MedPath

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

Phase 3
Completed
Conditions
Constipation Predominant Irritable Bowel Syndrome
Interventions
Drug: Placebo
Drug: Tenapanor
Registration Number
NCT02686138
Lead Sponsor
Ardelyx
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
593
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
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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)
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo
50mg BIDTenapanorTenapanor, 50mg BID (100mg total)
Primary Outcome Measures
NameTimeMethod
Percentage of Subjects With Overall Response for 6 Out of 12 WeeksFirst 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
NameTimeMethod
Percentage of Subjects With Overall Complete Spontaneous Bowel Movement (CSBM) Response for 6 Out of 12 WeeksFirst 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?"

Percentage of Subjects With Overall Abdominal Pain Response for 6 Out of 12 WeeksFirst 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.

Percentage of Subjects With Overall Complete Spontaneous Bowel Movement (CSBM) Response for 13 Out of 26 Weeks26 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?"

Percentage of Subjects With Overall Response for 13 Out of 26 Weeks26 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.

Percentage of Subjects With Overall Abdominal Pain Response for 13 Out of 26 Weeks26 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.

Percentage of Subjects With Overall Response for 9 Out of 12 WeeksFirst 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.

Percentage of Subjects With Overall Complete Spontaneous Bowel Movement (CSBM) Response for 9 Out of 12 WeeksFirst 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?"

Percentage of Subjects With Overall Abdominal Pain Response for 9 Out of 12 WeeksFirst 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 (116)

Ardelyx Investigative Site 257

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Dothan, Alabama, United States

Ardelyx Investigative Site 288

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Miami, Florida, United States

Ardelyx Investigative Site 138

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Atlanta, Georgia, United States

Ardelyx Investigative Site 253

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Atlanta, Georgia, United States

Ardelyx Investigative Site 182

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Las Vegas, Nevada, United States

Ardelyx Investigative Site 286

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Houston, Texas, United States

Ardelyx Investigative Site 204

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Cincinnati, Ohio, United States

Ardelyx Investigative Site 201

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Cincinnati, Ohio, United States

Ardelyx Investigative Site 235

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Nashville, Tennessee, United States

Ardelyx Investigative Site 186

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San Antonio, Texas, United States

Ardelyx Investigative Site 167

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Salt Lake City, Utah, United States

Ardelyx Investigative Site 210

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Phoenix, Arizona, United States

Ardelyx Investigative Site 236

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Oklahoma City, Oklahoma, United States

Ardelyx Investigative Site 292

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Conway, Arkansas, United States

Ardelyx Investigative Site 189

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Hermitage, Tennessee, United States

Ardelyx Investigative Site 214

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Marrero, Louisiana, United States

Ardelyx Investigative Site 154

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Metairie, Louisiana, United States

Ardelyx Investigative Site 109

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Knoxville, Tennessee, United States

Ardelyx Investigative Site 271

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Bangor, Maine, United States

Ardelyx Investigative Site 122

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Little Rock, Arkansas, United States

Ardelyx Investigative Site 175

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Vineland, New Jersey, United States

Ardelyx Investigative Site 212

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Bristol, Connecticut, United States

Ardelyx Investigative Site 221

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Biloxi, Mississippi, United States

Ardelyx Investigative Site 266

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Memphis, Tennessee, United States

Ardelyx Investigative Site 143

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Chula Vista, California, United States

Ardelyx Investigative Site 256

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Tucson, Arizona, United States

Ardelyx Investigative Site 209

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Saraland, Alabama, United States

Ardelyx Investigative Site 100

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Huntsville, Alabama, United States

Ardelyx Investigative Site 296

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Phoenix, Arizona, United States

Ardelyx Investigative Site 103

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Huntsville, Alabama, United States

Ardelyx Investigative Site 200

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Foley, Alabama, United States

Ardelyx Investigative Site 269

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Tucson, Arizona, United States

Ardelyx Investigative Site 106

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Miami, Florida, United States

Ardelyx Investigative Site 284

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La Mirada, California, United States

Ardelyx Investigative Site 191

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Lynn Haven, Florida, United States

Ardelyx Investigative Site 233

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Wheat Ridge, Colorado, United States

Ardelyx Investigative Site 136

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Hialeah, Florida, United States

Ardelyx Investigative Site 130

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Hialeah, Florida, United States

Ardelyx Investigative Site 250

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Marietta, Georgia, United States

Ardelyx Investigative Site 254

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West Palm Beach, Florida, United States

Ardelyx Investigative Site 137

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Norcross, Georgia, United States

Ardelyx Investigative Site 148

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Atlanta, Georgia, United States

Ardelyx Investigative Site 272

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Decatur, Georgia, United States

Ardelyx Investigative Site 158

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Madisonville, Kentucky, United States

Ardelyx Investigative Site 227

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Evergreen Park, Illinois, United States

Ardelyx Investigative Site 195

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Morgantown, West Virginia, United States

Ardelyx Investigative Site 218

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Evansville, Indiana, United States

Ardelyx Investigative Site 291

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Hoffman Estates, Illinois, United States

Ardelyx Investigative Site 160

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Annapolis, Maryland, United States

Ardelyx Investigative Site 283

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Buckley, Michigan, United States

Ardelyx Investigative Site 203

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New Hyde Park, New York, United States

Ardelyx Investigative Site 170

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Great Neck, New York, United States

Ardelyx Investigative Site 282

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Jefferson City, Missouri, United States

Ardelyx Investigative Site 202

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Oak Lawn, Illinois, United States

Ardelyx Investigative Site 270

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Mandeville, Louisiana, United States

Ardelyx Investigative Site 239

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Flint, Michigan, United States

Ardelyx Investigative Site 168

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Troy, Michigan, United States

Ardelyx Investigative Site 205

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Fayetteville, North Carolina, United States

Ardelyx Investigative Site 230

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Brooklyn, New York, United States

Ardelyx Investigative Site 156

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Billings, Montana, United States

Ardelyx Investigative Site 219

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Lima, Ohio, United States

Ardelyx Investigative Site 171

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Huber Heights, Ohio, United States

Ardelyx Investigative Site 190

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Greensboro, North Carolina, United States

Ardelyx Investigative Site 173

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Dayton, Ohio, United States

Ardelyx Investigative Site 232

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Wadsworth, Ohio, United States

Ardelyx Investigative Site 262

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Houston, Texas, United States

Ardelyx Investigative Site 246

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Rapid City, South Dakota, United States

Ardelyx Investigative Site 265

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Gaffney, South Carolina, United States

Ardelyx Investigative Site 252

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Columbia, South Carolina, United States

Ardelyx Investigative Site 208

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Franklin, Ohio, United States

Ardelyx Investigative Site 217

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Chattanooga, Tennessee, United States

Ardelyx Investigative Site 220

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Levittown, Pennsylvania, United States

Ardelyx Investigative Site 121

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Franklin, Tennessee, United States

Ardelyx Investigative Site 279

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Spring Hill, Tennessee, United States

Ardelyx Investigative Site 180

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Channelview, Texas, United States

Ardelyx Investigative Site 181

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San Antonio, Texas, United States

Ardelyx Investigative Site 242

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Spokane, Washington, United States

Ardelyx Investigative Site 249

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Norfolk, Virginia, United States

Ardelyx Investigative Site 258

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Petersburg, Virginia, United States

Ardelyx Investigative Site 290

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Tampa, Florida, United States

Ardelyx Investigative Site 285

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Wilmington, North Carolina, United States

Ardelyx Investigative Site 268

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Burr Ridge, Illinois, United States

Ardelyx Investigative Site 124

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Snellville, Georgia, United States

Ardelyx Investigative Site 229

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Decatur, Georgia, United States

Ardelyx Investigative Site 267

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Brockton, Massachusetts, United States

Ardelyx Investigative Site 248

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East Providence, Rhode Island, United States

Ardelyx Investigative Site 113

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McKinney, Texas, United States

Ardelyx Investigative Site 231

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Norfolk, Virginia, United States

Ardelyx Investigative Site 263

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Port Arthur, Texas, United States

Ardelyx Investigative Site 245

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Virginia Beach, Virginia, United States

Ardelyx Investigative Site 213

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Savannah, Georgia, United States

Ardelyx Investigative Site 147

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Encino, California, United States

Ardelyx Investigative Site 163

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Anaheim, California, United States

Ardelyx Investigative Site 105

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Canoga Park, California, United States

Ardelyx Investigative Site 297

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La Mesa, California, United States

Ardelyx Investigative Site 165

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Long Beach, California, United States

Ardelyx Investigative Site 107

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Lomita, California, United States

Ardelyx Investigative Site 211

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Orange, California, United States

Ardelyx Investigative Site 176

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Brandon, Florida, United States

Ardelyx Investigative Site 178

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Cutler Bay, Florida, United States

Ardelyx Investigative Site 127

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Miami Lakes, Florida, United States

Ardelyx Investigative Site 255

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Towson, Maryland, United States

Ardelyx Investigative Site 228

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Saint Louis, Missouri, United States

Ardelyx Investigative Site 216

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Wyoming, Michigan, United States

Ardelyx Investigative Site 273

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Tulsa, Oklahoma, United States

Ardelyx Investigative Site 185

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Houston, Texas, United States

Ardelyx Investigative Site 179

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Orlando, Florida, United States

Ardelyx Investigative Site 260

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Ann Arbor, Michigan, United States

Ardelyx Investigative Site 222

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Albuquerque, New Mexico, United States

Ardelyx Investigative Site 264

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Albuquerque, New Mexico, United States

Ardelyx Investigative Site 194

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Hickory, North Carolina, United States

Ardelyx Investigative Site 133

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Jackson, Tennessee, United States

Ardelyx Investigative Site 244

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Huntsville, Alabama, United States

Ardelyx Investigative Site 251

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Huntsville, Alabama, United States

Ardelyx Investigative Site 172

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Beavercreek, Ohio, United States

Ardelyx Investigative Site 261

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Sioux Falls, South Dakota, United States

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