A 26-Week Study to Evaluate the Efficacy and Safety of Tenapanor in IBS-C

Study Overview
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Brief Summary
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This phase 3, 26-week, randomized, double-blind, placebo-controlled, multi-center study will evaluate the safety and efficacy of one dose of Tenapanor in subjects with constipation-predominant irritable bowel syndrome (IBS-C) as defined by the ROME III criteria and who have active disease as determined after a two-week screening period. Subjects who qualify and are randomized into the study will either receive 50mg BID of Tenapanor (1:1) for a 26 week treatment period.

Detailed Description
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During the 26-week double-blind treatment period, subjects will record daily assessments including: frequency and timing of bowel movements; sensation of complete bowel emptying; consistency of bowel movements; degree of straining, worst abdominal pain, abdominal discomfort, abdominal bloating, abdominal fullness and abdominal cramping; and use and timing of rescue medication. Subjects will also record weekly assessments including: adequate relief of IBS symptoms, degree of relief of IBS symptoms, IBS severity, and constipation severity.

Official Title
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A 26-Week, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Tenapanor for the Treatment of Constipation-Predominant Irritable Bowel Syndrome (IBS-C)

Conditions
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Constipation Predominant Irritable Bowel Syndrome

Intervention / Treatment
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* Drug: Tenapanor
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females aged 18 to 75 years, inclusive Females must be of non-childbearing potential; If of child-bearing potential, must have negative pregnancy test and confirm the use of one of the appropriate means of contraception Males must agree to use appropriate methods of barrier contraception or have documented surgical sterilization Subject meets definition of IBS-C using Rome III Criteria for the Diagnosis of IBS A colonoscopy based on AGA guidelines; every 10 years at ≥50 years old Exclusion Criteria: Functional diarrhea as defined by Rome III criteria IBS with diarrhea (IBS-D), mixed IBS (IBS-M), or unsubtyped IBS as defined by Rome III criteria Diagnosis or treatment of any clinically symptomatic biochemical or structural abnormality of the GI tract within 6 months prior to screening, or active disease within 6 months prior to screening; including but not limited to cancer, inflammatory bowel disease, diverticulitis, duodenal ulcer, erosive esophagitis, gastric ulcer, pancreatitis (within 12 months of screening), cholelithiasis, amyloidosis, ileus, non-controlled GERD, gastrointestinal obstruction or carcinoid syndrome. Potential CNS cause of constipation (e.g., Parkinson's disease, spinal cord injury, or multiple sclerosis) Subject has a history or current evidence of laxative abuse (in the clinical judgment of physician) Hepatic dysfunction (ALT [SGPT] or AST [SGOT] >2.5 times the upper limit of normal) or renal impairment (serum creatinine >2 mg/dL) Any evidence of or treatment of malignancy (other than localized basal cell, squamous cell skin cancer or cancer in situ that has been resected) within the previous year Any surgery on the stomach, small intestine or colon, excluding appendectomy and cholecystectomy (unless within 60 days of screening visit)

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: 50mg BID<br>Tenapanor, 50mg BID (100mg total) | Drug: Tenapanor<br> <br> * Other names: AZD1722;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Overall Response for 6 Out of 12 Weeks | An overall responder is defined as a weekly responder for the first 6/12 weeks where both CSBM and abdominal pain response criteria were met for the week. The CSBM response criteria are defined as an increase of one or more change in average weekly CSBMs from baseline. The definition of a CSBM is as follows: A CSBM is a spontaneous bowel movement (SBM) for which the subject responds yes to the following question; Did you feel like you completely emptied your bowels? The abdominal pain response criterion is defined as a decrease of 30% or more of percent change in average weekly worst abdominal pain from baseline. | First 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Overall Complete Spontaneous Bowel Movement (CSBM) Response for 6 Out of 12 Weeks | An overall CSBM responder is defined as a weekly responder for the first 6/12 weeks. The CSBM response criteria are defined as an increase of one or more change in average weekly CSBMs from baseline. The definition of a CSBM is as follows: A CSBM is a spontaneous bowel movement (SBM) for which the subject responds yes to the following question; Did you feel like you completely emptied your bowels? | First 12 weeks | 
| Percentage of Subjects With Overall Abdominal Pain Response for 6 Out of 12 Weeks | An overall abdominal pain responder is defined as a weekly responder for the first 6/12 weeks. The abdominal pain response criterion is defined as a decrease of 30% or more of percent change in average weekly worst abdominal pain from baseline. | First 12 weeks | 
| Percentage of Subjects With Overall Response for 13 Out of 26 Weeks | An overall responder is defined as a weekly responder for the first 13/26 weeks where both CSBM and abdominal pain response criteria were met for the week. The CSBM response criteria are defined as an increase of one or more change in average weekly CSBMs from baseline. The definition of a CSBM is as follows: A CSBM is a spontaneous bowel movement (SBM) for which the subject responds yes to the following question; Did you feel like you completely emptied your bowels? The abdominal pain response criterion is defined as a decrease of 30% or more of percent change in average weekly worst abdominal pain from baseline. | 26 weeks | 
| Percentage of Subjects With Overall Complete Spontaneous Bowel Movement (CSBM) Response for 13 Out of 26 Weeks | An overall CSBM responder is defined as a weekly responder for the first 13/26 weeks. The CSBM response criteria are defined as an increase of one or more change in average weekly CSBMs from baseline. The definition of a CSBM is as follows: A CSBM is a spontaneous bowel movement (SBM) for which the subject responds yes to the following question; Did you feel like you completely emptied your bowels? | 26 weeks | 
| Percentage of Subjects With Overall Abdominal Pain Response for 13 Out of 26 Weeks | An overall abdominal pain responder is defined as a weekly responder for the first 13/26 weeks. The abdominal pain response criterion is defined as a decrease of 30% or more of percent change in average weekly worst abdominal pain from baseline. | 26 weeks | 
| Percentage of Subjects With Overall Response for 9 Out of 12 Weeks | An overall responder is defined as a weekly responder for the first 9/12 weeks where both CSBM and abdominal pain response criteria were met for the week. The CSBM response criteria are defined as an increase of one or more change in average weekly CSBMs from baseline and a minimum of at least 3 CSBMs that same week. The definition of a CSBM is as follows: A CSBM is a spontaneous bowel movement (SBM) for which the subject responds yes to the following question; Did you feel like you completely emptied your bowels? The abdominal pain response criterion is defined as a decrease of 30% or more of percent change in average weekly worst abdominal pain from baseline. | First 12 weeks | 
| Percentage of Subjects With Overall Complete Spontaneous Bowel Movement (CSBM) Response for 9 Out of 12 Weeks | An overall CSBM responder is defined as a weekly responder for the first 9/12 weeks. The CSBM response criteria are defined as an increase of one or more change in average weekly CSBMs from baseline and a minimum of at least 3 CSBMs that same week. The definition of a CSBM is as follows: A CSBM is a spontaneous bowel movement (SBM) for which the subject responds yes to the following question; Did you feel like you completely emptied your bowels? | First 12 weeks | 
| Percentage of Subjects With Overall Abdominal Pain Response for 9 Out of 12 Weeks | An overall abdominal pain responder is defined as a weekly responder for the first 9/12 weeks. The abdominal pain response criterion is defined as a decrease of 30% or more of percent change in average weekly worst abdominal pain from baseline. | First 12 weeks |