Clinical trial NCT02621892: 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
Official title: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Study With a 4-Week Randomized Withdrawal Period to Evaluate the Efficacy and Safety of Tenapanor for the Treatment of Constipation-Predominant Irritable Bowel Syndrome (IBS-C)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Constipation Predominant Irritable Bowel Syndrome
Lead sponsor: Ardelyx
Sponsor class: INDUSTRY
First posted: 2015-12-04
Enrollment: 606
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: 6 of 12 Week Overall Responder Rate
timeFrame: 12 weeks
Secondary outcomes:
measure: 6 of 12 Week Overall Complete Spontaneous Bowel Movement (CSBM)Responder Rate
timeFrame: 12 weeks
measure: 6 of 12 Week Overall Abdominal Pain Responder Rate
timeFrame: 12 weeks
measure: 9 of 12 Week Overall Responder Rate
timeFrame: 12 weeks
measure: 9 of 12 Week Overall CSBM Responder Rate
timeFrame: 12 weeks
measure: 9 of 12 Week Overall Abdominal Pain Responder Rate
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Ardelyx Investigative Site 149
state: Alabama
city: Birmingham
country: United States
facility: Ardelyx Investigative Site 114
state: Alabama
city: Huntsville
country: United States
facility: Ardelyx Investigative Site 103
state: Alabama
city: Huntsville
country: United States
facility: Ardelyx Investigative Site 100
state: Alabama
city: Chandler
country: United States
facility: Ardelyx Investigative Site 145
state: Arizona
city: Phoenix
country: United States
facility: Ardelyx Investigative Site 210
state: Arizona
city: Phoenix
country: United States
facility: Ardelyx Investigative Site 296
state: Arizona
city: Tempe
country: United States
facility: Ardelyx Investigative Site 277
state: Arizona
city: Tucson
country: United States
facility: Ardelyx Investigative Site 269
state: Arizona
city: Tucson
country: United States
facility: Ardelyx Investigative Site 187
state: Arizona
city: Tucson
country: United States
facility: Ardelyx Investigative Site 199
state: Arizona
city: Harrisburg
country: United States
facility: Ardelyx Investigative Site 140
state: Arkansas
city: Little Rock
country: United States
facility: Ardelyx Investigative Site 274
state: Arkansas
city: Little Rock
country: United States
facility: Ardelyx Investigative Site 161
state: Arkansas
city: Little Rock
country: United States
facility: Ardelyx Investigative Site 122
state: Arkansas
city: North Little Rock
country: United States
facility: Ardelyx Investigative Site 129
state: Arkansas
city: Canoga Park
country: United States
facility: Ardelyx Investigative Site 105
state: California
city: Chula Vista
country: United States
facility: Ardelyx Investigative Site 143
state: California
city: Encino
country: United States
facility: Ardelyx Investigative Site 146
state: California
city: Encino
country: United States
facility: Ardelyx Investigative Site 147
state: California
city: Lomita
country: United States
facility: Ardelyx Investigative Site 107
state: California
city: North Hollywood
country: United States
facility: Ardelyx Investigative Site 112
state: California
city: Northridge
country: United States
facility: Ardelyx Investigative Site 110
state: California
city: San Diego
country: United States
facility: Ardelyx Investigative Site 294
state: California
city: Thousand Oaks
country: United States
facility: Ardelyx Investigative Site 108
state: California
city: Cutler Bay
country: United States
facility: Ardelyx Investigative Site 178
state: Florida
city: Fort Lauderdale
country: United States
facility: Ardelyx Investigative Site 131
state: Florida
city: Hialeah
country: United States
facility: Ardelyx Investigative Site 136
state: Florida
city: Hialeah
country: United States
facility: Ardelyx Investigative Site 130
state: Florida
city: Homestead
country: United States
facility: Ardelyx Investigative Site 287
state: Florida
city: Miami Lakes
country: United States
facility: Ardelyx Investigative Site 127
state: Florida
city: Miami Springs
country: United States
facility: Ardelyx Investigative Site 123
state: Florida
city: Miami
country: United States
facility: Ardelyx Investigative Site 106
state: Florida
city: Pompano Beach
country: United States
facility: Ardelyx Investigative Site 126
state: Florida
city: Port Orange
country: United States
facility: Ardelyx Investigative Site 132
state: Florida
city: Saint Petersburg
country: United States
facility: Ardelyx Investigative Site 150
state: Florida
city: West Palm Beach
country: United States
facility: Ardelyx Investigative Site 254
state: Florida
city: Athens
country: United States
facility: Ardelyx Investigative Site 234
state: Georgia
city: Atlanta
country: United States
facility: Ardelyx Investigative Site 138
state: Georgia
city: Atlanta
country: United States
facility: Ardelyx Investigative Site 148
state: Georgia
city: Norcross
country: United States
facility: Ardelyx Investigative Site 137
state: Georgia
city: Savannah
country: United States
facility: Ardelyx Investigative Site 213
state: Georgia
city: Snellville
country: United States
facility: Ardelyx Investigative Site 124
state: Georgia
city: Boise
country: United States
facility: Ardelyx Investigative Site 157
state: Idaho
city: Blue Island
country: United States
facility: Ardelyx Investigative Site 102
state: Illinois
city: Evanston
country: United States
facility: Ardelyx Investigative Site 162
state: Illinois
city: Oak Lawn
country: United States
facility: Ardelyx Investigative Site 202
state: Illinois
city: Topeka
country: United States
facility: Ardelyx Investigative Site 259
state: Kansas
city: Crowley
country: United States
facility: Ardelyx Investigative Site 192
state: Louisiana
city: Metairie
country: United States
facility: Ardelyx Investigative Site 188
state: Louisiana
city: Monroe
country: United States
facility: Ardelyx Investigative Site 177
state: Louisiana
city: Zachary
country: United States
facility: Ardelyx Investigative Site 198
state: Louisiana
city: Hagerstown
country: United States
facility: Ardelyx Investigative Site 278
state: Maryland
city: Towson
country: United States
facility: Ardelyx Investigative Site 255
state: Maryland
city: Boston
country: United States
facility: Ardelyx Investigative Site 135
state: Massachusetts
city: Brockton
country: United States
facility: Ardelyx Investigative Site 267
state: Massachusetts
city: Caro
country: United States
facility: Ardelyx Investigative Site 119
state: Michigan
city: Chesterfield
country: United States
facility: Ardelyx Investigative Site 128
state: Michigan
city: Saginaw
country: United States
facility: Ardelyx Investigative Site 224
state: Michigan
city: Belton
country: United States
facility: Ardelyx Investigative Site 125
state: Missouri
city: Billings
country: United States
facility: Ardelyx Investigative Site 156
state: Montana
city: Omaha
country: United States
facility: Ardelyx Investigative Site 142
state: Nebraska
city: Las Vegas
country: United States
facility: Ardelyx Investigative Site 275
state: Nevada
city: Las Vegas
country: United States
facility: Ardelyx Investigative Site 276
state: Nevada
city: Las Vegas
country: United States
facility: Ardelyx Investigative Site 182
state: Nevada
city: Vineland
country: United States
facility: Ardelyx Investigative Site 175
state: New Jersey
city: Albuquerque
country: United States
facility: Ardelyx Investigative Site 293
state: New Mexico
city: Brooklyn
country: United States
facility: Ardelyx Investigative Site 151
state: New York
city: Great Neck
country: United States
facility: Ardelyx Investigative Site 170
state: New York
city: Hartsdale
country: United States
facility: Ardelyx Investigative Site 225
state: New York
city: New Windsor
country: United States
facility: Ardelyx Investigative Site 206
state: New York
city: New York
country: United States
facility: Ardelyx Investigative Site 183
state: New York
city: Asheville
country: United States
facility: Ardelyx Investigative Site 226
state: North Carolina
city: Charlotte
country: United States
facility: Ardelyx Investigative Site 166
state: North Carolina
city: Fayetteville
country: United States
facility: Ardelyx Investigative Site 205
state: North Carolina
city: Greensboro
country: United States
facility: Ardelyx Investigative Site 104
state: North Carolina
city: Kinston
country: United States
facility: Ardelyx Investigative Site 174
state: North Carolina
city: Winston-Salem
country: United States
facility: Ardelyx Investigative Site 280
state: North Carolina
city: Beavercreek
country: United States
facility: Ardelyx Investigative Site 172
state: Ohio
city: Cincinnati
country: United States
facility: Ardelyx Investigative Site 223
state: Ohio
city: Cincinnati
country: United States
facility: Ardelyx Investigative Site 201
state: Ohio
city: Columbus
country: United States
facility: Ardelyx Investigative Site 139
state: Ohio
city: Dayton
country: United States
facility: Ardelyx Investigative Site 173
state: Ohio
city: Huber Heights
country: United States
facility: Ardelyx Investigative Site 171
state: Ohio
city: Mentor
country: United States
facility: Ardelyx Investigative Site 117
state: Ohio
city: Springfield
country: United States
facility: Ardelyx Investigative Site 247
state: Ohio
city: Jenkintown
country: United States
facility: Ardelyx Investigative Site 144
state: Pennsylvania
city: Mount Pleasant
country: United States
facility: Ardelyx Investigative Site 289
state: South Carolina
city: Myrtle Beach
country: United States
facility: Ardelyx Investigative Site 184
state: South Carolina
city: North Charleston
country: United States
facility: Ardelyx Investigative Site 281
state: South Carolina
city: Sioux Falls
country: United States
facility: Ardelyx Investigative Site 261
state: South Dakota
city: Chattanooga
country: United States
facility: Ardelyx Investigative Site 134
state: Tennessee
city: Franklin
country: United States
facility: Ardelyx Investigative Site 121
state: Tennessee
city: Hermitage
country: United States
facility: Ardelyx Investigative Site 189
state: Tennessee
city: Jackson
country: United States
facility: Ardelyx Investigative Site 133
state: Tennessee
city: Knoxville
country: United States
facility: Ardelyx Investigative Site 109
state: Tennessee
city: Nashville
country: United States
facility: Ardelyx Investigative Site 235
state: Tennessee
city: Corpus Christi
country: United States
facility: Ardelyx Investigative Site 164
state: Texas
city: Corsicana
country: United States
facility: Ardelyx Investigative Site 197
state: Texas
city: Houston
country: United States
facility: Ardelyx Investigative Site 185
state: Texas
city: Houston
country: United States
facility: Ardelyx Investigative Site 120
state: Texas
city: McKinney
country: United States
facility: Ardelyx Investigative Site 113
state: Texas
city: Plano
country: United States
facility: Ardelyx Investigative Site 111
state: Texas
city: Plano
country: United States
facility: Ardelyx Investigative Site 118
state: Texas
city: San Antonio
country: United States
facility: Ardelyx Investigative Site 101
state: Texas
city: San Antonio
country: United States
facility: Ardelyx Investigative Site 240
state: Texas
city: Orem
country: United States
facility: Ardelyx Investigative Site 159
state: Utah
city: Sandy
country: United States
facility: Ardelyx Investigative Site 207
state: Utah
city: South Ogden
country: United States
facility: Ardelyx Investigative Site 155
state: Utah
city: Norfolk
country: United States
facility: Ardelyx Investigative Site 231
state: Virginia
city: Richmond
country: United States
facility: Ardelyx Investigative Site 141
state: Virginia
Study officials:
affiliation: Ardelyx, Inc.
name: David P Rosenbaum, Ph.D.
role: STUDY_CHAIR
References:
citation: Chey WD, Lembo AJ, Yang Y, Rosenbaum DP. Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 26-Week, Placebo-Controlled Phase 3 Trial (T3MPO-2). Am J Gastroenterol. 2021 Jun 1;116(6):1294-1303. doi: 10.14309/ajg.0000000000001056.
citation: Chey WD, Lembo AJ, Rosenbaum DP. Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 12-Week, Placebo-Controlled Phase 3 Trial (T3MPO-1). Am J Gastroenterol. 2020 Feb;115(2):281-293. doi: 10.14309/ajg.0000000000000516.