Opioid-induced Bowel Dysfunction Pivotal Assessment of Lubiprostone

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 lubiprostone administration in patients with opioid-induced bowel dysfunction (OBD).

Official Title
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A Multi-center, Randomized, Double-Blinded Study of the Efficacy and Safety of Lubiprostone in Patients With Opioid-induced Bowel Dysfunction (OBD)

Conditions
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Opioid-Induced Bowel Dysfunction

Intervention / Treatment
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* Drug: Lubiprostone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consistent treatment for chronic, non-cancer-related pain with any full agonist opioid for at least 30 days prior to screening. Diagnosis of opioid-induced bowel dysfunction as confirmed during the screening period. If patient has a history of chronic constipation, condition must have been exacerbated by initiation of opioid treatment. Use of prescribed or over-the-counter (OTC) medication that affects gastrointestinal motility (other than opioid therapy) must be discontinued during the study. If treated for clinical depression with selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or monoamine oxidase (MAO) inhibitors, treatment must have been at a stable dose for at least 30 days prior to screening. Use of laxative and stool softeners (with the exception of approved rescue medications) must be discontinued while on study. Exclusion Criteria: Opioid dose adjustment (+/- 30%), and/or change in opioid agent or route of administration within 30 days of screening. Non-ambulatory patients, or those who are unable to eat/drink, take oral medications, or to hold down oral medications due to vomiting. Treatment with opioid therapy for cancer-related pain, abdominal pain, scleroderma, and/or for the management of drug addiction. Patient has been treated for cancer in the past 5 years (with the exception of localized basal cell, squamous cell skin cancer, or in situ cancer that has been resected). Gastrointestinal or abdominal surgical procedures within 90 days prior to screening. Female patients of childbearing potential who are unable/unwilling to use protocol-specified method(s) of birth control and/or are pregnant, nursing, or plan to become pregnant or nurse during the 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>0 mcg capsules twice daily (BID) | Drug: Placebo<br>* 0 mcg capsules twice daily (BID)<br>* Other names: No other names;|
| Experimental: Lubiprostone<br>24 mcg capsules twice daily (BID) | Drug: Lubiprostone<br>* 24 mcg capsules twice daily (BID)<br>* Other names: Amitiza®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Weekly Spontaneous Bowel Movement (SBM) Frequency in Subjects Without Dose Reduction Prior to Week 8 |  | Baseline and Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Weekly SBM Frequency | For overall assessment of change, average weekly rating was calculated from data collected from Week 1 through Week 12. | Baseline, Week 12, and Weeks 1-12 | 
| First Post-dose SBM | The number of participants that experienced first post-dose SBM 24 and 48 hour of dose initiation. | 24 and 48 hours post-dose | 
| Responder Rate | Number of participants, who remained on treatment for at least 8 weeks, and reported response (>=3 SBMs) for at least 50% of weeks on study. | Up to 12 weeks | 
| Mean Changes From Baseline in Straining, Stool Consistency, Constipation Severity, Abdominal Bloating, Abdominal Discomfort, and Bowel Habit Regularity | Ratings over 12-week treatment period were averaged and difference from baseline score calculated Straining scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe Stool consistency scale: 0 = very loose, 1 = loose, 2 = normal, 3 = hard, 4 = very hard (little balls) Constipation severity scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe Abdominal bloating scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe Abdominal discomfort scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe Bowel habit regularity scale: 7-point scale, where 1 = very regular and 7 = very irregular | Weeks 1-12 | 
| Treatment Effectiveness | Treatment effectiveness scale: 0 = not at all effective, 1 = a little bit effective, 2 = moderately effective, 3 = quite a bit effective, 4 = extremely effective | Weeks 1-12 |