Study Evaluating the Efficacy and Safety of Subcutaneous Methylnaltrexone (MOA-728) for the Treatment of Opioid-Induced-Constipation

Phase 3

Completed

• Conditions: Constipation
• Interventions: Drug: Placebo; Drug: Methylnaltrexone

• Registration Number: NCT00936884
• Lead Sponsor: Bausch Health Americas, Inc.

Brief Summary

The primary purpose of this study is to evaluate the safety, efficacy, and tolerability of subcutaneous (injection beneath the skin) MOA-728 versus placebo in adult Asian subjects with opioid-induced constipation associated with advanced illness (ie, a terminal illness such as incurable cancer or other end-stage disease) or chronic nonmalignant pain.

Detailed Description

Subjects received subcutaneous methylnaltrexone (also referred to as MOA-728 or MNTX) or placebo every other day beginning on Day 1 up to a maximum of 7 doses during the 2-week double-blind period.

Inclusion criteria for this study included subjects with advanced illness or subjects with chronic nonmalignant pain. The actual study population included only subjects with cancer-related advanced illness.

All subjects who completed the double-blind treatment phase of this study could elect to receive methylnaltrexone during a 12-week open-label extension study, provided eligibility criteria were met. Subjects who did not continue in the open-label extension study had a follow-up visit 2 weeks after their last dose of test article.

Study Timeline

• Study Start: 2009-07
• Study First Submitted: 2009-07-08
• Study First Submitted QC: 2009-07-09
• Study First Posted: 2009-07-10
• Primary Completion: 2013-11
• Study Completion: 2013-11
• Results First Submitted: 2019-11-26
• Status Verified: 2019-12
• Results First Submitted QC: 2019-12-13
• Last Update Submitted: 2019-12-13
• Results First Posted: 2020-01-02
• Last Update Posted: 2020-01-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Men and women who are at least 18 years of age, and who have a diagnosis of advanced illness with anticipated life expectancy >= 1 month;
• Is receiving a regular dose of opioids for the control of pain;
• Has a diagnosis of opioid induced constipation;
• Is on a stable laxative regimen.

Exclusion Criteria

• Has a known or suspected mechanical gastrointestinal obstruction, or any potential non-opioid cause of bowel dysfunction contributed to constipation;
• Has evidence of current fecal impaction;
• Has evidence of active diverticulitis, or peritonitis, or a history of bowel surgery within 30 days before test article administration;
• Has a body weight less than 27 kg
• Has any major illness/condition that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in and completion of the study, or could preclude the evaluation of the subject's response.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo once every other day.
Methylnaltrexone open-label	Methylnaltrexone	Subjects who completed the double-blind period had the option to receive methylnaltrexone once every other day during a 12-week, open-label extension period.
Methylnaltrexone double-blind	Methylnaltrexone	Methylnaltrexone once every other day.

Primary Outcome Measures

Name	Time	Method
The Proportion of Subjects Having a Rescue-free Bowel Movement (RFBM) Within 4 Hours After the First Injection.	Up to 4 hours after the first injection	There were 2 co-primary endpoints for this study. This measurement is the first of the 2 co-primary endpoints. This endpoint measures the percentage of patients who had an RFBM within 4 hours after the first dose of test article during the double-blind period; data are expressed as percentages of patients for the MNTX and placebo groups. To qualify as rescue free, the bowel movement could not occur within 6 hours after a rectal intervention (ie, rectal suppository, enema, manual disimpaction). Note that efficacy results (primary and secondary outcomes) are presented for the double-blind period only. Therefore, no efficacy results are presented for the open-label period.
The Proportion of Subjects Having a Rescue-free Bowel Movement (RFBM) Within 4 Hours After Each Dose During Double-blind Period.	Within 4 Hours After Each Dose During the 2 weeks Double-Blind Period	This measurement is the second of the 2 co-primary endpoints. This endpoint measures the percentage of patients who had an RFBM within 4 hours after each dose of test article during the double-blind period; data are expressed as percentages of patients by dose (first, second, third, fourth, etc.) for the MNTX and placebo groups. The definition of RFBM is described above (see first co-primary endpoint).

Secondary Outcome Measures

Name	Time	Method
Percentage of Injections Resulting in RFBM Within 4 Hours After Test Article Administration.	Within 4 Hours After Each Dose During the 2 weeks Double-Blind Period	This endpoint measures the percentage of injections resulting in RFBMs within 4 hours after test article administration during the double-blind period. The percentage of injections resulting in RFBMs is calculated for each patient and then data are expressed as the mean (± standard deviation) percentage for the MNTX and placebo groups. The definition of RFBM is described above (see first co-primary endpoint).