Opioid-Induced Constipation
Conditions
Keywords
Opioid-Induced Constipation
Brief summary
This is an open-label, multicenter extension of study 3200K1-4000-WW that will evaluate the safety of methylnaltrexone. This drug will be administered by subcutaneous injection and will be tested in late stage, advanced illness patients who have constipation caused by opioid pain relievers. This study will last 3 months.
Interventions
Sponsors
Progenics Pharmaceuticals, Inc.
Bausch Health Americas, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has completed study 3200K1-4000-WW, including 2 weeks of therapy and completion of all post baseline efficacy, safety, and health outcomes assessments. * Is receiving opioids on a regular schedule, not just as needed to control pain. * Likely to continue to need treatment of OIC for the duration of participation in the study.
Exclusion criteria
* Has a suspected mechanical gastrointestinal obstruction, fecal impaction, or clinically important active diverticular disease as determined by the investigator. * Currently using an opioid antagonist or partial antagonist. * Has any other clinically important abnormalities such that risk to patient of participation outweighs the potential benefit of therapy as determined by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Laxations Per Subject Within 24 Hours of Dosing Per Week. | 10 weeks | This was defined as the total number of days with a laxation (ie, a bowel movement) within 24 hours after dosing in each 7-day interval after the start of dosing. Results shown are the ranges (lowest and highest weekly values) of mean (± standard deviation) numbers of laxations within 24 hours of dosing per week during the 10-week treatment period for each group. |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Mexico, Portugal, United Kingdom, United States
Participant flow
Recruitment details
Patients participated in this study at sites in Australia, Belgium, Brazil, Canada, France, Germany, Italy, Mexico, Spain, Sweden, the United Kingdom, and the United States.
Pre-assignment details
The main eligibility criteria for this study were completion of 2 weeks of therapy and all post-baseline efficacy, safety, and health outcomes assessments in lead-in study MNTX4000 and an anticipated continued need for treatment of opioid-induced constipation.
Participants by arm
| Arm | Count |
|---|---|
| Methylnaltrexone Bromide 8 mg Methylnaltrexone subcutaneously as needed no more than 1 dose in a 24-hour period for a maximum of 10 weeks in this study.
Subjects received 0.4 mL (8 mg) every other day if weight between 38 and \<62 kg. Subjects with impaired kidney function received reduced doses according to instructions in the Relistor prescribing information. | 57 |
| Methylnaltrexone Bromide 12 mg Methylnaltrexone subcutaneously as needed no more than 1 dose in a 24-hour period for a maximum of 10 weeks in this study.
Subjects received 0.6 mL (12 mg) every other day if weight ≥ 62kg. Subjects with impaired kidney function received reduced doses according to instructions in the Relistor prescribing information. | 92 |
| Total | 149 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 7 |
| Overall Study | Death | 14 | 23 |
| Overall Study | hospice discharge, caregiver requests | 3 | 2 |
| Overall Study | Lack of Efficacy | 4 | 1 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 11 |
Baseline characteristics
| Characteristic | Methylnaltrexone Bromide 8 mg | Methylnaltrexone Bromide 12 mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 33 Participants | 46 Participants | 79 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 46 Participants | 70 Participants |
| Age, Continuous | 68.07 years STANDARD_DEVIATION 14.29 | 64.59 years STANDARD_DEVIATION 11.98 | 65.92 years STANDARD_DEVIATION 12.98 |
| Glomerular filtration rate < 30 mL/min/1.73 m^2 | 2 participants | 0 participants | 2 participants |
| Glomerular filtration rate ≥ 30 mL/min/1.73 m^2 | 54 participants | 89 participants | 143 participants |
| Glomerular filtration rate Missing | 1 participants | 3 participants | 4 participants |
| Sex: Female, Male Female | 44 Participants | 33 Participants | 77 Participants |
| Sex: Female, Male Male | 13 Participants | 59 Participants | 72 Participants |
| Underlying Advanced Illness Cancer | 36 Participants | 49 Participants | 85 Participants |
| Underlying Advanced Illness Cardiovascular disease | 4 Participants | 15 Participants | 19 Participants |
| Underlying Advanced Illness Neurologic disease | 3 Participants | 3 Participants | 6 Participants |
| Underlying Advanced Illness Other | 7 Participants | 7 Participants | 14 Participants |
| Underlying Advanced Illness Pulmonary disease | 7 Participants | 18 Participants | 25 Participants |
| Weight 38 to < 62 kg | 54 participants | 0 participants | 54 participants |
| Weight ≥ 62 kg | 3 participants | 92 participants | 95 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 45 / 57 | 60 / 92 |
| serious Total, serious adverse events | 22 / 57 | 37 / 92 |
Outcome results
Primary
Number of Laxations Per Subject Within 24 Hours of Dosing Per Week.
This was defined as the total number of days with a laxation (ie, a bowel movement) within 24 hours after dosing in each 7-day interval after the start of dosing. Results shown are the ranges (lowest and highest weekly values) of mean (± standard deviation) numbers of laxations within 24 hours of dosing per week during the 10-week treatment period for each group.
Time frame: 10 weeks
Population: The analysis population included subjects who received study drug and had laxation data and drug administration data. Two subjects in the 12 mg/day group had no drug administration data and were not included in efficacy analyses (but they were included in baseline characteristics and safety analyses).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methylnaltrexone Bromide 8 mg | Number of Laxations Per Subject Within 24 Hours of Dosing Per Week. | Lowest weekly average # laxations/week | 1.7 Number of laxations | Standard Deviation 1.5 |
| Methylnaltrexone Bromide 8 mg | Number of Laxations Per Subject Within 24 Hours of Dosing Per Week. | Highest weekly average # laxations/week | 2.6 Number of laxations | Standard Deviation 2.4 |
| Methylnaltrexone Bromide 12 mg | Number of Laxations Per Subject Within 24 Hours of Dosing Per Week. | Lowest weekly average # laxations/week | 2.4 Number of laxations | Standard Deviation 2.3 |
| Methylnaltrexone Bromide 12 mg | Number of Laxations Per Subject Within 24 Hours of Dosing Per Week. | Highest weekly average # laxations/week | 3.4 Number of laxations | Standard Deviation 3.4 |