Irritable Bowel Syndrome With Constipation
Conditions
Brief summary
The objectives of this study are to evaluate the safety, efficacy, and dose response of two delayed release formulations of linaclotide (DR; DR formulation 1 is DR1; DR formulation 2 is DR2) administered orally to patients with irritable bowel syndrome with constipation (IBS-C). Additional objectives include understanding how the two DR formulations compare with each other and with the FDA-approved 290 μg LINZESS® (the immediate release \[IR\] formulation of linaclotide).
Interventions
DRUGLinaclotide
Oral, once daily
DRUGMatching Placebo
Oral, once daily
Sponsors
Forest Laboratories
Ironwood Pharmaceuticals, Inc.
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Patient has completed a colonoscopy according to the American Gastroenterological Association (AGA) criteria, with no clinically significant findings * Patient has no clinically significant findings on a physical examination and clinical laboratory tests * Patient meets protocol criteria for diagnosis of IBS-C * Patient demonstrates continued IBS-C through Pretreatment Period * Patient maintains a minimum level of compliance with daily diary
Exclusion criteria
* Patient has history of loose or watery stools * Patient has symptoms of or been diagnosed with a medical condition that may contribute to abdominal pain * Patient has a structural abnormality of the gastrointestinal (GI) tract or a disease or condition that can affect GI motility * Patient has any protocol-excluded or clinically significant medical or surgical history that could confound the study assessments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | Baseline, up to Week 12 | Abdominal pain assessment was based on an 11-point numerical rating scale (0=No symptom; 10=Worst possible) assessing the symptom at its worst in past 24 hours. A participant's weekly abdominal pain score is the average of the nonmissing abdominal pain scores reported by the participant during each week. |
| Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | Baseline, up to Week 12 | Abdominal pain assessment was based on an 11-point numerical rating scale (0=No symptom; 10=Worst possible) assessing the symptom at its worst in past 24 hours. A participant's weekly abdominal pain score is the average of the nonmissing abdominal pain scores reported by the participant during each week. |
| Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | Baseline, up to Week 12 | A participant's weekly CSBM frequency rate is the CSBM rate (CSBMs/week) calculated over that week. |
| Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | Baseline, up to Week 12 | A participant's weekly CSBM frequency rate is the CSBM rate (CSBMs/week) calculated over that week. |
| Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | up to Week 12 | A 6/12 Week APC +1 Responder is a participant who meets the Weekly APC +1 Responder criteria for at least 6 out of the 12 weeks of the Treatment Period. * Weekly APC +1 Responder: A participant who meets the criteria to be a Weekly Abdominal Pain Responder and a Weekly CSBM +1 Responder. * Weekly Abdominal Pain Responder: A participant who has a decrease from baseline of ≥30% in the mean daily worst abdominal pain scores for that week. * Weekly CSBM +1 Responder: A participant who has an increase from baseline of ≥1 in the CSBM weekly rate for that week. A participant with \<4 days of completed eDiary data for that week is not considered a responder for that week. |
| Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | up to Week 12 | A 6/12 Week APC +1 Responder is a participant who meets the Weekly APC +1 Responder criteria for at least 6 out of the 12 weeks of the Treatment Period. * Weekly APC +1 Responder: A participant who meets the criteria to be a Weekly Abdominal Pain Responder and a Weekly CSBM +1 Responder. * Weekly Abdominal Pain Responder: A participant who has a decrease from baseline of ≥30% in the mean daily worst abdominal pain scores for that week. * Weekly CSBM +1 Responder: A participant who has an increase from baseline of ≥1 in the CSBM weekly rate for that week. A participant with \<4 days of completed eDiary data for that week is not considered a responder for that week. |
Countries
United States
Participant flow
Pre-assignment details
A total of 227 of the 759 participants who signed an informed consent form and entered the Pretreatment Period were not randomized into the study, and were identified as pretreatment failures.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo: once daily (QD) for 12 weeks | 66 |
| Linaclotide IR 290 μg Linaclotide IR formulation: 290 μg QD for 12 weeks | 66 |
| Linaclotide DR1 30 μg Linaclotide DR1 30 μg QD for 12 weeks | 67 |
| Linaclotide DR1 100 μg Linaclotide DR1 100 μg QD for 12 weeks | 67 |
| Linaclotide DR1 300 μg Linaclotide DR1 300 μg QD for 12 weeks | 67 |
| Linaclotide DR2 30 μg Linaclotide DR2 30 μg QD for 12 weeks | 67 |
| Linaclotide DR2 100 μg Linaclotide DR2 100 μg QD for 12 weeks | 66 |
| Linaclotide DR2 300 μg Linaclotide DR2 300 μg QD for 12 weeks | 66 |
| Total | 532 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 4 | 1 | 5 | 3 | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 | 3 | 2 | 2 | 3 | 3 | 3 |
| Overall Study | Lost to Follow-up | 3 | 5 | 3 | 3 | 2 | 5 | 1 | 4 |
| Overall Study | Other Not Specified | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 1 | 0 | 0 | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 3 | 1 | 3 | 5 | 4 | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo | Linaclotide IR 290 μg | Linaclotide DR1 30 μg | Linaclotide DR1 100 μg | Linaclotide DR1 300 μg | Linaclotide DR2 30 μg | Linaclotide DR2 100 μg | Linaclotide DR2 300 μg | Total |
|---|---|---|---|---|---|---|---|---|---|
| Abdominal Pain | 6.41 units on a scale STANDARD_DEVIATION 1.85 | 6.18 units on a scale STANDARD_DEVIATION 1.77 | 6.20 units on a scale STANDARD_DEVIATION 1.59 | 6.18 units on a scale STANDARD_DEVIATION 1.67 | 6.38 units on a scale STANDARD_DEVIATION 1.82 | 6.07 units on a scale STANDARD_DEVIATION 1.68 | 6.48 units on a scale STANDARD_DEVIATION 1.53 | 6.09 units on a scale STANDARD_DEVIATION 1.68 | 6.25 units on a scale STANDARD_DEVIATION 1.69 |
| Age, Continuous | 45.4 years STANDARD_DEVIATION 14.7 | 44.1 years STANDARD_DEVIATION 14.4 | 44.8 years STANDARD_DEVIATION 14.9 | 44.7 years STANDARD_DEVIATION 13.7 | 46.5 years STANDARD_DEVIATION 12.7 | 42.3 years STANDARD_DEVIATION 12.6 | 47.9 years STANDARD_DEVIATION 12.8 | 45.2 years STANDARD_DEVIATION 14.4 | 45.1 years STANDARD_DEVIATION 13.8 |
| Complete Spontaneous Bowel Movement (CBSM) Weekly Rate | 0.29 CBSM/week STANDARD_DEVIATION 0.56 | 0.34 CBSM/week STANDARD_DEVIATION 0.61 | 0.35 CBSM/week STANDARD_DEVIATION 0.56 | 0.22 CBSM/week STANDARD_DEVIATION 0.46 | 0.27 CBSM/week STANDARD_DEVIATION 0.54 | 0.35 CBSM/week STANDARD_DEVIATION 0.62 | 0.31 CBSM/week STANDARD_DEVIATION 0.61 | 0.33 CBSM/week STANDARD_DEVIATION 0.56 | 0.31 CBSM/week STANDARD_DEVIATION 0.57 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 14 Participants | 16 Participants | 17 Participants | 16 Participants | 18 Participants | 15 Participants | 21 Participants | 127 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants | 52 Participants | 51 Participants | 50 Participants | 51 Participants | 49 Participants | 51 Participants | 45 Participants | 405 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 10 Participants | 3 Participants | 2 Participants | 7 Participants | 6 Participants | 2 Participants | 3 Participants | 35 Participants |
| Race/Ethnicity, Customized Black/African American | 25 Participants | 11 Participants | 18 Participants | 17 Participants | 19 Participants | 19 Participants | 22 Participants | 14 Participants | 145 Participants |
| Race/Ethnicity, Customized Caucasian | 38 Participants | 43 Participants | 45 Participants | 47 Participants | 41 Participants | 42 Participants | 40 Participants | 48 Participants | 344 Participants |
| Race/Ethnicity, Customized Non-Caucasian | 28 Participants | 23 Participants | 22 Participants | 20 Participants | 26 Participants | 25 Participants | 26 Participants | 18 Participants | 188 Participants |
| Race/Ethnicity, Customized Other, Not Specified | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 8 Participants |
| Sex: Female, Male Female | 53 Participants | 53 Participants | 59 Participants | 59 Participants | 55 Participants | 50 Participants | 52 Participants | 62 Participants | 443 Participants |
| Sex: Female, Male Male | 13 Participants | 13 Participants | 8 Participants | 8 Participants | 12 Participants | 17 Participants | 14 Participants | 4 Participants | 89 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 66 | 0 / 66 | 0 / 67 | 0 / 67 | 0 / 67 | 0 / 67 | 0 / 66 | 0 / 66 |
| other Total, other adverse events | 1 / 66 | 10 / 66 | 4 / 67 | 9 / 67 | 8 / 67 | 0 / 67 | 1 / 66 | 2 / 66 |
| serious Total, serious adverse events | 1 / 66 | 1 / 66 | 0 / 67 | 0 / 67 | 0 / 67 | 0 / 67 | 0 / 66 | 0 / 66 |
Outcome results
Primary
Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR1 or IR vs. Placebo
Abdominal pain assessment was based on an 11-point numerical rating scale (0=No symptom; 10=Worst possible) assessing the symptom at its worst in past 24 hours. A participant's weekly abdominal pain score is the average of the nonmissing abdominal pain scores reported by the participant during each week.
Time frame: Baseline, up to Week 12
Population: Intent to Treat Population: all randomized participants who received at least one dose of study drug (evaluated according to assigned treatment).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | -1.370 score on a scale | Standard Error 0.241 |
| Linaclotide IR 290 μg | Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | -1.938 score on a scale | Standard Error 0.241 |
| Linaclotide DR1 30 μg | Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | -1.667 score on a scale | Standard Error 0.234 |
| Linaclotide DR1 100 μg | Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | -1.656 score on a scale | Standard Error 0.24 |
| Linaclotide DR1 300 μg | Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | -2.140 score on a scale | Standard Error 0.236 |
p-value: 0.083995% CI: [-1.214, 0.076]mixed model repeated measures (MMRM)
p-value: 0.366195% CI: [-0.942, 0.348]MMRM
p-value: 0.386995% CI: [-0.936, 0.363]MMRM
p-value: 0.019995% CI: [-1.419, -0.123]MMRM
p-value: 0.0276Trend Test
Primary
Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR2 or IR vs. Placebo
Abdominal pain assessment was based on an 11-point numerical rating scale (0=No symptom; 10=Worst possible) assessing the symptom at its worst in past 24 hours. A participant's weekly abdominal pain score is the average of the nonmissing abdominal pain scores reported by the participant during each week.
Time frame: Baseline, up to Week 12
Population: Intent to Treat Population: all randomized participants who received at least one dose of study drug (evaluated according to assigned treatment).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | -1.370 score on a scale | Standard Error 0.241 |
| Linaclotide IR 290 μg | Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | -1.938 score on a scale | Standard Error 0.241 |
| Linaclotide DR1 30 μg | Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | -1.825 score on a scale | Standard Error 0.238 |
| Linaclotide DR1 100 μg | Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | -1.669 score on a scale | Standard Error 0.235 |
| Linaclotide DR1 300 μg | Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | -1.628 score on a scale | Standard Error 0.239 |
p-value: 0.083995% CI: [-1.214, 0.076]MMRM
p-value: 0.166995% CI: [-1.102, 0.191]MMRM
p-value: 0.363795% CI: [-0.947, 0.348]MMRM
p-value: 0.433395% CI: [-0.905, 0.389]MMRM
p-value: 0.5528Trend Test
Primary
Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR1 or IR vs. Placebo
A participant's weekly CSBM frequency rate is the CSBM rate (CSBMs/week) calculated over that week.
Time frame: Baseline, up to Week 12
Population: Intent to Treat Population: all randomized participants who received at least one dose of study drug (evaluated according to assigned treatment).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | 1.115 CSBMs/week | Standard Error 0.285 |
| Linaclotide IR 290 μg | Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | 2.107 CSBMs/week | Standard Error 0.286 |
| Linaclotide DR1 30 μg | Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | 1.163 CSBMs/week | Standard Error 0.278 |
| Linaclotide DR1 100 μg | Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | 1.414 CSBMs/week | Standard Error 0.283 |
| Linaclotide DR1 300 μg | Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | 1.776 CSBMs/week | Standard Error 0.279 |
p-value: 0.01195% CI: [0.228, 1.756]MMRM
p-value: 0.901395% CI: [-0.716, 0.812]MMRM
p-value: 0.444795% CI: [-0.469, 1.067]MMRM
p-value: 0.090495% CI: [-0.104, 1.428]MMRM
p-value: 0.07Trend Test
Primary
Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR2 or IR vs. Placebo
A participant's weekly CSBM frequency rate is the CSBM rate (CSBMs/week) calculated over that week.
Time frame: Baseline, up to Week 12
Population: Intent to Treat Population: all randomized participants who received at least one dose of study drug (evaluated according to assigned treatment).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | 1.115 CSBMs/week | Standard Error 0.285 |
| Linaclotide IR 290 μg | Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | 2.107 CSBMs/week | Standard Error 0.286 |
| Linaclotide DR1 30 μg | Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | 1.275 CSBMs/week | Standard Error 0.282 |
| Linaclotide DR1 100 μg | Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | 1.019 CSBMs/week | Standard Error 0.278 |
| Linaclotide DR1 300 μg | Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | 0.869 CSBMs/week | Standard Error 0.282 |
p-value: 0.01195% CI: [0.228, 1.756]MMRM
p-value: 0.680195% CI: [-0.604, 0.925]MMRM
p-value: 0.806995% CI: [-0.861, 0.67]MMRM
p-value: 0.527595% CI: [-1.011, 0.519]MMRM
p-value: 0.4201Trend Test
Primary
Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR1 or IR vs. Placebo
A 6/12 Week APC +1 Responder is a participant who meets the Weekly APC +1 Responder criteria for at least 6 out of the 12 weeks of the Treatment Period. * Weekly APC +1 Responder: A participant who meets the criteria to be a Weekly Abdominal Pain Responder and a Weekly CSBM +1 Responder. * Weekly Abdominal Pain Responder: A participant who has a decrease from baseline of ≥30% in the mean daily worst abdominal pain scores for that week. * Weekly CSBM +1 Responder: A participant who has an increase from baseline of ≥1 in the CSBM weekly rate for that week. A participant with \<4 days of completed eDiary data for that week is not considered a responder for that week.
Time frame: up to Week 12
Population: Intent to Treat Population: all randomized participants who received at least one dose of study drug (evaluated according to assigned treatment).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | Responder | 14 Participants |
| Placebo | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | Non-Responder | 52 Participants |
| Linaclotide IR 290 μg | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | Non-Responder | 45 Participants |
| Linaclotide IR 290 μg | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | Responder | 21 Participants |
| Linaclotide DR1 30 μg | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | Non-Responder | 49 Participants |
| Linaclotide DR1 30 μg | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | Responder | 18 Participants |
| Linaclotide DR1 100 μg | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | Responder | 17 Participants |
| Linaclotide DR1 100 μg | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | Non-Responder | 50 Participants |
| Linaclotide DR1 300 μg | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | Non-Responder | 41 Participants |
| Linaclotide DR1 300 μg | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR1 or IR vs. Placebo | Responder | 26 Participants |
p-value: 0.166395% CI: [0.79, 3.7]Cochran-Mantel-Haenszel
p-value: 0.439995% CI: [0.61, 3.17]Cochran-Mantel-Haenszel
p-value: 0.55495% CI: [0.57, 2.85]Cochran-Mantel-Haenszel
p-value: 0.026295% CI: [1.1, 5.19]Cochran-Mantel-Haenszel
p-value: 0.0249Correlation test
Primary
Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR2 or IR vs. Placebo
A 6/12 Week APC +1 Responder is a participant who meets the Weekly APC +1 Responder criteria for at least 6 out of the 12 weeks of the Treatment Period. * Weekly APC +1 Responder: A participant who meets the criteria to be a Weekly Abdominal Pain Responder and a Weekly CSBM +1 Responder. * Weekly Abdominal Pain Responder: A participant who has a decrease from baseline of ≥30% in the mean daily worst abdominal pain scores for that week. * Weekly CSBM +1 Responder: A participant who has an increase from baseline of ≥1 in the CSBM weekly rate for that week. A participant with \<4 days of completed eDiary data for that week is not considered a responder for that week.
Time frame: up to Week 12
Population: Intent to Treat Population: all randomized participants who received at least one dose of study drug (evaluated according to assigned treatment).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | Responder | 14 Participants |
| Placebo | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | Non-Responder | 52 Participants |
| Linaclotide IR 290 μg | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | Responder | 21 Participants |
| Linaclotide IR 290 μg | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | Non-Responder | 45 Participants |
| Linaclotide DR1 30 μg | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | Responder | 16 Participants |
| Linaclotide DR1 30 μg | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | Non-Responder | 51 Participants |
| Linaclotide DR1 100 μg | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | Non-Responder | 50 Participants |
| Linaclotide DR1 100 μg | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | Responder | 16 Participants |
| Linaclotide DR1 300 μg | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | Responder | 14 Participants |
| Linaclotide DR1 300 μg | Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR2 or IR vs. Placebo | Non-Responder | 52 Participants |
p-value: 0.166395% CI: [0.79, 3.7]Cochran-Mantel-Haenszel
p-value: 0.77195% CI: [0.49, 2.58]Cochran-Mantel-Haenszel
p-value: 0.802195% CI: [0.48, 2.58]Cochran-Mantel-Haenszel
p-value: 0.801195% CI: [0.37, 2.14]Cochran-Mantel-Haenszel
p-value: 0.8578Correlation test