Efficacy and Safety of Lubiprostone in Patients With Irritable Bowel Syndrome With Constipation

Study Overview
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Brief Summary
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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.

Official Title
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Phase 3, 12-Week, Multicenter, Double-Blind, Randomized, Efficacy and Safety Study of Lubiprostone for the Treatment of Irritable Bowel Syndrome With Constipation

Conditions
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Irritable Bowel Syndrome With Constipation

Intervention / Treatment
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* Drug: Lubiprostone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lubiprostone<br>8 mcg capsule twice daily (BID) | Drug: Lubiprostone<br> <br> |
| Placebo Comparator: Placebo<br>Matching placebo capsule twice daily (BID) | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Month 1 Spontaneous Bowel Movement (SBM) Frequency Rates Change From Baseline | SBMs are any bowel movement not associated with rescue medication use. | Change from baseline for month 1 | 
| Month 1 Stool Consistency Change From Baseline | 0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls) | Change from baseline for month 1 | 
| Month 1 Bowel Straining Change From Baseline | 0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe | Change from baseline for month 1 | 
| Month 1 Constipation Severity Change From Baseline | 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe | Change from baseline at 28 days | 
| 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 | Change from baseline for month 1 | 
| 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 | Change from baseline at 12 weeks | 
| 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. | month 2 (28 days) | 
| Month 3 Responder Rate | Symptoms >= Moderately relieved for 4 weeks/month or Significantly relieved for >=2 weeks/month AND: Rescue medication use does not increase during the month as compared to baseline; No discontinuation during the month due to lack of efficacy;AND No ratings during the month of Moderately worse or Significantly worse. | month 3 (28 days) | 
| Month 1 Responder Rate | Symptoms >= Moderately relieved for 4 weeks/month or Significantly relieved for >=2 weeks/month AND: Rescue medication use does not increase during the month as compared to baseline; No discontinuation during the month due to lack of efficacy;AND No ratings during the month of Moderately worse or Significantly worse. | month 1 (28 days) | 
| Month 2 Abdominal Bloating Change From Baseline | 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe | Change from baseline for month 2 | 
| Month 3 Abdominal Bloating Change From Baseline | 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe | Change from baseline for month 3 | 
| Month 2 Spontaneous Bowel Movement Frequency Rates Change From Baseline | Any bowel movement not associated with rescue medication use | Change from baseline for month 2 | 
| Month 3 Spontaneous Bowel Movement Frequency Rates Change From Baseline | Any bowel movement not associated with rescue medication use | Change from baseline for month 3 | 
| Month 2 Stool Consistency Change From Baseline | 0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls) | Change from baseline for month 2 | 
| Month 3 Stool Consistency Change From Baseline | 0 = Very loose (watery), 1 = Loose, 2 = Normal, 3 = Hard, 4 = Very hard (little balls) | Change from baseline for month 3 | 
| Month 2 Bowel Straining Change From Baseline | 0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe | Change from baseline for month 2 | 
| Month 3 Bowel Straining Change From Baseline | 0 = Absent,1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe | Change from baseline for month 3 | 
| Month 2 Constipation Severity Change From Baseline | 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe | Change from baseline for month 2 | 
| Month 3 Constipation Severity Change From Baseline | 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe | Change from baseline for month 3 | 
| 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 | Change from baseline for month 2 | 
| 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 | Change from baseline for month 3 | 
| Month 1 Abdominal Bloating Change From Baseline | 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe | Change from baseline for month 1 | 
| 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 | 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe | Change from baseline for month 1 | 
| Month 2 Abdominal Pain Change From Baseline | 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe | Change from baseline for month 2 | 
| Month 3 Abdominal Pain Change From Baseline | 0 = Absent, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very Severe | Change from baseline for month 3 |