Study Evaluating Subcutaneous MOA-728 for the Treatment of Opioid-Induced Constipation (OIC) in Subjects With Chronic Non-Malignant Pain

Study Overview
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Brief Summary
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The primary purpose of the protocol is to evaluate the safety, efficacy, and tolerability of subcutaneous MOA-728 versus placebo in subjects with chronic non-malignant pain who have Opioid-Induced Constipation (OIC).

Official Title
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A Mulitcenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Subcutaneous MOA-728 for the Treatment of Opioid-Induced Constipation in Subjects With Chronic Non-Malignant Pain

Conditions
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Constipation

Intervention / Treatment
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* Drug: N-methylnaltrexone bromide (MOA-728)
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult outpatients with opioid-induced constipation and chronic non-malignant pain. Taking oral, transdermal, intravenous, or subcutaneous opioids. Willingness to discontinue all pre-study laxative therapy and use only study permitted rescue laxatives. Exclusion Criteria History of chronic constipation before the initiation of opioid therapy. Other GI disorders known to affect bowel transit. Women who are pregnant, breast-feeding, or plan to become pregnant.

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: 1<br> | Other: placebo<br>* placebo<br>|
| Experimental: 2<br> | Drug: N-methylnaltrexone bromide (MOA-728)<br>* Subcutaneous<br>|
| Experimental: 3<br> | Drug: N-methylnaltrexone bromide (MOA-728)<br>* Subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Having a Rescue-free Bowel Movement (RFBM) Within 4 Hours of the First Dose | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). | up to 4 hours | 
| Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 4 Hours of Injection During the Double-blind Period | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). Active injections are those that contain study drug (e.g., daily injections in MOA-728 QD treatment group and every other injection for the MOA-728 QOD treatment group). The corresponding injections in the placebo group were used as controls. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the First Rescue-free Bowel Movement (RFBM) After First Dose | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). Responses following first injection were censored at 24 hours or at time of the second injection, which ever occurred first. | up to 24 hours | 
| Change From Baseline in Weekly Number of Rescue-free Bowel Movements (RFBM) for the Double-blind Period at 4 Weeks | A rescue-free bowel movement defined as a bowel movement with no laxatives use during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were reported daily by patient using a telephone interactive voice response system (IVRS). The weekly number of RFBM was defined as the total number of RFBM reported during the double-blind period divided by the number of days the patient reported diary information in that period, and then multiplied by 7 to normalize to a weekly number. | Baseline and 4 weeks | 
| Weekly Number of Rescue-free Bowel Movements (RFBM) (Open-label Period) | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone IVRS. The weekly number of RFBM was defined as the total number of RFBMs reported during study period divided by the number of days the patient reported diary information in that period, and then multiplied by 7 to normalize to a weekly number. Weekly number of RFBM determined as missing for <4 days of information. | 8 weeks | 
| Percentage of Patients Achieving at Least 3 Rescue-free Bowel Movements (RFBM) Per Week in Double-blind Period | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone IVRS. The weekly number of RFBM was defined as the total number of RFBM reported during the study week divided by the number of days the patient reported diary information in that period, and then multiplied by 7 to normalize to a weekly number. | 4 weeks | 
| Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). Active injections are those that contain study drug (e.g., daily injections in MOA-728 QD treatment group and every other injection for the MOA-728 QOD treatment group). The corresponding injections in the placebo group were used as controls. | Within 1-6 hours during 4 week double-blind period | 
| Percentage of Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3, 4 and 6 Hours in Double-blind Period | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). | Within 1-6 hours during 4-week double-blind period | 
| Percentage of Patients With a Weekly Rescue-free Bowel Movement (RFBM) Rate ≥ 3 and an Increase of at Least 1 in the Weekly RFBM Rate From Baseline for the Double-blind Period | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone IVRS. The weekly RFBM rate was defined as the total number of RFBM reported during study period divided by the number of days the subject reported diary information in that period, and then multiplied by 7 to normalize to a weekly rate. | 4 weeks | 
| Percentage of Patients With an Increase of at Least 1 in the Weekly Rescue-free Bowel Movement (RFBM) Rate From Baseline for the Double-blind Period at 4 Weeks | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone IVRS. The weekly RFBM rate was defined as the total number of RFBM reported during study period divided by the number of days the subject reported diary information in that period, and then multiplied by 7 to normalize to a weekly rate. | Baseline and 4 weeks | 
| Change in Weekly Number of Bowel Movements During Double-blind Period | Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The weekly number of BM was defined as the total number of BMs reported during study period divided by the number of days the subject reported diary information in that period, and then multiplied by 7 to normalize to a weekly number. | 4 weeks | 
| Change From Baseline in Weekly Number of Quality Rescue-free Bowel Movements (RFBM) | RFBM defined as bowel movement with no laxatives during the prior 24 hours. Information on laxative use, bowel movements and assessments were reported daily by patient. Weekly number of quality RFBM was the total number of quality RFBM reported in study period divided by number of days with information and multiplied by 7 for a normalized weekly number. Stool quality assessed with the Bristol Stool Form Scale (7-points) (1=difficult to pass, 7=entirely liquid). A quality RFBM defined as one other than diarrhea (Bristol Type 1-5). | 4 weeks | 
| Change in Weekly Number of Complete Rescue-free Bowel Movements (RFBM) | A rescue-free bowel movement defined as a bowel movement with no laxatives use during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were reported daily by patient using a telephone interactive voice response system (IVRS). Weekly number of complete RFBM was the total number of complete RFBM reported in study period divided by the number of days with information, and multiplied by 7 for a normalized weekly number. A complete RFBM has a sensation of complete evacuation. | 4 weeks | 
| Change in Bristol Stool Form Scale Score for Rescue-free Bowel Movements (RFBM) | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The Bristol Stool Form Scale assessed stool quality using a 7-point scale, where Type 1 = separate hard lumps like nuts (difficult to pass) and Type 7 = watery, no solid pieces (entirely liquid.) | 4 weeks | 
| Change in Straining Scale Score of Rescue-free Bowel Movements (RFBM) From Baseline During Double-blind Period | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The amount of straining associated with bowel movements was assessed using a 5-point straining scale, where 0=none and 4=very severe. | 4 weeks | 
| Percentage of Patients With Improvement in Bristol Stool Form Scale Score for Rescue-free Bowel Movements (RFBM) by 1 Point During Open Label Period | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The Bristol Stool Form Scale assessed stool quality using a 7-point scale, where Type 1 = separate hard lumps like nuts (difficult to pass) and Type 7 = watery, no solid pieces (entirely liquid.) | 8 weeks | 
| Percentage of Patients With Improvement in Straining Scale Score for Rescue-free Bowel Movements (RFBM) by 1 Point During Open Label Period | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The amount of straining associated with bowel movements was assessed using a 5-point straining scale, where 0=none and 4=very severe. | 8 weeks | 
| Change in Percentage of Rescue-free Bowel Movements (RFBM) With Bristol Stool Form Scale in Type 3 or Type 4 From Baseline During Double-blind Period | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone IVRS. The Bristol Stool Form Scale assessed stool quality using a 7-point scale, where Type 1=separate hard lumps like nuts (difficult to pass) and Type 7=watery, no solid pieces (entirely liquid.) Specifically, Type 3=like a sausage but with cracks on the surface, Type 4=Like a sausage or snake, smooth and soft. | 4 weeks | 
| Change in Percentage of Rescue-free Bowel Movements (RFBM) Classified as Diarrhea or Watery Stools From Baseline During Double-blind Period | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The Bristol Stool Form Scale assessed stool quality using a 7-point scale, where Type 1 = separate hard lumps like nuts (difficult to pass), Type 6 = fluffy pieces with ragged edges, a mushy stool, and Type 7 = watery, no solid pieces (entirely liquid.) This analysis included types 6 and 7. | 4 weeks | 
| Percentage of Patients With Any Diarrhea or Watery Rescue-free Bowel Movements (RFBM) During Open-label Period. | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The Bristol Stool Form Scale assessed stool quality using a 7-point scale, where Type 1 = separate hard lumps like nuts (difficult to pass), Type 6 = fluffy pieces with ragged edges, a mushy stool, and Type 7 = watery, no solid pieces (entirely liquid.) This analysis included types 6 and 7. | weeks 5-12 | 
| Change in Percentage of Rescue-free Bowel Movements (RFBM) With Straining Scale Scores of 0 or 1 (no, or Mild) From Baseline During Double-blind Period | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). The amount of straining associated with bowel movements was assessed using a 5-point straining scale, where 0=none, 1 = mild and 4=very severe. | 4 weeks | 
| Change in Percentage of Rescue-free Bowel Movements (RFBM) With a Sensation of Complete Evacuation From Baseline During Double-blind Period | A rescue-free bowel movement was defined as a bowel movement where no laxatives were used during the prior 24 hours. Information on laxative use, bowel movements and bowel movement assessments were self reported daily by the patient using a telephone interactive voice response system (IVRS). A complete RFBM has a sensation of complete evacuation. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opioid-Induced Constipation