic Constipation, Synergy, Plecanatide