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.

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 (OBD) 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 inhibitor (SSRIs), Serotonin-norepinephrine reuptake inhibitor (SNRIs), or Monoamine oxidase inhibitor (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: 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). Opioid dose adjustment (+/- 30%), and/or change in opioid agent or route of administration within 30 days of screening. Gastrointestinal or abdominal surgical procedures within 90 days prior to screening. Non-ambulatory patients, or those who are unable to eat/drink, take oral medications, or to hold down oral medications due to vomiting. 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. Prior use of Amitiza, lubiprostone, SPI-0211, or RU-0211.

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 |
| --- | --- | --- |
| Mean Weekly Spontaneous Bowel Movements at Week 8 | Spontaneous bowel movements (SBMs) are defined as bowel movements without the aid of drugs. | at Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Number of Spontaneous Bowel Movements (SBM) Per Week Within 12 Weeks | Average weekly SBM frequency was calculated from data collected from Week 1 through Week 12 | within 12 weeks | 
| Number of Participants With the First Post-dose Spontaneous Bowel Movement Within 48 Hours Post-dose | The number of participants who experienced their first post-dose Spontaneous Bowel Movement within 24 and 48 hours after dosing started. | within 48 hours post-dose | 
| Number of Participants Classified as Responders | Number of participants who remained on treatment for at least 8 weeks, and reported at least 3 SBMs for at least half the weeks on study. | within 12 weeks | 
| Mean Change From Baseline in Straining, Stool Consistency, Constipation Severity, Abdominal Bloating, Abdominal Discomfort, and Bowel Habit Regularity | Measures collected over 12-week treatment period were averaged, and the score at baseline was subtracted from the score at week 12 to determine the change from baseline. Straining scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe - higher scores are worse; Stool consistency scale: 0 = very loose, 1 = loose, 2 = normal, 3 = hard, 4 = very hard (little balls) - middle scores are best; Constipation severity scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe - higher scores are worse; Abdominal bloating scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe - higher scores are worse; Abdominal discomfort scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe - higher scores are worse; Bowel habit regularity scale: 7-point scale, where 1 = very regular and 7 = very irregular - higher scores are worse | within 12 weeks | 
| Participant Reported Outcome of Treatment Effectiveness | Participants rated treatment effectiveness at the end of each treatment week during the study on a 5-point scale, where 0 = not at all effective, 1 = a little bit effective, 2 = moderately effective, 3 = quite a bit effective, 4 = extremely effective. The 12 weekly scores were averaged. Higher scores mean the drug was more effective. | within 12 weeks |