Irritable Bowel Syndrome With Constipation
Conditions
Brief summary
The primary purpose of this study is to evaluate the efficacy and safety of administration of lubiprostone in patients with irritable bowel syndrome with constipation.
Interventions
DRUGLubiprostone
DRUGPlacebo
Sponsors
Takeda
Sucampo Pharma Americas, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age and older * Stable fiber therapy * Normal colonoscopy/sigmoidoscopy * Able to refrain from use of medications known to treat or associated with constipation symptoms * Experiences abdominal discomfort/pain associated with bowel movements * Reports decreased bowel movement frequency and/or other symptoms associated with constipation
Exclusion criteria
* Diarrhea-predominant or alternating (diarrhea and constipation cycling) irritable bowel syndrome (IBS), or constipation other than that associated with IBS * Open gastrointestinal or abdominal surgery prior to IBS onset * Organic bowel disorder, mechanical bowel obstruction, pseudo-obstruction, unexplained weight loss or rectal bleeding * Uncontrolled cardiovascular, liver or lung disease, neurologic or psychiatric disorder, other systemic disease, or abnormal laboratory tests per investigator discretion * If female, is currently pregnant or nursing, or plans to become pregnant or nurse during the clinical study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Responder Rate | 12 weeks | Monthly responder: \>=Moderately relieved symptoms 4 weeks/month or Significantly relieved \>= 2 weeks/month IF: Rescue med use did not increase during the month; AND did not discontinue during the month for lack of efficacy; AND no Moderately worse or Significantly worse response in month. Overall responder: responder for at least 2/3 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Month 1 Stool Consistency Change From Baseline | Change from baseline for month 1 | 0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls) |
| Month 1 Bowel Straining Change From Baseline | Change from baseline for month 1 | 0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe |
| Month 1 Constipation Severity Change From Baseline | Change from baseline at 28 days | 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe |
| Month 1 Symptom Relief | Change from baseline for month 1 | Significantly worse = -3; Moderately worse = -2; A little bit worse = -1; Unchanged = 0; A little bit relieved=1; Moderately relieved=2; Significantly relieved = 3 |
| Quality of Life Change From Baseline | Change from baseline at 12 weeks | Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire included 34 questions with 5 possible responses yielding the following sub-categories: dysphoria, interference with activity, body image, health worry, food avoidance, social reaction, sexual, and relationship Results range from 34 (low) to 100 (high); meaningful clinical improvement=14 point increase |
| Month 2 Responder Rate | month 2 (28 days) | Monthly responder: \>=Moderately relieved symptoms 4 weeks/month or Significantly relieved \>= 2 weeks/month IF: Rescue med use did not increase during the month; AND did not discontinue during the month for lack of efficacy; AND no Moderately worse or Significantly worse response in month. |
| Month 3 Responder Rate | month 3 (28 days) | Symptoms \>= Moderately relieved for 4 weeks/month or Significantly relieved for \>=2 weeks/month AND: 1. Rescue medication use does not increase during the month as compared to baseline; 2. No discontinuation during the month due to lack of efficacy;AND 3. No ratings during the month of Moderately worse or Significantly worse. |
| Month 1 Responder Rate | month 1 (28 days) | Symptoms \>= Moderately relieved for 4 weeks/month or Significantly relieved for \>=2 weeks/month AND: 1. Rescue medication use does not increase during the month as compared to baseline; 2. No discontinuation during the month due to lack of efficacy;AND 3. No ratings during the month of Moderately worse or Significantly worse. |
| Month 2 Abdominal Bloating Change From Baseline | Change from baseline for month 2 | 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe |
| Month 3 Abdominal Bloating Change From Baseline | Change from baseline for month 3 | 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe |
| Month 2 Spontaneous Bowel Movement Frequency Rates Change From Baseline | Change from baseline for month 2 | Any bowel movement not associated with rescue medication use |
| Month 3 Spontaneous Bowel Movement Frequency Rates Change From Baseline | Change from baseline for month 3 | Any bowel movement not associated with rescue medication use |
| Month 2 Stool Consistency Change From Baseline | Change from baseline for month 2 | 0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls) |
| Month 1 Spontaneous Bowel Movement (SBM) Frequency Rates Change From Baseline | Change from baseline for month 1 | SBMs are any bowel movement not associated with rescue medication use. |
| Month 2 Bowel Straining Change From Baseline | Change from baseline for month 2 | 0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe |
| Month 3 Bowel Straining Change From Baseline | Change from baseline for month 3 | 0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe |
| Month 2 Constipation Severity Change From Baseline | Change from baseline for month 2 | 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe |
| Month 3 Constipation Severity Change From Baseline | Change from baseline for month 3 | 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe |
| Month 2 Symptom Relief | Change from baseline for month 2 | Significantly worse = -3; Moderately worse = -2; A little bit worse = -1; Unchanged = 0; A little bit relieved=1; Moderately relieved=2; Significantly relieved = 3 |
| Month 3 Symptom Relief | Change from baseline for month 3 | Significantly worse = -3; Moderately worse = -2; A little bit worse = -1; Unchanged = 0; A little bit relieved=1; Moderately relieved=2; Significantly relieved = 3 |
| Month 1 Abdominal Bloating Change From Baseline | Change from baseline for month 1 | 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe |
| Month 1 Bowel Movement Frequency Rates Change From Baseline | Change from baseline for month 1 | — |
| Month 2 Bowel Movement Frequency Rates Change From Baseline | Change from baseline for month 2 | — |
| Month 3 Bowel Movement Frequency Rates Change From Baseline | Change from baseline for month 3 | — |
| Month 1 Abdominal Pain Change From Baseline | Change from baseline for month 1 | 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe |
| Month 2 Abdominal Pain Change From Baseline | Change from baseline for month 2 | 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe |
| Month 3 Abdominal Pain Change From Baseline | Change from baseline for month 3 | 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe |
| Month 3 Stool Consistency Change From Baseline | Change from baseline for month 3 | 0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls) |
Participant flow
Recruitment details
First subject entered 5/12/05; Last subject observation 7/18/08; Multicenter study performed at 65 study sites/centers across the US
Pre-assignment details
Subjects were enrolled after an up to 4 week screening period to meet inclusion/exclusion criteria and randomized on Day 0
Participants by arm
| Arm | Count |
|---|---|
| Lubiprostone Study Period I Subjects who received active drug | 390 |
| Placebo Study Period I Subjects who received placebo | 193 |
| Total | 583 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 20 | 9 |
| Overall Study | Lack of Efficacy | 10 | 8 |
| Overall Study | Lost to Follow-up | 14 | 5 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 15 | 5 |
| Overall Study | Withdrawal by Subject | 39 | 28 |
Baseline characteristics
| Characteristic | Lubiprostone Study Period I | Placebo Study Period I | Total |
|---|---|---|---|
| Age, Continuous | 46.7 years | 48.1 years | 47.2 years |
| Height | 64.9 Inches STANDARD_DEVIATION 2.9 | 64.8 Inches STANDARD_DEVIATION 3.09 | 64.9 Inches STANDARD_DEVIATION 2.96 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 53 Participants | 29 Participants | 82 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 336 Participants | 160 Participants | 496 Participants |
| Sex: Female, Male Female | 355 Participants | 180 Participants | 535 Participants |
| Sex: Female, Male Male | 35 Participants | 13 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 75 / — | 25 / — |
| serious Total, serious adverse events | 5 / 396 | 2 / 192 |
Outcome results
Primary
Overall Responder Rate
Monthly responder: \>=Moderately relieved symptoms 4 weeks/month or Significantly relieved \>= 2 weeks/month IF: Rescue med use did not increase during the month; AND did not discontinue during the month for lack of efficacy; AND no Moderately worse or Significantly worse response in month. Overall responder: responder for at least 2/3 months
Time frame: 12 weeks
Population: Intent-to-treat (ITT) without Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lubiprostone Study Period I | Overall Responder Rate | 13.8 percentage of participants |
| Placebo Study Period I | Overall Responder Rate | 7.8 percentage of participants |
Comparison: 90% statistical power to detect 70.6% improvement in response with lubiprostonep-value: 0.029Cochran-Mantel-Haenszel
Secondary
Month 1 Abdominal Bloating Change From Baseline
0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time frame: Change from baseline for month 1
Population: ITT with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 1 Abdominal Bloating Change From Baseline | -0.30 Scale score | Standard Deviation 0.585 |
| Placebo Study Period I | Month 1 Abdominal Bloating Change From Baseline | -0.24 Scale score | Standard Deviation 0.516 |
p-value: 0.615van Elteren nonparametic test
Secondary
Month 1 Abdominal Pain Change From Baseline
0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time frame: Change from baseline for month 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 1 Abdominal Pain Change From Baseline | -0.29 Scale Score | Standard Deviation 0.588 |
| Placebo Study Period I | Month 1 Abdominal Pain Change From Baseline | -0.27 Scale Score | Standard Deviation 0.508 |
p-value: <0.001van Elteren nonparametric test
Secondary
Month 1 Bowel Movement Frequency Rates Change From Baseline
Time frame: Change from baseline for month 1
Population: ITT, with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 1 Bowel Movement Frequency Rates Change From Baseline | 1.22 BM/week | Standard Deviation 2.234 |
| Placebo Study Period I | Month 1 Bowel Movement Frequency Rates Change From Baseline | 0.88 BM/week | Standard Deviation 2.093 |
p-value: 0.108van Elteren nonparametric test
Secondary
Month 1 Bowel Straining Change From Baseline
0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time frame: Change from baseline for month 1
Population: ITT with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 1 Bowel Straining Change From Baseline | -0.53 Scale score | Standard Deviation 0.739 |
| Placebo Study Period I | Month 1 Bowel Straining Change From Baseline | -0.36 Scale score | Standard Deviation 0.694 |
p-value: 0.05van Elteren nonparametric test
Secondary
Month 1 Constipation Severity Change From Baseline
0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time frame: Change from baseline at 28 days
Population: ITT with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 1 Constipation Severity Change From Baseline | -0.41 Scale score | Standard Deviation 0.602 |
| Placebo Study Period I | Month 1 Constipation Severity Change From Baseline | -0.29 Scale score | Standard Deviation 0.568 |
p-value: 0.159van Elteren nonparametric test
Secondary
Month 1 Responder Rate
Symptoms \>= Moderately relieved for 4 weeks/month or Significantly relieved for \>=2 weeks/month AND: 1. Rescue medication use does not increase during the month as compared to baseline; 2. No discontinuation during the month due to lack of efficacy;AND 3. No ratings during the month of Moderately worse or Significantly worse.
Time frame: month 1 (28 days)
Population: ITT without LOCF
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lubiprostone Study Period I | Month 1 Responder Rate | 10.0 percent of participants |
| Placebo Study Period I | Month 1 Responder Rate | 6.2 percent of participants |
p-value: 0.098Cochran-Mantel-Haenszel
Secondary
Month 1 Spontaneous Bowel Movement (SBM) Frequency Rates Change From Baseline
SBMs are any bowel movement not associated with rescue medication use.
Time frame: Change from baseline for month 1
Population: ITT with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 1 Spontaneous Bowel Movement (SBM) Frequency Rates Change From Baseline | 1.54 SBM/week | Standard Deviation 2.462 |
| Placebo Study Period I | Month 1 Spontaneous Bowel Movement (SBM) Frequency Rates Change From Baseline | 1.21 SBM/week | Standard Deviation 2.286 |
p-value: 0.117van Elteren nonparametric test
Secondary
Month 1 Stool Consistency Change From Baseline
0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls)
Time frame: Change from baseline for month 1
Population: ITT with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 1 Stool Consistency Change From Baseline | -0.51 Scale score | Standard Deviation 0.69 |
| Placebo Study Period I | Month 1 Stool Consistency Change From Baseline | -0.33 Scale score | Standard Deviation 0.626 |
p-value: 0.006van Elteren nonparametric test
Secondary
Month 1 Symptom Relief
Significantly worse = -3; Moderately worse = -2; A little bit worse = -1; Unchanged = 0; A little bit relieved=1; Moderately relieved=2; Significantly relieved = 3
Time frame: Change from baseline for month 1
Population: ITT with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 1 Symptom Relief | 0.66 Scale score | Standard Deviation 1.212 |
| Placebo Study Period I | Month 1 Symptom Relief | 0.57 Scale score | Standard Deviation 1.088 |
p-value: 0.378Cochran-Mantel-Haenszel
Secondary
Month 2 Abdominal Bloating Change From Baseline
0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time frame: Change from baseline for month 2
Population: ITT with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 2 Abdominal Bloating Change From Baseline | -0.42 Scale score | Standard Deviation 0.693 |
| Placebo Study Period I | Month 2 Abdominal Bloating Change From Baseline | -0.35 Scale score | Standard Deviation 0.621 |
p-value: 0.286van Elteren nonparametric test
Secondary
Month 2 Abdominal Pain Change From Baseline
0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time frame: Change from baseline for month 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 2 Abdominal Pain Change From Baseline | -0.43 Scale Score | Standard Deviation 0.695 |
| Placebo Study Period I | Month 2 Abdominal Pain Change From Baseline | -0.37 Scale Score | Standard Deviation 0.614 |
p-value: <0.001van Elteren nonparametric test
Secondary
Month 2 Bowel Movement Frequency Rates Change From Baseline
Time frame: Change from baseline for month 2
Population: ITT, with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 2 Bowel Movement Frequency Rates Change From Baseline | 1.23 BM/week | Standard Deviation 2.44 |
| Placebo Study Period I | Month 2 Bowel Movement Frequency Rates Change From Baseline | 1.10 BM/week | Standard Deviation 2.581 |
p-value: 0.483van Elteren nonparametric test
Secondary
Month 2 Bowel Straining Change From Baseline
0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time frame: Change from baseline for month 2
Population: ITT with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 2 Bowel Straining Change From Baseline | -0.58 Scale score | Standard Deviation 0.846 |
| Placebo Study Period I | Month 2 Bowel Straining Change From Baseline | -0.43 Scale score | Standard Deviation 0.762 |
p-value: 0.049van Elteren nonparametric test
Secondary
Month 2 Constipation Severity Change From Baseline
0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time frame: Change from baseline for month 2
Population: ITT with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 2 Constipation Severity Change From Baseline | -0.50 Scale score | Standard Deviation 0.719 |
| Placebo Study Period I | Month 2 Constipation Severity Change From Baseline | -0.40 Scale score | Standard Deviation 0.67 |
p-value: 0.064van Elteren nonparametric test
Secondary
Month 2 Responder Rate
Monthly responder: \>=Moderately relieved symptoms 4 weeks/month or Significantly relieved \>= 2 weeks/month IF: Rescue med use did not increase during the month; AND did not discontinue during the month for lack of efficacy; AND no Moderately worse or Significantly worse response in month.
Time frame: month 2 (28 days)
Population: ITT without LOCF
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lubiprostone Study Period I | Month 2 Responder Rate | 15.9 percent of participants |
| Placebo Study Period I | Month 2 Responder Rate | 9.3 percent of participants |
p-value: 0.028Cochran-Mantel-Haenszel
Secondary
Month 2 Spontaneous Bowel Movement Frequency Rates Change From Baseline
Any bowel movement not associated with rescue medication use
Time frame: Change from baseline for month 2
Population: ITT with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 2 Spontaneous Bowel Movement Frequency Rates Change From Baseline | 1.59 SBM/week | Standard Deviation 2.795 |
| Placebo Study Period I | Month 2 Spontaneous Bowel Movement Frequency Rates Change From Baseline | 1.41 SBM/week | Standard Deviation 2.587 |
p-value: 0.334van Elteren nonparametric test
Secondary
Month 2 Stool Consistency Change From Baseline
0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls)
Time frame: Change from baseline for month 2
Population: ITT with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 2 Stool Consistency Change From Baseline | -0.53 Scale score | Standard Deviation 0.756 |
| Placebo Study Period I | Month 2 Stool Consistency Change From Baseline | -0.38 Scale score | Standard Deviation 0.658 |
p-value: 0.03van Elteren nonparametric test
Secondary
Month 2 Symptom Relief
Significantly worse = -3; Moderately worse = -2; A little bit worse = -1; Unchanged = 0; A little bit relieved=1; Moderately relieved=2; Significantly relieved = 3
Time frame: Change from baseline for month 2
Population: ITT with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 2 Symptom Relief | 0.76 Scale score | Standard Deviation 1.278 |
| Placebo Study Period I | Month 2 Symptom Relief | 0.59 Scale score | Standard Deviation 1.203 |
p-value: 0.144Cochran-Mantel-Haenszel
Secondary
Month 3 Abdominal Bloating Change From Baseline
0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time frame: Change from baseline for month 3
Population: ITT with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 3 Abdominal Bloating Change From Baseline | -0.43 Scale score | Standard Deviation 0.734 |
| Placebo Study Period I | Month 3 Abdominal Bloating Change From Baseline | -0.37 Scale score | Standard Deviation 0.693 |
p-value: 0.337van Elteren nonparametric test
Secondary
Month 3 Abdominal Pain Change From Baseline
0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time frame: Change from baseline for month 3
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 3 Abdominal Pain Change From Baseline | -0.42 Scale Score | Standard Deviation 0.722 |
| Placebo Study Period I | Month 3 Abdominal Pain Change From Baseline | -0.36 Scale Score | Standard Deviation 0.684 |
p-value: <0.001van Elteren nonparametric test
Secondary
Month 3 Bowel Movement Frequency Rates Change From Baseline
Time frame: Change from baseline for month 3
Population: ITT, with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 3 Bowel Movement Frequency Rates Change From Baseline | 1.15 BM/week | Standard Deviation 2.744 |
| Placebo Study Period I | Month 3 Bowel Movement Frequency Rates Change From Baseline | 1.04 BM/week | Standard Deviation 2.731 |
p-value: 0.491van Elteren nonparametric test
Secondary
Month 3 Bowel Straining Change From Baseline
0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time frame: Change from baseline for month 3
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 3 Bowel Straining Change From Baseline | -0.56 Scale score | Standard Deviation 0.847 |
| Placebo Study Period I | Month 3 Bowel Straining Change From Baseline | -0.45 Scale score | Standard Deviation 0.76 |
p-value: 0.348van Elteren nonparametric test
Secondary
Month 3 Constipation Severity Change From Baseline
0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe
Time frame: Change from baseline for month 3
Population: ITT with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 3 Constipation Severity Change From Baseline | -0.51 Scale score | Standard Deviation 0.755 |
| Placebo Study Period I | Month 3 Constipation Severity Change From Baseline | -0.41 Scale score | Standard Deviation 0.712 |
p-value: 0.111van Elteren nonparametric test
Secondary
Month 3 Responder Rate
Symptoms \>= Moderately relieved for 4 weeks/month or Significantly relieved for \>=2 weeks/month AND: 1. Rescue medication use does not increase during the month as compared to baseline; 2. No discontinuation during the month due to lack of efficacy;AND 3. No ratings during the month of Moderately worse or Significantly worse.
Time frame: month 3 (28 days)
Population: ITT without LOCF
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lubiprostone Study Period I | Month 3 Responder Rate | 15.9 percent of participants |
| Placebo Study Period I | Month 3 Responder Rate | 10.4 percent of participants |
p-value: 0.069Cochran-Mantel-Haenszel
Secondary
Month 3 Spontaneous Bowel Movement Frequency Rates Change From Baseline
Any bowel movement not associated with rescue medication use
Time frame: Change from baseline for month 3
Population: ITT with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 3 Spontaneous Bowel Movement Frequency Rates Change From Baseline | 1.51 SBM/week | Standard Deviation 2.99 |
| Placebo Study Period I | Month 3 Spontaneous Bowel Movement Frequency Rates Change From Baseline | 1.39 SBM/week | Standard Deviation 2.851 |
p-value: 0.242van Elteren nonparametric test
Secondary
Month 3 Stool Consistency Change From Baseline
0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls)
Time frame: Change from baseline for month 3
Population: ITT with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 3 Stool Consistency Change From Baseline | -0.52 Scale score | Standard Deviation 0.725 |
| Placebo Study Period I | Month 3 Stool Consistency Change From Baseline | -0.41 Scale score | Standard Deviation 0.696 |
p-value: 0.13van Elteren nonparametric test
Secondary
Month 3 Symptom Relief
Significantly worse = -3; Moderately worse = -2; A little bit worse = -1; Unchanged = 0; A little bit relieved=1; Moderately relieved=2; Significantly relieved = 3
Time frame: Change from baseline for month 3
Population: ITT with LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Month 3 Symptom Relief | 0.74 Scale score | Standard Deviation 1.259 |
| Placebo Study Period I | Month 3 Symptom Relief | 0.57 Scale score | Standard Deviation 1.277 |
p-value: 0.168Cochran-Mantel-Haenszel
Secondary
Quality of Life Change From Baseline
Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire included 34 questions with 5 possible responses yielding the following sub-categories: dysphoria, interference with activity, body image, health worry, food avoidance, social reaction, sexual, and relationship Results range from 34 (low) to 100 (high); meaningful clinical improvement=14 point increase
Time frame: Change from baseline at 12 weeks
Population: ITT without LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone Study Period I | Quality of Life Change From Baseline | 16.7 Scale score | Standard Deviation 17.36 |
| Placebo Study Period I | Quality of Life Change From Baseline | 16.8 Scale score | Standard Deviation 19.72 |
p-value: 0.588ANCOVA