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

This study has been completed.
Sponsor:
Collaborator:
Progenics Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Salix Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00529087
First received: September 11, 2007
Last updated: September 7, 2011
Last verified: September 2011
History of Changes
  Purpose

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).


Condition Intervention Phase
Constipation
 Drug: N-methylnaltrexone bromide (MOA-728)
Other: placebo
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Salix Pharmaceuticals:

Primary Outcome Measures:
  • Percentage of Patients Having a Rescue-free Bowel Movement (RFBM) Within 4 Hours of the First Dose [ Time Frame: up to 4 hours ] [ Designated as safety issue: No ]
    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).

  • Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 4 Hours of Injection During the Double-blind Period [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Time to the First Rescue-free Bowel Movement (RFBM) After First Dose [ Time Frame: up to 24 hours ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Weekly Number of Rescue-free Bowel Movements (RFBM) for the Double-blind Period at 4 Weeks [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    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.

  • Weekly Number of Rescue-free Bowel Movements (RFBM) (Open-label Period) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Percentage of Patients Achieving at Least 3 Rescue-free Bowel Movements (RFBM) Per Week in Double-blind Period [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.

  • Percentage of Active Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3 and 6 Hour(s) in Double-blind Period [ Time Frame: Within 1-6 hours during 4 week double-blind period ] [ Designated as safety issue: No ]
    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.

  • Percentage of Injections Resulting in Any Rescue-free Bowel Movement (RFBM) Within 1, 2, 3, 4 and 6 Hours in Double-blind Period [ Time Frame: Within 1-6 hours during 4-week double-blind period ] [ Designated as safety issue: No ]
    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).

  • 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 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    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.

  • Change in Weekly Number of Bowel Movements During Double-blind Period [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Weekly Number of Quality Rescue-free Bowel Movements (RFBM) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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).

  • Change in Weekly Number of Complete Rescue-free Bowel Movements (RFBM) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.

  • Change in Bristol Stool Form Scale Score for Rescue-free Bowel Movements (RFBM) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.)

  • Change in Straining Scale Score of Rescue-free Bowel Movements (RFBM) From Baseline During Double-blind Period [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.

  • Percentage of Patients With Improvement in Bristol Stool Form Scale Score for Rescue-free Bowel Movements (RFBM) by 1 Point During Open Label Period [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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.)

  • Percentage of Patients With Improvement in Straining Scale Score for Rescue-free Bowel Movements (RFBM) by 1 Point During Open Label Period [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.

  • Change in Percentage of Rescue-free Bowel Movements (RFBM) Classified as Diarrhea or Watery Stools From Baseline During Double-blind Period [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.

  • Percentage of Patients With Any Diarrhea or Watery Rescue-free Bowel Movements (RFBM) During Open-label Period. [ Time Frame: weeks 5-12 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.

  • Change in Percentage of Rescue-free Bowel Movements (RFBM) With a Sensation of Complete Evacuation From Baseline During Double-blind Period [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 460
Study Start Date: August 2007
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1 Other: placebo
placebo
Experimental: 2 Drug: N-methylnaltrexone bromide (MOA-728)
Subcutaneous
Experimental: 3 Drug: N-methylnaltrexone bromide (MOA-728)
Subcutaneous

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00529087

  Show 78 Study Locations
Sponsors and Collaborators
Salix Pharmaceuticals
Progenics Pharmaceuticals, Inc.
Investigators
Study Director: Jeff Cohn Salix Pharmaceuticals
  More Information

No publications provided by Salix Pharmaceuticals

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Salix Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00529087     History of Changes
Other Study ID Numbers: 3200K1-3356
Study First Received: September 11, 2007
Results First Received: December 24, 2009
Last Updated: September 7, 2011
Health Authority: Canada: Health Canada
United States: Food and Drug Administration

Keywords provided by Salix Pharmaceuticals:
Opioid-Induced Constipation

Additional relevant MeSH terms:
Constipation
Signs and Symptoms, Digestive
Signs and Symptoms
Methylnaltrexone
Naltrexone
Analgesics, Opioid
Narcotic Antagonists
Physiological Effects of Drugs
 Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Analgesics
Central Nervous System Depressants

ClinicalTrials.gov processed this record on May 22, 2013