Irritable Bowel Syndrome Characterized by Constipation
Conditions
Keywords
Irritable Bowel Syndrome, Constipation, Linaclotide
Brief summary
The objective of this trial is to determine the efficacy and safety of linaclotide administered to patients with irritable bowel syndrome with constipation (IBS-C). The primary efficacy parameter is the percentage of patients in each treatment group that meet the protocol definition for Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder.
Interventions
Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study
DRUGMatching placebo
Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study
Sponsors
Ironwood Pharmaceuticals, Inc.
Forest Laboratories
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 meets protocol criteria for IBS: reports abdominal discomfort or pain that has two or more of the following three features: 1. Relieved with defecation 2. Onset associated with a change in frequency of stool 3. Onset associated with a change in form (appearance) of stool * Patient reports \< 3 bowel movements (BMs) per week (in the absence of any laxative, suppository, or enema use during the preceding 24 hours) and reports straining, lumpy or hard stools, and/or sensation of incomplete evacuation during \> 25% of BMs * Patient has successfully completed protocol procedures (with no clinically significant findings): physical exam, 12-lead ECG, or clinical laboratory tests (some patients may require a colonoscopy per American Gastroenterological Association (AGA) guidelines) * Patient is compliant with Interactive Voice Response System (IVRS) for daily diary reporting of BM habits and IBS symptoms
Exclusion criteria
* Patient has history of loose or watery stools for \>25% of BMs * Patient has a structural abnormality of the gastrointestinal (GI) tract or a history of a disease or condition that can affect GI motility * Patient has any protocol-excluded or clinically significant medical or surgical history or concomitant medication use that could confound the study assessments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 9 Out of 12 Weeks | Change from Baseline to Week 12 | A patient is considered to be an APC responder if, for at least 9 out of the 12 weeks of the treatment period, the patient had at least 3 CSBMs, experienced an increase of at least 1 CSBM from baseline, and experienced a decrease of at least 30 percent in their Abdominal Pain (AP) score from baseline during a particular week. The AP score assesses the worst of a patient's AP in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no AP and 10 represents very severe AP. A CSBM is defined as a spontaneous bowel movement, associated with a sense of complete evacuation. |
| Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder, 9 Out of 12 Weeks | Change from Baseline to Week 12 | A patient is considered to be a CSBM 3+1 responder if, for at least 9 out of the 12 weeks of the treatment period, the patient had at least 3 CSBMs and experienced an increase of at least 1 CSBM from baseline during a particular week. A CSBM was defined as a Spontaneous Bowel Movement (SBM) that was associated with a sense of complete evacuation. An SBM was defined as a bowel movement (BM) that occurred in the absence of laxative, enema, or suppository use on either the calendar day of the BM or the calendar day before the BM. |
| Abdominal Pain Responder, 9 Out of 12 Weeks | Change from Baseline to Week 12 | A patient is considered to be an abdominal pain responder if, for at least 9 out of the 12 weeks of the treatment period, they experienced a decrease of at least 30 percent in the mean abdominal pain score from baseline during a particular week. The Abdominal Pain score assesses the worst of a patient's abdominal pain in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no abdominal pain and 10 represents very severe abdominal pain. |
| Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 6 Out of 12 Weeks. | Change from Baseline to Week 12 | A patient is considered an APC responder if, for at least 6 of the 12 weeks of the treatment, the patient experienced an increase of at least 1 Complete Spontaneous Bowel Movement (CSBM) from baseline and experienced a decrease of at least 30 percent in their Abdominal Pain (AP)score during a particular week. The AP score assesses the worst of a patient's AP in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no AP and 10 represents very severe AP. A CSBM was defined as a Spontaneous Bowel Movement (SBM) that was associated with a sense of complete evacuation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 12-Week Change in Abdominal Pain Score | Change from Baseline to Week 12 | Abdominal Pain at its worst (in the last 24 hours) is based on an 11-point scale where 0 represents no abdominal pain and 10 represents very severe abdominal pain. |
| 12-Week Change in Abdominal Discomfort | Change from Baseline to Week 12 | Abdominal Discomfort is measured on an 11-point scale where a value of 0 is none and a value of 10 is very severe. |
| 12-Week Change in Bloating | Change from Baseline to Week 12 | Bloating was assessed on an 11-point scale where a value of 0 is none and a value of 10 is very severe. |
| 12-Week Complete Spontaneous Bowel Movement (CSBM) Frequency Rate | Change from Baseline to Week 12 | The number of CSBMs per week. |
| Abdominal Pain Responder for 6 Out of 12 Weeks | Change from Baseline to Week 12 | A patient is considered to be an abdominal pain responder if, for at least 6 out of the 12 weeks of the treatment period, they experienced a decrease of 30 percent or more in the abdominal pain score from baseline. The Abdominal Pain score assesses the worst of a patient's abdominal pain in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no abdominal pain and 10 represents very severe abdominal pain. |
| 12-Week Percent of Abdominal Pain-free (APF) Days | Change from Baseline to Week 12 | Abdominal pain free (APF) days are those days where the patient reported a score of '0' for abdominal pain at its worst Abdominal Pain at its worst (in the last 24 hours) is based on an 11-point scale where 0 represents no abdominal pain and 10 represents very severe abdominal pain. |
| Complete Spontaneous Bowl Movement (CSBM) Responder for 6 Weeks Out of 12 Weeks of Treatment | Change from Baseline to Week 12 | A patient is considered to be a CSBM responder if, for at least 6 out of the 12 weeks of the treatment period, an increase of at least 1 CSBM per week from baseline was experienced. |
| 12-Week Spontaneous Bowl Movement (SBM) Frequency Rate | Change from Baseline to Week 12 | The number of Spontaneous Bowl Movements experienced per week. |
| 12-Week Stool Consistency | Change from Baseline to Week 12 | The consistency of each BM was assessed by patients using the 7-point Bristol Stool Form Scale (BSFS) from 1 to 7. 1. = separate hard lumps like nuts \[difficult to pass\] 2. = sausage shaped but lumpy 3. = like a sausage but with cracks on surface 4. = like a sausage or snake, smooth and soft 5. = soft blobs with clear-cut edges \[passed easily\] 6. = fluffy pieces with ragged edges, a mushy stool 7. = watery, no solid pieces \[entirely liquid\]). |
| 12-Week Severity of Straining | Change from Baseline to Week 12 | Straining is measured on a 5-point scale where a value of 1 is not at all and a value of 5 is an extreme amount. |
Countries
Canada, United States
Participant flow
Recruitment details
Patient recruitment occurred over an eight month period from July 2009 to March 2009 at 118 study sites (111 in the United States, 7 in Canada).
Pre-assignment details
Patients went through a 14 to 21 day Pretreatment Period during which the patients provided qualifying bowel habit and symptoms, and rescue medicine usage information through an interactive voice response system (IVRS). All randomized patients needed an abdominal pain score ≥ 3. One randomized patient in the Placebo arm did not receive study drug.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Dose-matched placebo, oral administration, once per day. | 396 |
| Linaclotide Linaclotide 290µg, oral administration, once per day. | 406 |
| Total | 802 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 32 |
| Overall Study | Lack of Efficacy | 4 | 5 |
| Overall Study | Lost to Follow-up | 10 | 17 |
| Overall Study | Other Reason | 4 | 5 |
| Overall Study | Protocol Violation | 9 | 10 |
| Overall Study | Withdrawal by Subject | 25 | 25 |
Baseline characteristics
| Characteristic | Placebo | Linaclotide | Total |
|---|---|---|---|
| Age Continuous | 43.7 years STANDARD_DEVIATION 12.9 | 43.3 years STANDARD_DEVIATION 12.7 | 43.5 years STANDARD_DEVIATION 12.8 |
| Age, Customized 18 years to 64 years | 370 participants | 387 participants | 757 participants |
| Age, Customized 65 years and older | 26 participants | 19 participants | 45 participants |
| Region of Enrollment Canada | 29 participants | 32 participants | 61 participants |
| Region of Enrollment United States | 367 participants | 374 participants | 741 participants |
| Sex: Female, Male Female | 358 Participants | 368 Participants | 726 Participants |
| Sex: Female, Male Male | 38 Participants | 38 Participants | 76 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 22 / 396 | 93 / 406 | 41 / 333 | 1 / 154 | 5 / 158 |
| serious Total, serious adverse events | 2 / 396 | 2 / 406 | 0 / 333 | 0 / 154 | 0 / 158 |
Outcome results
Primary
Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 6 Out of 12 Weeks.
A patient is considered an APC responder if, for at least 6 of the 12 weeks of the treatment, the patient experienced an increase of at least 1 Complete Spontaneous Bowel Movement (CSBM) from baseline and experienced a decrease of at least 30 percent in their Abdominal Pain (AP)score during a particular week. The AP score assesses the worst of a patient's AP in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no AP and 10 represents very severe AP. A CSBM was defined as a Spontaneous Bowel Movement (SBM) that was associated with a sense of complete evacuation.
Time frame: Change from Baseline to Week 12
Population: 803 patients were randomized to treatment, and 802 patients received double-blind study drug. 800 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 6 Out of 12 Weeks. | Responder | 83 Participants |
| Placebo | Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 6 Out of 12 Weeks. | Non-responder | 312 Participants |
| Linaclotide | Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 6 Out of 12 Weeks. | Responder | 136 Participants |
| Linaclotide | Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 6 Out of 12 Weeks. | Non-responder | 269 Participants |
Comparison: Null Hypothesis: There is no difference between the 290 μg dose and placebo groups in the proportion of 6/12 Week APC + 1 Responders.~The power, adjusted for multiplicity, was expected to be 86% based on NCT00460811 (MCP-103-202) study data.p-value: <0.000195% CI: [1.4, 2.66]Cochran-Mantel-Haenszel
Primary
Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 9 Out of 12 Weeks
A patient is considered to be an APC responder if, for at least 9 out of the 12 weeks of the treatment period, the patient had at least 3 CSBMs, experienced an increase of at least 1 CSBM from baseline, and experienced a decrease of at least 30 percent in their Abdominal Pain (AP) score from baseline during a particular week. The AP score assesses the worst of a patient's AP in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no AP and 10 represents very severe AP. A CSBM is defined as a spontaneous bowel movement, associated with a sense of complete evacuation.
Time frame: Change from Baseline to Week 12
Population: 803 patients were randomized to treatment, and 802 patients received double-blind study drug. 800 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the Intent to Treat (ITT) Population. An observed-cases approach to missing postbaseline data was applied.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 9 Out of 12 Weeks | Responder | 20 Participants |
| Placebo | Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 9 Out of 12 Weeks | Nonresponder | 375 Participants |
| Linaclotide | Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 9 Out of 12 Weeks | Responder | 49 Participants |
| Linaclotide | Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 9 Out of 12 Weeks | Nonresponder | 356 Participants |
Comparison: Null Hypothesis: There is no difference between the 290 μg dose and placebo groups in the proportion of 9/12 Week APC 3 + 1 Responders.~The power, adjusted for multiplicity, was expected to be 93% based on NCT00460811 (MCP-103-202) study data.p-value: 0.000495% CI: [1.51, 4.47]Cochran-Mantel-Haenszel
Primary
Abdominal Pain Responder, 9 Out of 12 Weeks
A patient is considered to be an abdominal pain responder if, for at least 9 out of the 12 weeks of the treatment period, they experienced a decrease of at least 30 percent in the mean abdominal pain score from baseline during a particular week. The Abdominal Pain score assesses the worst of a patient's abdominal pain in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no abdominal pain and 10 represents very severe abdominal pain.
Time frame: Change from Baseline to Week 12
Population: 803 patients were randomized to treatment, and 802 patients received double-blind study drug. 800 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Abdominal Pain Responder, 9 Out of 12 Weeks | Responder | 107 Participants |
| Placebo | Abdominal Pain Responder, 9 Out of 12 Weeks | Non-responder | 288 Participants |
| Linaclotide | Abdominal Pain Responder, 9 Out of 12 Weeks | Responder | 139 Participants |
| Linaclotide | Abdominal Pain Responder, 9 Out of 12 Weeks | Non-responder | 266 Participants |
Comparison: Null Hypothesis: There is no difference between the 290 μg dose and placebo groups in the proportion of 9/12 Week Abdominal Pain Responders.~The power, adjusted for multiplicity, was expected to be 93% based on NCT00460811 (MCP-103-202) study data.p-value: 0.026295% CI: [1.04, 1.91]Cochran-Mantel-Haenszel
Primary
Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder, 9 Out of 12 Weeks
A patient is considered to be a CSBM 3+1 responder if, for at least 9 out of the 12 weeks of the treatment period, the patient had at least 3 CSBMs and experienced an increase of at least 1 CSBM from baseline during a particular week. A CSBM was defined as a Spontaneous Bowel Movement (SBM) that was associated with a sense of complete evacuation. An SBM was defined as a bowel movement (BM) that occurred in the absence of laxative, enema, or suppository use on either the calendar day of the BM or the calendar day before the BM.
Time frame: Change from Baseline to Week 12
Population: 803 patients were randomized to treatment, and 802 patients received double-blind study drug. 800 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder, 9 Out of 12 Weeks | Responder | 25 Participant |
| Placebo | Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder, 9 Out of 12 Weeks | Non-responder | 370 Participant |
| Linaclotide | Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder, 9 Out of 12 Weeks | Responder | 79 Participant |
| Linaclotide | Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder, 9 Out of 12 Weeks | Non-responder | 326 Participant |
Comparison: Null Hypothesis: There is no difference between the 290 μg dose and placebo groups in the proportion of 9/12 Week CSBM 3 + 1 Responders.~The power, adjusted for multiplicity, was expected to be 93% based on NCT00460811 (MCP-103-202) study data.p-value: <0.000195% CI: [2.26, 5.88]Cochran-Mantel-Haenszel
Secondary
12-Week Change in Abdominal Discomfort
Abdominal Discomfort is measured on an 11-point scale where a value of 0 is none and a value of 10 is very severe.
Time frame: Change from Baseline to Week 12
Population: 803 patients were randomized to treatment, and 802 patients received double-blind study drug. 800 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 12-Week Change in Abdominal Discomfort | -1.211 units on a scale | Standard Error 0.097 |
| Linaclotide | 12-Week Change in Abdominal Discomfort | -1.953 units on a scale | Standard Error 0.096 |
Secondary
12-Week Change in Abdominal Pain Score
Abdominal Pain at its worst (in the last 24 hours) is based on an 11-point scale where 0 represents no abdominal pain and 10 represents very severe abdominal pain.
Time frame: Change from Baseline to Week 12
Population: 803 patients were randomized to treatment, and 802 patients received double-blind study drug. 800 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 12-Week Change in Abdominal Pain Score | -1.129 units on a scale | Standard Error 0.094 |
| Linaclotide | 12-Week Change in Abdominal Pain Score | -1.869 units on a scale | Standard Error 0.093 |
Secondary
12-Week Change in Bloating
Bloating was assessed on an 11-point scale where a value of 0 is none and a value of 10 is very severe.
Time frame: Change from Baseline to Week 12
Population: 803 patients were randomized to treatment, and 802 patients received double-blind study drug. 800 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 12-Week Change in Bloating | -1.100 units on a scale | Standard Error 0.1 |
| Linaclotide | 12-Week Change in Bloating | -1.944 units on a scale | Standard Error 0.099 |
Secondary
12-Week Complete Spontaneous Bowel Movement (CSBM) Frequency Rate
The number of CSBMs per week.
Time frame: Change from Baseline to Week 12
Population: 803 patients were randomized to treatment, and 802 patients received double-blind study drug. 800 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 12-Week Complete Spontaneous Bowel Movement (CSBM) Frequency Rate | 0.705 CSBMs per Week | Standard Error 0.128 |
| Linaclotide | 12-Week Complete Spontaneous Bowel Movement (CSBM) Frequency Rate | 2.272 CSBMs per Week | Standard Error 0.127 |
Secondary
12-Week Percent of Abdominal Pain-free (APF) Days
Abdominal pain free (APF) days are those days where the patient reported a score of '0' for abdominal pain at its worst Abdominal Pain at its worst (in the last 24 hours) is based on an 11-point scale where 0 represents no abdominal pain and 10 represents very severe abdominal pain.
Time frame: Change from Baseline to Week 12
Population: 803 patients were randomized to treatment, and 802 patients received double-blind study drug. 800 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 12-Week Percent of Abdominal Pain-free (APF) Days | 5.31 Percent | Standard Deviation 15.74 |
| Linaclotide | 12-Week Percent of Abdominal Pain-free (APF) Days | 9.81 Percent | Standard Deviation 21.75 |
Secondary
12-Week Severity of Straining
Straining is measured on a 5-point scale where a value of 1 is not at all and a value of 5 is an extreme amount.
Time frame: Change from Baseline to Week 12
Population: 802 randomized patients received study drug. The 800 patients in the ITT population had at least 1 postrandomization entry of the primary efficacy assessment; 107 patients with no pretreatment spontaneous bowel movements were excluded from the Severity of Straining analysis. An observed-cases approach to missing postbaseline data was applied.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 12-Week Severity of Straining | -0.651 units on a scale | Standard Error 0.042 |
| Linaclotide | 12-Week Severity of Straining | -1.306 units on a scale | Standard Error 0.042 |
Secondary
12-Week Spontaneous Bowl Movement (SBM) Frequency Rate
The number of Spontaneous Bowl Movements experienced per week.
Time frame: Change from Baseline to Week 12
Population: 803 patients were randomized to treatment, and 802 patients received double-blind study drug. 800 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 12-Week Spontaneous Bowl Movement (SBM) Frequency Rate | 1.130 SBMs per week | Standard Error 0.0177 |
| Linaclotide | 12-Week Spontaneous Bowl Movement (SBM) Frequency Rate | 3.898 SBMs per week | Standard Error 0.176 |
Secondary
12-Week Stool Consistency
The consistency of each BM was assessed by patients using the 7-point Bristol Stool Form Scale (BSFS) from 1 to 7. 1. = separate hard lumps like nuts \[difficult to pass\] 2. = sausage shaped but lumpy 3. = like a sausage but with cracks on surface 4. = like a sausage or snake, smooth and soft 5. = soft blobs with clear-cut edges \[passed easily\] 6. = fluffy pieces with ragged edges, a mushy stool 7. = watery, no solid pieces \[entirely liquid\]).
Time frame: Change from Baseline to Week 12
Population: 802 randomized patients received study drug. The 800 patients in the ITT population had at least 1 postrandomization entry of the primary efficacy assessment; 107 patients with no pretreatment spontaneous bowel movements were excluded from the 12-Week Stool Consistency analysis. An observed-cases approach to missing postbaseline data was applied.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 12-Week Stool Consistency | 0.662 units on a scale | Standard Error 0.061 |
| Linaclotide | 12-Week Stool Consistency | 2.071 units on a scale | Standard Error 0.06 |
Secondary
Abdominal Pain Responder for 6 Out of 12 Weeks
A patient is considered to be an abdominal pain responder if, for at least 6 out of the 12 weeks of the treatment period, they experienced a decrease of 30 percent or more in the abdominal pain score from baseline. The Abdominal Pain score assesses the worst of a patient's abdominal pain in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no abdominal pain and 10 represents very severe abdominal pain.
Time frame: Change from Baseline to Week 12
Population: 803 patients were randomized to treatment, and 802 patients received double-blind study drug. 800 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Abdominal Pain Responder for 6 Out of 12 Weeks | Responder | 148 Participants |
| Placebo | Abdominal Pain Responder for 6 Out of 12 Weeks | Non-Responder | 247 Participants |
| Linaclotide | Abdominal Pain Responder for 6 Out of 12 Weeks | Responder | 203 Participants |
| Linaclotide | Abdominal Pain Responder for 6 Out of 12 Weeks | Non-Responder | 202 Participants |
Secondary
Complete Spontaneous Bowl Movement (CSBM) Responder for 6 Weeks Out of 12 Weeks of Treatment
A patient is considered to be a CSBM responder if, for at least 6 out of the 12 weeks of the treatment period, an increase of at least 1 CSBM per week from baseline was experienced.
Time frame: Change from Baseline to Week 12
Population: 803 patients were randomized to treatment, and 802 patients received double-blind study drug. 800 patients had at least 1 postrandomization entry of the primary efficacy assessment and were included in the ITT Population. An observed-cases approach to missing postbaseline data was applied.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Complete Spontaneous Bowl Movement (CSBM) Responder for 6 Weeks Out of 12 Weeks of Treatment | Responder | 117 Participants |
| Placebo | Complete Spontaneous Bowl Movement (CSBM) Responder for 6 Weeks Out of 12 Weeks of Treatment | Non-responder | 278 Participants |
| Linaclotide | Complete Spontaneous Bowl Movement (CSBM) Responder for 6 Weeks Out of 12 Weeks of Treatment | Responder | 197 Participants |
| Linaclotide | Complete Spontaneous Bowl Movement (CSBM) Responder for 6 Weeks Out of 12 Weeks of Treatment | Non-responder | 208 Participants |