Irritable Bowel Syndrome Characterized by Constipation
Conditions
Brief summary
The objective of this trial is to determine the effect of linaclotide on abdominal girth in IBS-C participants with the baseline symptoms of abdominal bloating and an increased abdominal girth.
Interventions
DRUGLinaclotide
Oral, once daily
DRUGPlacebo
Oral, one daily
Sponsors
Manchester University NHS Foundation Trust
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 meets protocol criteria for diagnosis of IBS-C, abdominal pain, abdominal bloating and abdominal girth
Exclusion criteria
* Patient has history of loose or watery stools * Patient has both clinically significant findings and unexplained clinically significant alarm symptoms * Patient has symptoms of or been diagnosed with a medical condition that may contribute to abdominal pain * 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 Abdominal Girth at Week 4 | Baseline, Week 4 | Mean change in abdominal girth (physical measure of bloating/distension) as measured by area under the curve (AUC), determined by 24-hour abdominal inductance plesthymography (AIP; with hourly averages). The AUC was calculated using the Trapezoidal method from the first reliable hour of measurement to last measurement (bedtime). The AUC for each participant was then individually standardized by dividing the total AUC over the period by that patient's number of hours of measurement included in the AUC. (Therefore, the time element was removed from the standardized AUC, and the unit of measure for this outcome is centimeters \[cm\]). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Maximal Abdominal Girth at Week 4 | Baseline, Week 4 | The maximum change in girth from the first hour, over the period from the 2nd hour to bedtime. The percentage change in maximum distension from baseline to 4 weeks will also be calculated. |
| Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 1 | Baseline, Week 1 | Symptom severity was assessed daily on an 11-point numerical rating scale (NRS) from 0 to 10, where 0 represents no symptoms and 10 represents very severe symptoms. Participants rated their abdominal pain, discomfort, bloating, and distension at its worst over the last 24 hours. Weekly average scores were calculated individually for abdominal pain, discomfort, bloating, distension. The abdominal score was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating combined. The abdominal score plus distension was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating and distension combined. |
| Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 2 | Baseline, Week 2 | Symptom severity was assessed daily on an 11-point NRS from 0 to 10, where 0 represents no symptoms and 10 represents very severe symptoms. Participants rated their abdominal pain, discomfort, bloating, and distension at its worst over the last 24 hours. Weekly average scores were calculated individually for abdominal pain, discomfort, bloating, distension. The abdominal score was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating combined. The abdominal score plus distension was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating and distension combined. |
| Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 3 | Baseline, Week 3 | Symptom severity was assessed daily on an 11-point NRS from 0 to 10, where 0 represents no symptoms and 10 represents very severe symptoms. Participants rated their abdominal pain, discomfort, bloating, and distension at its worst over the last 24 hours. Weekly average scores were calculated individually for abdominal pain, discomfort, bloating, distension. The abdominal score was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating combined. The abdominal score plus distension was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating and distension combined. |
| Change From Baseline in Abdominal Girth at Week 2 | Baseline, Week 2 | Mean change in abdominal girth (physical measure of bloating/distention) as measured by AUC, determined by 24-hour AIP (with hourly averages). The AUC was calculated using the Trapezoidal method from the first reliable hour of measurement to last measurement (bedtime). The AUC for each participant was then individually standardized by dividing the total AUC over the period by that patient's number of hours of measurement included in the AUC. (Therefore, the time element was removed from the standardized AUC, and the unit of measure for this outcome is centimeters \[cm\]). |
| Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 2 | Baseline, Week 2 | A digestive sensations questionnaire was used to record abdominal pain, discomfort, bloating, and distension symptoms on an hourly basis (waking hours only) during the 24 hours the participants are fitted with the AIP belt, using an 11-point NRS, with 0=no symptomatic sensations and 10=most severe symptomatic sensations. Daily diary scores for each of the digestive symptoms was averaged to obtain 'weekly' scores. |
| Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 4 | Baseline, Week 4 | A digestive sensations questionnaire was used to record abdominal pain, discomfort, bloating, and distension on an hourly basis (waking hours only) during the 24 hours the participants are fitted with the AIP belt, using an 11-point NRS, with 0=no symptomatic sensations and 10=most severe symptomatic sensations. Daily diary scores for each of the digestive symptoms was averaged to obtain 'weekly' scores. |
| Change From Baseline in Bristol Stool Form Scale (BSFS) Over Time | Baseline, Week 1, Week 2, Week 3, Week 4 | Daily stool consistency analyses were performed using the 7-point Bristol Stool Form Scale (BSFS), whereby a score of 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; and 7 = watery, no solid pieces (entirely liquid). Daily average recorded BSFS scores for each participant were computed for each week. |
| Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 4 | Baseline, Week 4 | Symptom severity was assessed daily on an 11-point NRS from 0 to 10, where 0 represents no symptoms and 10 represents very severe symptoms. Participants rated their abdominal pain, discomfort, bloating, and distension at its worst over the last 24 hours. Weekly average scores were calculated individually for abdominal pain, discomfort, bloating, distension. The abdominal score was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating combined. The abdominal score plus distension was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating and distension combined. |
Countries
United Kingdom
Participant flow
Pre-assignment details
The study included a 14-day screening period and a 7 day pretreatment period. The treatment period began with randomization and lasted for 4 weeks. Participants who met entry criteria were randomized (1:1) to once daily oral capsules containing 290 µg linaclotide or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Matching Placebo Placebo once daily for 4 weeks | 9 |
| 290 μg Linaclotide 290 μg linaclotide once daily for 4 weeks | 11 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Other, Not Specified | 1 | 2 |
Baseline characteristics
| Characteristic | 290 μg Linaclotide | Total | Matching Placebo |
|---|---|---|---|
| Age, Continuous | 35.2 years STANDARD_DEVIATION 12.82 | 35.5 years STANDARD_DEVIATION 11.49 | 35.8 years STANDARD_DEVIATION 10.38 |
| Race/Ethnicity, Customized Caucasian | 11 Participants | 20 Participants | 9 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 11 Participants | 20 Participants | 9 Participants |
| Sex: Female, Male Female | 11 Participants | 20 Participants | 9 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 10 |
| other Total, other adverse events | 1 / 9 | 7 / 10 |
| serious Total, serious adverse events | 1 / 9 | 0 / 10 |
Outcome results
Primary
Change From Baseline in Abdominal Girth at Week 4
Mean change in abdominal girth (physical measure of bloating/distension) as measured by area under the curve (AUC), determined by 24-hour abdominal inductance plesthymography (AIP; with hourly averages). The AUC was calculated using the Trapezoidal method from the first reliable hour of measurement to last measurement (bedtime). The AUC for each participant was then individually standardized by dividing the total AUC over the period by that patient's number of hours of measurement included in the AUC. (Therefore, the time element was removed from the standardized AUC, and the unit of measure for this outcome is centimeters \[cm\]).
Time frame: Baseline, Week 4
Population: Participants with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | Change From Baseline in Abdominal Girth at Week 4 | Baseline | 82.6 cm | Standard Deviation 11.8 |
| Matching Placebo | Change From Baseline in Abdominal Girth at Week 4 | Change From Baseline | -3.36 cm | Standard Deviation 4.04 |
| 290 μg Linaclotide | Change From Baseline in Abdominal Girth at Week 4 | Baseline | 83.7 cm | Standard Deviation 9.02 |
| 290 μg Linaclotide | Change From Baseline in Abdominal Girth at Week 4 | Change From Baseline | -0.632 cm | Standard Deviation 11.6 |
p-value: 0.283Wilcoxon rank sum test
Secondary
Change From Baseline in Abdominal Girth at Week 2
Mean change in abdominal girth (physical measure of bloating/distention) as measured by AUC, determined by 24-hour AIP (with hourly averages). The AUC was calculated using the Trapezoidal method from the first reliable hour of measurement to last measurement (bedtime). The AUC for each participant was then individually standardized by dividing the total AUC over the period by that patient's number of hours of measurement included in the AUC. (Therefore, the time element was removed from the standardized AUC, and the unit of measure for this outcome is centimeters \[cm\]).
Time frame: Baseline, Week 2
Population: Participants with an assessment at given time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Matching Placebo | Change From Baseline in Abdominal Girth at Week 2 | 0.535 cm | Standard Deviation 9.15 |
| 290 μg Linaclotide | Change From Baseline in Abdominal Girth at Week 2 | -2.3 cm | Standard Deviation 13.7 |
Secondary
Change From Baseline in Bristol Stool Form Scale (BSFS) Over Time
Daily stool consistency analyses were performed using the 7-point Bristol Stool Form Scale (BSFS), whereby a score of 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; and 7 = watery, no solid pieces (entirely liquid). Daily average recorded BSFS scores for each participant were computed for each week.
Time frame: Baseline, Week 1, Week 2, Week 3, Week 4
Population: Participants with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | Change From Baseline in Bristol Stool Form Scale (BSFS) Over Time | Week 2 | 0.57 score on a scale | Standard Deviation 0.86 |
| Matching Placebo | Change From Baseline in Bristol Stool Form Scale (BSFS) Over Time | Week 3 | 0.39 score on a scale | Standard Deviation 1.15 |
| Matching Placebo | Change From Baseline in Bristol Stool Form Scale (BSFS) Over Time | Week 4 | 0.35 score on a scale | Standard Deviation 1.11 |
| Matching Placebo | Change From Baseline in Bristol Stool Form Scale (BSFS) Over Time | Week 1 | 0.33 score on a scale | Standard Deviation 0.88 |
| 290 μg Linaclotide | Change From Baseline in Bristol Stool Form Scale (BSFS) Over Time | Week 1 | 1.53 score on a scale | Standard Deviation 1.57 |
| 290 μg Linaclotide | Change From Baseline in Bristol Stool Form Scale (BSFS) Over Time | Week 2 | 1.51 score on a scale | Standard Deviation 1.27 |
| 290 μg Linaclotide | Change From Baseline in Bristol Stool Form Scale (BSFS) Over Time | Week 4 | 1.56 score on a scale | Standard Deviation 1.13 |
| 290 μg Linaclotide | Change From Baseline in Bristol Stool Form Scale (BSFS) Over Time | Week 3 | 2.11 score on a scale | Standard Deviation 1.43 |
Secondary
Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 2
A digestive sensations questionnaire was used to record abdominal pain, discomfort, bloating, and distension symptoms on an hourly basis (waking hours only) during the 24 hours the participants are fitted with the AIP belt, using an 11-point NRS, with 0=no symptomatic sensations and 10=most severe symptomatic sensations. Daily diary scores for each of the digestive symptoms was averaged to obtain 'weekly' scores.
Time frame: Baseline, Week 2
Population: Participants with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 2 | Pain | -1.13 units on a scale | Standard Deviation 1.38 |
| Matching Placebo | Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 2 | Bloating | -1.03 units on a scale | Standard Deviation 1.54 |
| Matching Placebo | Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 2 | Discomfort | -1.01 units on a scale | Standard Deviation 1.53 |
| Matching Placebo | Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 2 | Distension | -0.97 units on a scale | Standard Deviation 1.5 |
| 290 μg Linaclotide | Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 2 | Distension | -0.36 units on a scale | Standard Deviation 1.14 |
| 290 μg Linaclotide | Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 2 | Discomfort | -1.00 units on a scale | Standard Deviation 1.34 |
| 290 μg Linaclotide | Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 2 | Bloating | -0.58 units on a scale | Standard Deviation 1.33 |
| 290 μg Linaclotide | Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 2 | Pain | -0.61 units on a scale | Standard Deviation 1.1 |
Secondary
Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 4
A digestive sensations questionnaire was used to record abdominal pain, discomfort, bloating, and distension on an hourly basis (waking hours only) during the 24 hours the participants are fitted with the AIP belt, using an 11-point NRS, with 0=no symptomatic sensations and 10=most severe symptomatic sensations. Daily diary scores for each of the digestive symptoms was averaged to obtain 'weekly' scores.
Time frame: Baseline, Week 4
Population: Participants with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 4 | Pain | -0.97 units on a scale | Standard Deviation 1.55 |
| Matching Placebo | Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 4 | Discomfort | -0.89 units on a scale | Standard Deviation 1.51 |
| Matching Placebo | Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 4 | Bloating | -1.01 units on a scale | Standard Deviation 1.57 |
| Matching Placebo | Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 4 | Distension | -1.03 units on a scale | Standard Deviation 1.49 |
| 290 μg Linaclotide | Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 4 | Distension | -1.42 units on a scale | Standard Deviation 0.64 |
| 290 μg Linaclotide | Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 4 | Pain | -0.87 units on a scale | Standard Deviation 1.33 |
| 290 μg Linaclotide | Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 4 | Bloating | -1.66 units on a scale | Standard Deviation 1.03 |
| 290 μg Linaclotide | Change From Baseline in Digestive Sensations (Subjective Bloating, Abdominal Discomfort, Abdominal Distension and Abdominal Pain) at Week 4 | Discomfort | -1.81 units on a scale | Standard Deviation 1.11 |
Secondary
Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 1
Symptom severity was assessed daily on an 11-point numerical rating scale (NRS) from 0 to 10, where 0 represents no symptoms and 10 represents very severe symptoms. Participants rated their abdominal pain, discomfort, bloating, and distension at its worst over the last 24 hours. Weekly average scores were calculated individually for abdominal pain, discomfort, bloating, distension. The abdominal score was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating combined. The abdominal score plus distension was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating and distension combined.
Time frame: Baseline, Week 1
Population: Participants with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 1 | Pain | -1.25 units on a scale | Standard Deviation 1.76 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 1 | Abdominal Score + Distension | -1.77 units on a scale | Standard Deviation 1.43 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 1 | Discomfort | -1.93 units on a scale | Standard Deviation 1.54 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 1 | Bloating | -2.00 units on a scale | Standard Deviation 1.48 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 1 | Distension | -1.91 units on a scale | Standard Deviation 1.41 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 1 | Abdominal Score | -1.73 units on a scale | Standard Deviation 1.5 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 1 | Discomfort | -0.97 units on a scale | Standard Deviation 2.05 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 1 | Pain | -0.75 units on a scale | Standard Deviation 1.88 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 1 | Abdominal Score | -0.71 units on a scale | Standard Deviation 1.58 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 1 | Distension | -0.15 units on a scale | Standard Deviation 1.02 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 1 | Abdominal Score + Distension | -0.57 units on a scale | Standard Deviation 1.36 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 1 | Bloating | -0.40 units on a scale | Standard Deviation 1.23 |
Secondary
Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 2
Symptom severity was assessed daily on an 11-point NRS from 0 to 10, where 0 represents no symptoms and 10 represents very severe symptoms. Participants rated their abdominal pain, discomfort, bloating, and distension at its worst over the last 24 hours. Weekly average scores were calculated individually for abdominal pain, discomfort, bloating, distension. The abdominal score was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating combined. The abdominal score plus distension was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating and distension combined.
Time frame: Baseline, Week 2
Population: Participants with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 2 | Abdominal Score + Distension | -2.41 units on a scale | Standard Deviation 1.18 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 2 | Discomfort | -2.51 units on a scale | Standard Deviation 1.15 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 2 | Distension | -2.51 units on a scale | Standard Deviation 1.37 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 2 | Abdominal Score | -2.38 units on a scale | Standard Deviation 1.19 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 2 | Bloating | -2.65 units on a scale | Standard Deviation 1.3 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 2 | Pain | -1.97 units on a scale | Standard Deviation 1.6 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 2 | Abdominal Score | -1.40 units on a scale | Standard Deviation 1.69 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 2 | Pain | -1.42 units on a scale | Standard Deviation 1.88 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 2 | Abdominal Score + Distension | -1.25 units on a scale | Standard Deviation 1.52 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 2 | Bloating | -1.04 units on a scale | Standard Deviation 1.54 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 2 | Discomfort | -1.73 units on a scale | Standard Deviation 2.27 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 2 | Distension | -0.78 units on a scale | Standard Deviation 1.33 |
Secondary
Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 3
Symptom severity was assessed daily on an 11-point NRS from 0 to 10, where 0 represents no symptoms and 10 represents very severe symptoms. Participants rated their abdominal pain, discomfort, bloating, and distension at its worst over the last 24 hours. Weekly average scores were calculated individually for abdominal pain, discomfort, bloating, distension. The abdominal score was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating combined. The abdominal score plus distension was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating and distension combined.
Time frame: Baseline, Week 3
Population: Participants with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 3 | Pain | -1.60 units on a scale | Standard Deviation 2.66 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 3 | Discomfort | -2.01 units on a scale | Standard Deviation 1.86 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 3 | Bloating | -2.02 units on a scale | Standard Deviation 1.67 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 3 | Distension | -1.79 units on a scale | Standard Deviation 1.8 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 3 | Abdominal Score | -1.88 units on a scale | Standard Deviation 1.95 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 3 | Abdominal Score + Distension | -1.86 units on a scale | Standard Deviation 1.87 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 3 | Abdominal Score | -1.82 units on a scale | Standard Deviation 1.64 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 3 | Pain | -2.07 units on a scale | Standard Deviation 1.88 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 3 | Distension | -1.05 units on a scale | Standard Deviation 1.37 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 3 | Discomfort | -2.25 units on a scale | Standard Deviation 2.26 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 3 | Abdominal Score + Distension | -1.64 units on a scale | Standard Deviation 1.46 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 3 | Bloating | -1.16 units on a scale | Standard Deviation 1.51 |
Secondary
Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 4
Symptom severity was assessed daily on an 11-point NRS from 0 to 10, where 0 represents no symptoms and 10 represents very severe symptoms. Participants rated their abdominal pain, discomfort, bloating, and distension at its worst over the last 24 hours. Weekly average scores were calculated individually for abdominal pain, discomfort, bloating, distension. The abdominal score was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating combined. The abdominal score plus distension was calculated as the weekly average from the daily scores of the individual items of pain, discomfort, bloating and distension combined.
Time frame: Baseline, Week 4
Population: Participants with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 4 | Abdominal Score | -1.83 units on a scale | Standard Deviation 1.84 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 4 | Discomfort | -1.94 units on a scale | Standard Deviation 1.63 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 4 | Abdominal Score + Distension | -1.80 units on a scale | Standard Deviation 1.75 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 4 | Bloating | -1.84 units on a scale | Standard Deviation 1.64 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 4 | Pain | -1.71 units on a scale | Standard Deviation 2.44 |
| Matching Placebo | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 4 | Distension | -1.70 units on a scale | Standard Deviation 1.6 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 4 | Abdominal Score | -1.91 units on a scale | Standard Deviation 1.39 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 4 | Abdominal Score + Distension | -1.74 units on a scale | Standard Deviation 1.37 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 4 | Distension | -1.22 units on a scale | Standard Deviation 1.69 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 4 | Pain | -1.90 units on a scale | Standard Deviation 1.5 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 4 | Discomfort | -2.24 units on a scale | Standard Deviation 1.92 |
| 290 μg Linaclotide | Change From Baseline of Symptom Severity (Abdominal Pain, Discomfort, Bloating, and Distension) at Week 4 | Bloating | -1.64 units on a scale | Standard Deviation 1.74 |
Secondary
Percent Change From Baseline in Maximal Abdominal Girth at Week 4
The maximum change in girth from the first hour, over the period from the 2nd hour to bedtime. The percentage change in maximum distension from baseline to 4 weeks will also be calculated.
Time frame: Baseline, Week 4
Population: Participants with an assessment at given time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Matching Placebo | Percent Change From Baseline in Maximal Abdominal Girth at Week 4 | -7.13 percent change | Standard Deviation 33.4 |
| 290 μg Linaclotide | Percent Change From Baseline in Maximal Abdominal Girth at Week 4 | 15.4 percent change | Standard Deviation 80.3 |