Study Evaluating Long-Term Safety of MOA-728 in Participants With Opioid-Induced Constipation

An Open-Label Study to Evaluate the Long-Term Safety of Subcutaneous MOA-728 for Treatment of Opioid-Induced Constipation in Subjects With Nonmalignant Pain

This study is designed to evaluate the long-term safety and tolerability of the subcutaneous (SC) injection form of N-methylnaltrexone bromide (MOA-728) for the treatment of opioid-induced constipation in participants with nonmalignant pain. The study consists of a 2-week screening period, a 48-week open-label treatment period and a 2 week follow-up period. Participants will need to agree to self-administer SC injections, complete daily diaries, and check-in via a daily telephone call during the study.

Study Overview

• Status: Completed
• Conditions: Constipation
• Intervention / Treatment: Drug: N-methylnaltrexone bromide (MOA-728)

• Study Type: Interventional
• Enrollment (Actual): 1040
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Broadmeadow, New South Wales, Australia, 2292
      • Pfizer Investigational Site
• Canada
  • Quebec, Canada, G2B 5S1
    • Pfizer Investigational Site
  • Alberta
    • Edmonton, Alberta, Canada, T5A 4L8
      • Pfizer Investigational Site
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1Z9
      • Pfizer Investigational Site
    • Vancouver, British Columbia, Canada, V5Z 1K3
      • Pfizer Investigational Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2V 4W3
      • Pfizer Investigational Site
  • Newfoundland and Labrador
    • Mount Pearl, Newfoundland and Labrador, Canada, A1N 5B6
      • Pfizer Investigational Site
  • Nova Scotia
    • Dartmouth, Nova Scotia, Canada, B2Y 1H3
      • Pfizer Investigational Site
  • Ontario
    • Hamilton, Ontario, Canada, L8M 1K7
      • Pfizer Investigational Site
    • London, Ontario, Canada, N5Y 5K7
      • Pfizer Investigational Site
    • Oshawa, Ontario, Canada, L1H 7K4
      • Pfizer Investigational Site
    • Sarnia, Ontario, Canada, N7T 4X3
      • Pfizer Investigational Site
    • Toronto, Ontario, Canada, M9W 4L6
      • Pfizer Investigational Site
  • Quebec
    • Mirabel, Quebec, Canada, J7J 2K8
      • Pfizer Investigational Site
    • Sainte-Foy, Quebec, Canada, G1W 4R4
      • Pfizer Investigational Site
    • Sherbrooke, Quebec, Canada, J1H 1Z1
      • Pfizer Investigational Site
    • St-Romuald, Quebec, Canada, G6W 5M6
      • Pfizer Investigational Site
    • Trois-Rivieres, Quebec, Canada, G8T 7A1
      • Pfizer Investigational Site
• Colombia
  • Atlantico
    • Barranquilla, Atlantico, Colombia
      • Pfizer Investigational Site
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia
      • Pfizer Investigational Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 137-701
    • Pfizer Investigational Site
  • Kyonggi-do
    • Suwon, Kyonggi-do, Korea, Republic of, 443-721
      • Pfizer Investigational Site
  • Seoul/Korea
    • Seoul, Seoul/Korea, Korea, Republic of, 138-736
      • Pfizer Investigational Site
• Spain
  • Barcelona/Spain
    • Badalona, Barcelona/Spain, Spain, 08916
      • Pfizer Investigational Site
  • Madrid/Spain
    • Madrid, Madrid/Spain, Spain, 28006
      • Pfizer Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35242
      • Pfizer Investigational Site
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Pfizer Investigational Site
    • Mesa, Arizona, United States, 85206
      • Pfizer Investigational Site
    • Mesa, Arizona, United States, 85213
      • Pfizer Investigational Site
    • Phoenix, Arizona, United States, 85028
      • Pfizer Investigational Site
    • Phoenix, Arizona, United States, 85029
      • Pfizer Investigational Site
    • Tempe, Arizona, United States, 85282
      • Pfizer Investigational Site
    • Tucson, Arizona, United States, 85741
      • Pfizer Investigational Site
    • Tucson, Arizona, United States, 85710
      • Pfizer Investigational Site
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Pfizer Investigational Site
  • California
    • Garden Grove, California, United States, 92843
      • Pfizer Investigational Site
    • Laguna Hills, California, United States, 92653
      • Pfizer Investigational Site
    • Los Gatos, California, United States, 95032
      • Pfizer Investigational Site
    • Newport Beach, California, United States, 92660
      • Pfizer Investigational Site
    • Newport Beach, California, United States, 92663
      • Pfizer Investigational Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80904
      • Pfizer Investigational Site
  • Florida
    • Boca Raton, Florida, United States, 33432
      • Pfizer Investigational Site
    • Brandon, Florida, United States, 33511
      • Pfizer Investigational Site
    • Chiefland, Florida, United States, 32626
      • Pfizer Investigational Site
    • Clearwater, Florida, United States, 33756
      • Pfizer Investigational Site
    • Daytona Beach, Florida, United States, 32117
      • Pfizer Investigational Site
    • Fort Myers, Florida, United States, 33916
      • Pfizer Investigational Site
    • Gainesville, Florida, United States, 32607
      • Pfizer Investigational Site
    • Jacksonville, Florida, United States, 32216
      • Pfizer Investigational Site
    • Jacksonville, Florida, United States, 32257
      • Pfizer Investigational Site
    • Jupiter, Florida, United States, 33458
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33180
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33183
      • Pfizer Investigational Site
    • Ocala, Florida, United States, 34471
      • Pfizer Investigational Site
    • Ocala, Florida, United States, 34474
      • Pfizer Investigational Site
    • Ocala, Florida, United States, 34471-2106
      • Pfizer Investigational Site
    • Orlando, Florida, United States, 32806
      • Pfizer Investigational Site
    • Ormond Beach, Florida, United States, 32174
      • Pfizer Investigational Site
    • Port Orange, Florida, United States, 32129
      • Pfizer Investigational Site
    • Sarasota, Florida, United States, 34239
      • Pfizer Investigational Site
    • Sarasota, Florida, United States, 34231
      • Pfizer Investigational Site
    • Tampa, Florida, United States, 33603
      • Pfizer Investigational Site
    • Tampa, Florida, United States, 33613
      • Pfizer Investigational Site
    • Vero Beach, Florida, United States, 32960
      • Pfizer Investigational Site
    • Winter Park, Florida, United States, 32789
      • Pfizer Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60616
      • Pfizer Investigational Site
    • Rockford, Illinois, United States, 61107
      • Pfizer Investigational Site
  • Indiana
    • Avon, Indiana, United States, 46123
      • Pfizer Investigational Site
    • Evansville, Indiana, United States, 47714
      • Pfizer Investigational Site
    • Indianapolis, Indiana, United States, 46250
      • Pfizer Investigational Site
    • Indianapolis, Indiana, United States, 46205
      • Pfizer Investigational Site
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Pfizer Investigational Site
  • Kentucky
    • Madisonville, Kentucky, United States, 42431
      • Pfizer Investigational Site
  • Maryland
    • Hagerstown, Maryland, United States, 21742
      • Pfizer Investigational Site
    • Hollywood, Maryland, United States, 20636
      • Pfizer Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Pfizer Investigational Site
    • Brockton, Massachusetts, United States, 02301
      • Pfizer Investigational Site
    • Watertown, Massachusetts, United States, 02472
      • Pfizer Investigational Site
  • Michigan
    • Bingham Farms, Michigan, United States, 48025
      • Pfizer Investigational Site
    • Chesterfield, Michigan, United States, 48047
      • Pfizer Investigational Site
    • Kalamazoo, Michigan, United States, 49009
      • Pfizer Investigational Site
    • Traverse City, Michigan, United States, 49684
      • Pfizer Investigational Site
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Pfizer Investigational Site
  • Mississippi
    • Biloxi, Mississippi, United States, 39531
      • Pfizer Investigational Site
    • Jackson, Mississippi, United States, 39202
      • Pfizer Investigational Site
  • Missouri
    • Springfield, Missouri, United States, 65807
      • Pfizer Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Pfizer Investigational Site
  • Nevada
    • Henderson, Nevada, United States, 89014
      • Pfizer Investigational Site
    • Las Vegas, Nevada, United States, 89146
      • Pfizer Investigational Site
    • Las Vegas, Nevada, United States, 89123
      • Pfizer Investigational Site
    • Las Vegas, Nevada, United States, 89119
      • Pfizer Investigational Site
  • New Jersey
    • Elizabeth, New Jersey, United States, 07202
      • Pfizer Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Pfizer Investigational Site
  • New York
    • Great Neck, New York, United States, 11023
      • Pfizer Investigational Site
    • New York, New York, United States, 10022
      • Pfizer Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Pfizer Investigational Site
    • Raleigh, North Carolina, United States, 27607
      • Pfizer Investigational Site
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Pfizer Investigational Site
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Pfizer Investigational Site
    • Dayton, Ohio, United States, 45432
      • Pfizer Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Pfizer Investigational Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • Pfizer Investigational Site
    • Portland, Oregon, United States, 97210
      • Pfizer Investigational Site
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • Pfizer Investigational Site
    • Levittown, Pennsylvania, United States, 19056
      • Pfizer Investigational Site
    • Yardley, Pennsylvania, United States, 19067
      • Pfizer Investigational Site
  • Rhode Island
    • Cranston, Rhode Island, United States, 02920
      • Pfizer Investigational Site
  • Tennessee
    • Huntingdon, Tennessee, United States, 38344
      • Pfizer Investigational Site
  • Texas
    • Austin, Texas, United States, 78705
      • Pfizer Investigational Site
    • Beaumont, Texas, United States, 77701
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75234
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75230
      • Pfizer Investigational Site
    • Houston, Texas, United States, 77074
      • Pfizer Investigational Site
    • Hurst, Texas, United States, 76054
      • Pfizer Investigational Site
    • San Antonio, Texas, United States, 78229
      • Pfizer Investigational Site
    • San Antonio, Texas, United States, 78215
      • Pfizer Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Pfizer Investigational Site
  • Virginia
    • Christiansburg, Virginia, United States, 24073
      • Pfizer Investigational Site
  • Washington
    • Bellevue, Washington, United States, 98007
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women 18 years or older.
• A history of pain of at least 2 months duration before the screening visit due to documented underlying nonmalignant condition.
• A history of constipation due to opioid use during 1 month before the screening visit.

Exclusion Criteria:

• A diagnosis of significant gastrointestinal (GI) disorder such as bowel obstruction, fecal incontinence or rectal prolapse.
• A history of active inflammatory bowel disease, irritable bowel syndrome, or megacolon within 6 months before the screening visit.
• A history of malignancy, other than basal cell or squamous cell skin carcinoma, within 5 years before the screening visit.
• A history of chronic constipation before initiation of opioid therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MOA-728 12 mg QD; Participants will receive MOA-728 12 milligrams (mg) SC once daily (QD) for 48 weeks. Dosing could be adjusted to an as needed (PRN) basis with a minimum 1 dose per week and maximum 1 dose per day.	Drug: N-methylnaltrexone bromide (MOA-728); MOA-728 will be administered as per the dose and schedule specified in the arm.; Other Names: Relistor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Serious adverse events (SAEs) included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as an AE that emerged during the treatment period. Any TEAEs included both treatment-emergent SAEs and non-serious AEs. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.	Baseline up to Week 50

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weekly Bowel Movement (BM) Rate Through Follow-up	Weekly BM rate was derived as the total number of BMs reported in a month divided by the total number of days with non-missing BM diary information in the same month, then multiplied by 7 to normalize to a weekly rate. If the total number of days with non-missing BM diary information in a given month was less than 10 days, the weekly BM rate for the month was defined as missing. The weekly BM rate at baseline was calculated based on the screening period (Days -14 to -1). If the total number of days with non-missing BM diary information during the screening period was less than 5 days, the weekly BM rate at baseline was defined as missing.	Baseline, follow-up (14 days [Week 49 to 50])

Collaborators and Investigators

• Sponsor: Bausch Health Americas, Inc.
• Collaborators: Pfizer

Publications and helpful links

General Publications

• Michna E, Blonsky ER, Schulman S, Tzanis E, Manley A, Zhang H, Iyer S, Randazzo B. Subcutaneous methylnaltrexone for treatment of opioid-induced constipation in patients with chronic, nonmalignant pain: a randomized controlled study. J Pain. 2011 May;12(5):554-62. doi: 10.1016/j.jpain.2010.11.008. Epub 2011 Mar 22.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2008
• Primary Completion (Actual): September 20, 2010
• Study Completion (Actual): September 20, 2010

Study Registration Dates

• First Submitted: December 5, 2008
• First Submitted That Met QC Criteria: December 5, 2008
• First Posted (Estimate): December 8, 2008

Study Record Updates

• Last Update Posted (Actual): October 18, 2019
• Last Update Submitted That Met QC Criteria: September 27, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: treatment for opioid-induced constipation
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Signs and Symptoms, Digestive; Narcotic-Related Disorders; Constipation; Opioid-Induced Constipation; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Anticonvulsants; Bromides; Methylnaltrexone
• Other Study ID Numbers: 3200K1-3358