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

Constipation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00529087
• Other study ID #: 3200K1-3356
• Status: Completed
• Phase: Phase 3
• Start date: August 2007
• Est. completion date: December 2008

Study information

• Verified date: November 2019
• Source: Bausch Health Americas, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 460
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Constipation

Intervention

Drug:
• N-methylnaltrexone bromide (MOA-728)
Subcutaneous

Other:
• placebo
placebo

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Bausch Health Americas, Inc.	Progenics Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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