A 12-Week Study With a 4-Week Randomized Withdrawal Period to Evaluate the Efficacy and Safety of Tenapanor for the Treatment of IBS-C

Phase 3

Completed

Conditions: Constipation Predominant Irritable Bowel Syndrome

Interventions: Drug: Placebo
Drug: Tenapanor

Registration Number: NCT02621892

Lead Sponsor: Ardelyx

Brief Summary: This phase 3, 12-week, randomized, double-blind, placebo-controlled, multi-center study will evaluate the safety and efficacy 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 or placebo BID for 12 week treatment period and then undergo a 4 week placebo controlled randomized withdrawal.

Detailed Description: During the 12-week treatment period, subjects will record daily assessments including: frequency and timing of bowel movements; sensation and complete bowel emptying; consistency of bowel movements; degree of straining, worst abdominal pain, abdominal discomfort, abdominal bloating, abdominal fullness and abdominal cramping. Subjects will also record weekly assessments including: adequate relief of IBS severity, and constipation severity.

At the end of the 12-week treatment period, there will be a 4-week randomized withdrawal period in which subjects who complete the study in Tenapanor group will be randomized to either Tenapanor 50mg BID or placebo BID (1:1) and subjects who complete the study in the placebo group will be assigned to receive Tenapanor 50mg BID.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 606

Inclusion Criteria

18 to 75 years old
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 an appropriate method 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, or the occurrence of any warning signs

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, ischemic colitis or carcinoid syndrome.
Subject has a history or current evidence of laxative abuse (in the clinical judgment of the physician)
Hepatic dysfunction (ALT [SGPT] or AST [SGOT] >2.5 times the upper limit of normal) or renal impairment (serum creatinine > 2mg/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 or cholecystectomy (unless within 60 days of screening visit)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo
50mg BID	Tenapanor	Tenapanor

Primary Outcome Measures

Name	Time	Method
6 of 12 Week Overall Responder Rate	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.

Secondary Outcome Measures

Name	Time	Method
6 of 12 Week Overall Complete Spontaneous Bowel Movement (CSBM)Responder Rate	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?"
9 of 12 Week Overall Responder Rate	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.
6 of 12 Week Overall Abdominal Pain Responder Rate	12 weeks	An overall abdominal pain responder is defined as a weekly responder for the first 6/12. 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.
9 of 12 Week Overall CSBM Responder Rate	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?"
9 of 12 Week Overall Abdominal Pain Responder Rate	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.

Trial Locations

Locations (111): Ardelyx Investigative Site 137
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Norcross, Georgia, United States
Ardelyx Investigative Site 278
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Hagerstown, Maryland, United States
Ardelyx Investigative Site 135
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Boston, Massachusetts, United States
Ardelyx Investigative Site 170
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Great Neck, New York, United States
Ardelyx Investigative Site 174
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Kinston, North Carolina, United States
Ardelyx Investigative Site 281
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North Charleston, South Carolina, United States
Ardelyx Investigative Site 164
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Corpus Christi, Texas, United States
Ardelyx Investigative Site 182
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Las Vegas, Nevada, United States
Ardelyx Investigative Site 103
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Huntsville, Alabama, United States
Ardelyx Investigative Site 145
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Chandler, Arizona, United States
Ardelyx Investigative Site 100
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Huntsville, Alabama, United States
Ardelyx Investigative Site 187
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Tucson, Arizona, United States
Ardelyx Investigative Site 105
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Canoga Park, California, United States
Ardelyx Investigative Site 143
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Chula Vista, California, United States
Ardelyx Investigative Site 147
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Encino, California, United States
Ardelyx Investigative Site 146
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Encino, California, United States
Ardelyx Investigative Site 107
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Lomita, California, United States
Ardelyx Investigative Site 112
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North Hollywood, California, United States
Ardelyx Investigative Site 110
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Northridge, California, United States
Ardelyx Investigative Site 294
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San Diego, California, United States
Ardelyx Investigative Site 108
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Thousand Oaks, California, United States
Ardelyx Investigative Site 136
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Hialeah, Florida, United States
Ardelyx Investigative Site 178
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Cutler Bay, Florida, United States
Ardelyx Investigative Site 131
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Fort Lauderdale, Florida, United States
Ardelyx Investigative Site 127
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Miami Lakes, Florida, United States
Ardelyx Investigative Site 130
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Hialeah, Florida, United States
Ardelyx Investigative Site 287
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Homestead, Florida, United States
Ardelyx Investigative Site 150
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Saint Petersburg, Florida, United States
Ardelyx Investigative Site 138
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Atlanta, Georgia, United States
Ardelyx Investigative Site 254
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West Palm Beach, Florida, United States
Ardelyx Investigative Site 123
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Miami Springs, Florida, United States
Ardelyx Investigative Site 106
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Miami, Florida, United States
Ardelyx Investigative Site 234
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Athens, Georgia, United States
Ardelyx Investigative Site 124
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Snellville, Georgia, United States
Ardelyx Investigative Site 213
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Savannah, Georgia, United States
Ardelyx Investigative Site 148
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Atlanta, Georgia, United States
Ardelyx Investigative Site 157
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Boise, Idaho, United States
Ardelyx Investigative Site 202
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Oak Lawn, Illinois, United States
Ardelyx Investigative Site 188
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Metairie, Louisiana, United States
Ardelyx Investigative Site 259
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Topeka, Kansas, United States
Ardelyx Investigative Site 192
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Crowley, Louisiana, United States
Ardelyx Investigative Site 177
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Monroe, Louisiana, United States
Ardelyx Investigative Site 255
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Towson, Maryland, United States
Ardelyx Investigative Site 267
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Brockton, Massachusetts, United States
Ardelyx Investigative Site 119
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Caro, Michigan, United States
Ardelyx Investigative Site 224
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Saginaw, Michigan, United States
Ardelyx Investigative Site 125
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Belton, Missouri, United States
Ardelyx Investigative Site 156
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Billings, Montana, United States
Ardelyx Investigative Site 275
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Las Vegas, Nevada, United States
Ardelyx Investigative Site 276
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Las Vegas, Nevada, United States
Ardelyx Investigative Site 151
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Brooklyn, New York, United States
Ardelyx Investigative Site 225
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Hartsdale, New York, United States
Ardelyx Investigative Site 206
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New Windsor, New York, United States
Ardelyx Investigative Site 183
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New York, New York, United States
Ardelyx Investigative Site 226
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Asheville, North Carolina, United States
Ardelyx Investigative Site 104
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Greensboro, North Carolina, United States
Ardelyx Investigative Site 166
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Charlotte, North Carolina, United States
Ardelyx Investigative Site 205
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Fayetteville, North Carolina, United States
Ardelyx Investigative Site 172
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Beavercreek, Ohio, United States
Ardelyx Investigative Site 223
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Cincinnati, Ohio, United States
Ardelyx Investigative Site 201
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Cincinnati, Ohio, United States
Ardelyx Investigative Site 139
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Columbus, Ohio, United States
Ardelyx Investigative Site 173
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Dayton, Ohio, United States
Ardelyx Investigative Site 171
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Huber Heights, Ohio, United States
Ardelyx Investigative Site 247
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Springfield, Ohio, United States
Ardelyx Investigative Site 144
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Jenkintown, Pennsylvania, United States
Ardelyx Investigative Site 289
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Mount Pleasant, South Carolina, United States
Ardelyx Investigative Site 184
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Myrtle Beach, South Carolina, United States
Ardelyx Investigative Site 261
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Sioux Falls, South Dakota, United States
Ardelyx Investigative Site 134
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Chattanooga, Tennessee, United States
Ardelyx Investigative Site 121
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Franklin, Tennessee, United States
Ardelyx Investigative Site 133
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Jackson, Tennessee, United States
Ardelyx Investigative Site 189
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Hermitage, Tennessee, United States
Ardelyx Investigative Site 197
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Corsicana, Texas, United States
Ardelyx Investigative Site 185
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Houston, Texas, United States
Ardelyx Investigative Site 109
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Knoxville, Tennessee, United States
Ardelyx Investigative Site 120
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Houston, Texas, United States
Ardelyx Investigative Site 111
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Plano, Texas, United States
Ardelyx Investigative Site 113
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McKinney, Texas, United States
Ardelyx Investigative Site 118
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Plano, Texas, United States
Ardelyx Investigative Site 207
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Sandy, Utah, United States
Ardelyx Investigative Site 231
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Norfolk, Virginia, United States
Ardelyx Investigative Site 101
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San Antonio, Texas, United States
Ardelyx Investigative Site 240
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San Antonio, Texas, United States
Ardelyx Investigative Site 210
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Phoenix, Arizona, United States
Ardelyx Investigative Site 235
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Nashville, Tennessee, United States
Ardelyx Investigative Site 277
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Tempe, Arizona, United States
Ardelyx Investigative Site 269
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Tucson, Arizona, United States
Ardelyx Investigative Site 128
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Chesterfield, Michigan, United States
Ardelyx Investigative Site 159
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Orem, Utah, United States
Ardelyx Investigative Site 149
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Birmingham, Alabama, United States
Ardelyx Investigative Site 114
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Birmingham, Alabama, United States
Ardelyx Investigative Site 162
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Evanston, Illinois, United States
Ardelyx Investigative Site 102
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Blue Island, Illinois, United States
Ardelyx Investigative Site 296
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Phoenix, Arizona, United States
Ardelyx Investigative Site 140
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Harrisburg, Arkansas, United States
Ardelyx Investigative Site 132
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Port Orange, Florida, United States
Ardelyx Investigative Site 126
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Pompano Beach, Florida, United States
Ardelyx Investigative Site 198
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Zachary, Louisiana, United States
Ardelyx Investigative Site 175
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Vineland, New Jersey, United States
Ardelyx Investigative Site 199
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Tucson, Arizona, United States
Ardelyx Investigative Site 274
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Little Rock, Arkansas, United States
Ardelyx Investigative Site 122
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Little Rock, Arkansas, United States
Ardelyx Investigative Site 155
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South Ogden, Utah, United States
Ardelyx Investigative Site 280
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Winston-Salem, North Carolina, United States
Ardelyx Investigative Site 142
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Omaha, Nebraska, United States
Ardelyx Investigative Site 141
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Richmond, Virginia, United States
Ardelyx Investigative Site 117
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Mentor, Ohio, United States
Ardelyx Investigative Site 129
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North Little Rock, Arkansas, United States
Ardelyx Investigative Site 161
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Little Rock, Arkansas, United States
Ardelyx Investigative Site 293
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Albuquerque, New Mexico, United States