Opioid-Induced Constipation
Conditions
Keywords
opioid-induced constipation
Brief summary
This study will evaluate the safety and efficacy of methylnaltrexone administered as subcutaneous injections in subjects who have opioid-induced constipation and an advanced illness. The hypothesis is that methylnaltrexone will be safe and effective in relieving opioid-induced constipation in these subjects.
Interventions
DRUGMethylnaltrexone
DRUGPlacebo
Sponsors
Progenics Pharmaceuticals, Inc.
Bausch Health Americas, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Is an adult 18 years of age or older * Has a diagnosis of advanced illness (ie, a terminal illness such as incurable cancer or other end-stage disease) * Has a life expectancy of at least 1 month. * Is receiving opioids on a regular schedule (not just as-needed or rescue doses) for the control of pain or discomfort for at least 2 weeks before the first dose of study drug. * Has constipation that is caused by opioid medications.
Exclusion criteria
* Has a known or suspected allergy to methylnaltrexone or other similar compounds (e.g. naltrexone or naloxone). * Has a known or suspected mechanical gastrointestinal obstruction. * Has any potential nonopioid cause of bowel dysfunction that might be a major contributor to the constipation. * Has any other clinically important abnormalities as determined by the investigator that may interfere with his or her participation in or compliance with the study. * Receiving opioid antagonist or partial antagonist products.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Subjects Who Have a Rescue-free Laxation Response Within 4 Hours After at Least 2 of the First 4 Doses | 7 days | This outcome measures the proportion of subjects who had a rescue-free laxation (ie, bowel movement) within 4 hours after at least 2 of the first 4 doses of study drug. A rescue free laxation was defined as a laxation without use of any rescue medication or rescue procedures within 4 hours prior to the laxation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Rescue-free Laxation (Following the First Dose of Study Drug). | 14 days | This outcome measures the time from first dose of study drug to the first rescue-free laxation (ie, bowel movement). A rescue free laxation was defined as a laxation without use of any rescue medication or rescue procedures within 4 hours prior to the laxation. |
Countries
Australia, Belgium, Brazil, Canada, France, Germany, Italy, Mexico, Spain, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Methylnaltrexone Bromide Methylnaltrexone bromide: Methylnaltrexone subcutaneously every other day for 14 days (ie, 7 doses). | 116 |
| Placebo Placebo: Placebo subcutaneously every other day for 14 days (ie, 7 doses). | 114 |
| Total | 230 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 7 |
| Overall Study | Death | 7 | 11 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | no study drug for low GFR, health cond. | 1 | 3 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | Methylnaltrexone Bromide | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 56 Participants | 57 Participants | 113 Participants |
| Age, Categorical Between 18 and 65 years | 60 Participants | 57 Participants | 117 Participants |
| Age, Continuous | 65.31 years STANDARD_DEVIATION 12.92 | 65.67 years STANDARD_DEVIATION 12.97 | 65.49 years STANDARD_DEVIATION 12.92 |
| Glomerular filtration rate < 30 mL/min/1.73 m^2 | 3 participants | 3 participants | 6 participants |
| Glomerular filtration rate ≥ 30 mL/min/1.73 m^2 | 110 participants | 108 participants | 218 participants |
| Glomerular filtration rate Missing | 3 participants | 3 participants | 6 participants |
| Sex: Female, Male Female | 56 Participants | 58 Participants | 114 Participants |
| Sex: Female, Male Male | 60 Participants | 56 Participants | 116 Participants |
| Underlying Advanced Illness Cancer | 79 participants | 73 participants | 152 participants |
| Underlying Advanced Illness Cardiovascular disease | 13 participants | 11 participants | 24 participants |
| Underlying Advanced Illness Neurologic disease | 4 participants | 3 participants | 7 participants |
| Underlying Advanced Illness Other | 6 participants | 14 participants | 20 participants |
| Underlying Advanced Illness Pulmonary disease (other than malignancy) | 14 participants | 13 participants | 27 participants |
| Weight < 62 kg | 45 participants | 41 participants | 86 participants |
| Weight ≥ 62 kg | 71 participants | 73 participants | 144 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 66 / 116 | 52 / 114 |
| serious Total, serious adverse events | 14 / 116 | 24 / 114 |
Outcome results
Primary
The Proportion of Subjects Who Have a Rescue-free Laxation Response Within 4 Hours After at Least 2 of the First 4 Doses
This outcome measures the proportion of subjects who had a rescue-free laxation (ie, bowel movement) within 4 hours after at least 2 of the first 4 doses of study drug. A rescue free laxation was defined as a laxation without use of any rescue medication or rescue procedures within 4 hours prior to the laxation.
Time frame: 7 days
Population: The analysis population included subjects who received ≥ 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methylnaltrexone Bromide | The Proportion of Subjects Who Have a Rescue-free Laxation Response Within 4 Hours After at Least 2 of the First 4 Doses | 62.9 percentage of participants |
| Placebo | The Proportion of Subjects Who Have a Rescue-free Laxation Response Within 4 Hours After at Least 2 of the First 4 Doses | 9.6 percentage of participants |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Time to First Rescue-free Laxation (Following the First Dose of Study Drug).
This outcome measures the time from first dose of study drug to the first rescue-free laxation (ie, bowel movement). A rescue free laxation was defined as a laxation without use of any rescue medication or rescue procedures within 4 hours prior to the laxation.
Time frame: 14 days
Population: The analysis population included subjects who received ≥ 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Methylnaltrexone Bromide | Time to First Rescue-free Laxation (Following the First Dose of Study Drug). | 0.79 hours |
| Placebo | Time to First Rescue-free Laxation (Following the First Dose of Study Drug). | 23.58 hours |
p-value: <0.0001Log Rank