Constipation Predominant Irritable Bowel Syndrome
Conditions
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.
Interventions
DRUGTenapanor
DRUGPlacebo
Sponsors
Ardelyx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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? |
| 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 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 50mg BID Tenapanor
Tenapanor | 307 |
| Placebo Placebo
Placebo | 299 |
| Total | 606 |
Baseline characteristics
| Characteristic | 50mg BID | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 45 years STANDARD_DEVIATION 13.38 | 44.9 years STANDARD_DEVIATION 13.04 | 45 years STANDARD_DEVIATION 13.2 |
| Body Mass Index (BMI) | 29.88 kg/m^2 STANDARD_DEVIATION 7.198 | 29.30 kg/m^2 STANDARD_DEVIATION 6.442 | 29.60 kg/m^2 STANDARD_DEVIATION 6.836 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 98 Participants | 83 Participants | 181 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 209 Participants | 216 Participants | 425 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 4 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 88 Participants | 100 Participants | 188 Participants |
| Race (NIH/OMB) More than one race | 8 Participants | 7 Participants | 15 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 201 Participants | 186 Participants | 387 Participants |
| Sex: Female, Male Female | 244 Participants | 249 Participants | 493 Participants |
| Sex: Female, Male Male | 63 Participants | 50 Participants | 113 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 307 | 0 / 299 |
| other Total, other adverse events | 45 / 307 | 5 / 299 |
| serious Total, serious adverse events | 6 / 307 | 0 / 299 |
Outcome results
Primary
6 of 12 Week Overall Responder Rate
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.
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50mg BID | 6 of 12 Week Overall Responder Rate | 83 Participants |
| Placebo | 6 of 12 Week Overall Responder Rate | 56 Participants |
p-value: <0.02Cochran-Mantel-Haenszel
Secondary
6 of 12 Week Overall Abdominal Pain Responder Rate
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.
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50mg BID | 6 of 12 Week Overall Abdominal Pain Responder Rate | 135 Participants |
| Placebo | 6 of 12 Week Overall Abdominal Pain Responder Rate | 99 Participants |
p-value: <0.008Cochran-Mantel-Haenszel
Secondary
6 of 12 Week Overall Complete Spontaneous Bowel Movement (CSBM)Responder Rate
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?
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50mg BID | 6 of 12 Week Overall Complete Spontaneous Bowel Movement (CSBM)Responder Rate | 104 Participants |
| Placebo | 6 of 12 Week Overall Complete Spontaneous Bowel Movement (CSBM)Responder Rate | 88 Participants |
Secondary
9 of 12 Week Overall Abdominal Pain Responder Rate
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.
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50mg BID | 9 of 12 Week Overall Abdominal Pain Responder Rate | 93 Participants |
| Placebo | 9 of 12 Week Overall Abdominal Pain Responder Rate | 58 Participants |
p-value: <0.003Cochran-Mantel-Haenszel
Secondary
9 of 12 Week Overall CSBM Responder Rate
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?
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50mg BID | 9 of 12 Week Overall CSBM Responder Rate | 52 Participants |
| Placebo | 9 of 12 Week Overall CSBM Responder Rate | 15 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
9 of 12 Week Overall Responder Rate
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.
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50mg BID | 9 of 12 Week Overall Responder Rate | 42 Participants |
| Placebo | 9 of 12 Week Overall Responder Rate | 10 Participants |
p-value: <0.001Cochran-Mantel-Haenszel