A Study of Oral Methylnaltrexone (MNTX) for the Treatment of Opioid-Induced Constipation (OIC) in Participants With Chronic, Non-Malignant Pain

Study Overview
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Brief Summary
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MNTX 3201 is a Phase 3, international, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety and efficacy of oral MNTX for the treatment of opioid induced constipation in participants with chronic, non-malignant pain.

Official Title
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A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Oral Methylnaltrexone for the Treatment of Opioid-Induced Constipation in Subjects With Chronic, Non-Malignant Pain

Conditions
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Opioid-Induced Constipation

Intervention / Treatment
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* Drug: Methylnaltrexone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: History of chronic non-malignant pain (originating from a non-malignant source) with condition(s) underlying the chronic pain of greater than or equal to (≥) 2 months' duration before the screening visit. Taking oral, transdermal, intravenous (IV), or subcutaneous (SC) opioids for chronic non-malignant pain for ≥1 month. No known history of chronic constipation prior to the initiation of opioid therapy. Currently taking laxative therapy for ≥30 days and willing to discontinue all laxative therapy at the start of screening period and use only study-permitted rescue laxatives throughout the screening and double-blind treatment periods.. Key Exclusion Criteria: Prior treatment with oral MNTX. Prior treatment with SC MNTX within 30 days of screening. Women who are pregnant, breastfeeding, or plan to become pregnant during the study. Fecal incontinence, rectal prolapse, fecal ostomy or other clinically significant gastrointestinal disorders such as inflammatory bowel disease or clinically significant irritable bowel syndrome that would have made bowel movement assessment inaccurate. Current treatment with partial opioid agonists (for example; buprenorphine) or combination agonists/antagonists.

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 |
| --- | --- |
| Experimental: MNTX 150 mg<br>Participants will receive methylnaltrexone (MNTX) 150 milligrams (mg) (1 tablet of MNTX 150 mg and 2 matching placebo tablets) orally once daily (QD) for 28 days (4 weeks), then MNTX tablets at a dose as needed (PRN) for remaining 56 days (8 weeks). | Drug: Methylnaltrexone<br>* Methylnaltrexone will be administered as per the dose and schedule specified in the respective arms.<br>* Other names: Relistor;Drug: Placebo<br>* Placebo matching to methylnaltrexone will be administered as per the schedule specified in the respective arms.<br>|
| Experimental: MNTX 300 mg<br>Participants will receive MNTX 300 mg (2 tablets of MNTX 150 mg each and 1 matching placebo tablet) orally QD for 28 days (4 weeks), then MNTX tablets at a dose PRN for remaining 56 days (8 weeks). | Drug: Methylnaltrexone<br>* Methylnaltrexone will be administered as per the dose and schedule specified in the respective arms.<br>* Other names: Relistor;Drug: Placebo<br>* Placebo matching to methylnaltrexone will be administered as per the schedule specified in the respective arms.<br>|
| Experimental: MNTX 450 mg<br>Participants will receive MNTX 450 mg (3 tablets of MNTX 150 mg each) orally QD for 28 days (4 weeks), then MNTX tablets at a dose PRN for remaining 56 days (8 weeks). | Drug: Methylnaltrexone<br>* Methylnaltrexone will be administered as per the dose and schedule specified in the respective arms.<br>* Other names: Relistor;|
| Placebo Comparator: Placebo<br>Participants will receive 3 tablets of placebo matched to MNTX orally QD for 84 days (12 weeks). | Drug: Placebo<br>* Placebo matching to methylnaltrexone will be administered as per the schedule specified in the respective arms.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Percentage of Dosing Days That Resulted in Rescue-Free Bowel Movements (RFBMs) Within 4 Hours of Dosing During Weeks 1 to 4 | RFBM was defined as a bowel movement without laxative use within 24 hours prior to bowel movement. | Weeks 1 to 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Responded (Responder) to Study Drug During Weeks 1 to 4 | A responder was defined as at least 3 RFBMs/week, with an increase of at least 1 RFBM/week over baseline, for at least 3 out of the first 4 weeks of the treatment period. Weekly number of RFBMs were calculated as follows: 7 * total number of RFBMs in a week/all non-missing assessment days in the given week. Weekly number of RFBMs was set to missing for any week when a participant completed less than (<) 4 diary days in a week. A RFBM was a bowel movement without laxative use within 24 hrs prior to the bowel movement. | Weeks 1 to 4 | 
| Change in Weekly Number of RFBMs From Baseline Over the Entire First 4 Weeks (28 Days) of Dosing | Weekly number of RFBMs were calculated as follows: 7 * total number of RFBMs in a week/all non-missing assessment days in the given week. Weekly number of RFBMs was set to missing for any week when a participant completed less than (<) 4 diary days in a week. A RFBM was a bowel movement without laxative use within 24 hrs prior to the bowel movement. | Baseline, Weeks 1 to 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment of Opioid-Induced Constipation in Participants with Chronic, Non-Malignant Pain