Constipation
Conditions
Keywords
treatment for opioid-induced constipation
Brief summary
This study is designed to evaluate the long-term safety and tolerability of the subcutaneous (SC) injection form of N-methylnaltrexone bromide (MOA-728) for the treatment of opioid-induced constipation in participants with nonmalignant pain. The study consists of a 2-week screening period, a 48-week open-label treatment period and a 2 week follow-up period. Participants will need to agree to self-administer SC injections, complete daily diaries, and check-in via a daily telephone call during the study.
Interventions
MOA-728 will be administered as per the dose and schedule specified in the arm.
Sponsors
Pfizer
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
* Men and women 18 years or older. * A history of pain of at least 2 months duration before the screening visit due to documented underlying nonmalignant condition. * A history of constipation due to opioid use during 1 month before the screening visit.
Exclusion criteria
* A diagnosis of significant gastrointestinal (GI) disorder such as bowel obstruction, fecal incontinence or rectal prolapse. * A history of active inflammatory bowel disease, irritable bowel syndrome, or megacolon within 6 months before the screening visit. * A history of malignancy, other than basal cell or squamous cell skin carcinoma, within 5 years before the screening visit. * A history of chronic constipation before initiation of opioid therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Baseline up to Week 50 | Adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Serious adverse events (SAEs) included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as an AE that emerged during the treatment period. Any TEAEs included both treatment-emergent SAEs and non-serious AEs. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weekly Bowel Movement (BM) Rate Through Follow-up | Baseline, follow-up (14 days [Week 49 to 50]) | Weekly BM rate was derived as the total number of BMs reported in a month divided by the total number of days with non-missing BM diary information in the same month, then multiplied by 7 to normalize to a weekly rate. If the total number of days with non-missing BM diary information in a given month was less than 10 days, the weekly BM rate for the month was defined as missing. The weekly BM rate at baseline was calculated based on the screening period (Days -14 to -1). If the total number of days with non-missing BM diary information during the screening period was less than 5 days, the weekly BM rate at baseline was defined as missing. |
Countries
Australia, Canada, Colombia, South Korea, Spain, United States
Participant flow
Pre-assignment details
A total of 1040 participants who met the inclusion/exclusion criteria were assigned to receive treatment and 1034 of these participants received at least 1 dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| MOA-728 12 mg QD Participants received MOA-728 12 mg SC QD for 48 weeks. Dosing could be adjusted to PRN basis with a minimum 1 dose per week and maximum 1 dose per day. | 1,034 |
| Total | 1,034 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 157 |
| Overall Study | Death | 4 |
| Overall Study | Enrolled but not treated | 6 |
| Overall Study | Failed to return | 96 |
| Overall Study | Investigator request | 8 |
| Overall Study | Lack of Efficacy | 46 |
| Overall Study | Other than specified | 30 |
| Overall Study | Protocol Violation | 85 |
| Overall Study | Withdrawal by Subject | 131 |
Baseline characteristics
| Characteristic | MOA-728 12 mg QD |
|---|---|
| Age, Continuous | 51.67 years STANDARD_DEVIATION 10.84 |
| Sex: Female, Male Female | 669 Participants |
| Sex: Female, Male Male | 365 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 564 / 1,034 |
| serious Total, serious adverse events | 104 / 1,034 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Serious adverse events (SAEs) included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as an AE that emerged during the treatment period. Any TEAEs included both treatment-emergent SAEs and non-serious AEs. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline up to Week 50
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MOA-728 12 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 817 Participants |
| MOA-728 12 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | SAEs | 104 Participants |
Secondary
Change From Baseline in Weekly Bowel Movement (BM) Rate Through Follow-up
Weekly BM rate was derived as the total number of BMs reported in a month divided by the total number of days with non-missing BM diary information in the same month, then multiplied by 7 to normalize to a weekly rate. If the total number of days with non-missing BM diary information in a given month was less than 10 days, the weekly BM rate for the month was defined as missing. The weekly BM rate at baseline was calculated based on the screening period (Days -14 to -1). If the total number of days with non-missing BM diary information during the screening period was less than 5 days, the weekly BM rate at baseline was defined as missing.
Time frame: Baseline, follow-up (14 days [Week 49 to 50])
Population: All participants who received at least one dose of study drug. Here, 'Number analyzed' signifies participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MOA-728 12 mg QD | Change From Baseline in Weekly Bowel Movement (BM) Rate Through Follow-up | Baseline | 3.9 BM/week | Standard Deviation 2.8 |
| MOA-728 12 mg QD | Change From Baseline in Weekly Bowel Movement (BM) Rate Through Follow-up | Change during follow-up | 0.5 BM/week | Standard Deviation 2.7 |