Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication • RELISTOR is an opioid antagonist. RELISTOR tablets and RELISTOR injection are indicated for the treatment of opioid-induced constipation (OIC) in adults with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation.
Also known as Methylnaltrexone, Relistor, MNTX
MOA-728 · 20 trials · 16 indications
RFBM was defined as a bowel movement without laxative use within 24 hours prior to bowel movement.
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.
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).
Time to first bowel movement was measured from the end of surgery (defined as the time when the last skin suture or staple was placed in the participant). Time of the first bowel movement was recorded on the electronic case report form (eCRF). The first bowel movement was defined as a normal stool for a postoperative participant based on the clinical judgment of the investigator or designee. Analysis was performed by Kaplan-Meier estimate. Participants who had a bowel movement but were readmitted to the hospital within 1 week after discharge with a diagnosis of postoperative ileus (POI) were considered censored at the time of the first bowel movement as if the bowel movement had not occurred.
To provide access to treatment with MNTX, administered SC, to patients who completed Progenics' Protocol MNTX 302
To determine the efficacy of a single dose of SC MNTX compared with placebo in inducing laxation within 4 hours. To determine the efficacy of SC MNTX every other day over a 1-week treatment period in relieving OIC in patients with AMI.
The primary objective is to determine the efficacy of SC MNTX administered as a single dose, dose 1 and dose 2 compared with placebo in inducing laxation in 4 hours in patients with advanced medical illness and OIC who are poorly responsive to laxatives.
To assess the activity of parenterally administered MNTX compared with placebo in shortening the duration of or preventing post-operative ileus in patients who have undergone segmental colectomies.
To access the efficacy of various fixed unit doses of MNTX SC in patients with advanced medical illnesses and poorly controlled opioid-induced constipation.
To compare the PK of MNTX administered subcutaneously as a single dose in patients with impaired renal function with the PK of MNTX administered to healthy subjects.
To evaluate the pharmacokinetics of MNTX administered subcutaneously as a single dose in individuals with impaired liver and hepatic function compared to healthy controls.
| Arm | Type | Description |
|---|---|---|
| MNTX 150 mg | EXPERIMENTAL | Participants will receive methylnaltrexone (MNTX) 150 milligrams (mg) (1 tablet of MNTX 150 mg and 2 matching placebo tablets) orally once daily (QD) for 28 days (4 weeks), then MNTX tablets at a dose as needed (PRN) for remaining 56 days (8 weeks). |
| MNTX 300 mg | EXPERIMENTAL | Participants will receive MNTX 300 mg (2 tablets of MNTX 150 mg each and 1 matching placebo tablet) orally QD for 28 days (4 weeks), then MNTX tablets at a dose PRN for remaining 56 days (8 weeks). |
| MNTX 450 mg | EXPERIMENTAL | Participants will receive MNTX 450 mg (3 tablets of MNTX 150 mg each) orally QD for 28 days (4 weeks), then MNTX tablets at a dose PRN for remaining 56 days (8 weeks). |
| Placebo | PLACEBO_COMPARATOR | Participants will receive 3 tablets of placebo matched to MNTX orally QD for 84 days (12 weeks). |
| Methylnaltrexone double-blind | EXPERIMENTAL | Methylnaltrexone once every other day. |
| Methylnaltrexone open-label | OTHER | 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. |
| MOA-728 12 mg | EXPERIMENTAL | Participants will receive methylnaltrexone (MOA-728) 12 mg as an IV infusion over approximately 20 minutes for approximately every 6 hours for a total of 4 doses in 24-hour period. The first dose of study drug will be administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple is placed in the participant). Dose administration will be continued for a maximum of 10 days. |
| MOA-728 24 mg | EXPERIMENTAL | Participants will receive MOA-728 24 mg as an IV infusion over approximately 20 minutes for approximately every 6 hours for a total of 4 doses in 24-hour period. The first dose of study drug will be administered within approximately 90 minutes after completion of the surgical procedure (defined as the time when the last skin suture or staple is placed in the participant). Dose administration will be continued for a maximum of 10 days. |
| MNTX 12 mg | EXPERIMENTAL | Participants will receive methylnaltrexone (MNTX) 12 milligrams (mg) as an intravenous (IV) infusion over approximately 20 minutes for every 6 hours until one of the following occurs: 1) 24 hours elapsed after the first bowel movement and the participant was tolerating clear liquids, 2) the participant was discharged from the hospital, or 3) a maximum of 10 days elapsed. The first dose of study drug will be administered within the first 90 minutes after the end of surgery (defined as the time when the last skin suture or staple is placed in the participant). |
| MNTX 24 mg | EXPERIMENTAL | Participants will receive MNTX 24 mg as an IV infusion over approximately 20 minutes for every 6 hours until one of the following occurs: 1) 24 hours elapsed after the first bowel movement and the participant was tolerating clear liquids, 2) the participant was discharged from the hospital, or 3) a maximum of 10 days elapsed. The first dose of study drug will be administered within the first 90 minutes after the end of surgery (defined as the time when the last skin suture or staple is placed in the participant). |
| Arm 1 | EXPERIMENTAL | - |
| Arm 2 | PLACEBO_COMPARATOR | - |
| Arm 3 | PLACEBO_COMPARATOR | - |
| 150 mg | EXPERIMENTAL | MOA-728 |
| 300 mg | EXPERIMENTAL | MOA-728 |
| 450 mg | EXPERIMENTAL | MOA-728 |
| 600 mg | EXPERIMENTAL | MOA-728 |
| Name | Type | Description |
|---|---|---|
| Methylnaltrexone | DRUG | Methylnaltrexone will be administered as per the dose and schedule specified in the respective arms. |
| Placebo | DRUG | Placebo matching to methylnaltrexone will be administered as per the schedule specified in the respective arms. |
| MOA-728 | DRUG | MOA-728 will be administered per the dose and schedule specified in the arm. |
| Methylnaltrexone (MOA-728) | DRUG | - |
| SC Methylnaltrexone | DRUG | - |
| SC Placebo | DRUG | - |
| SC Methylnaltrexone (MNTX) | DRUG | - |
| IV Methylnaltrexone (MNTX) | DRUG | - |
| SC MNTX | DRUG | Dose 1 |
| Methylnaltrexone (MNTX) | DRUG | - |
Key Inclusion Criteria: 1. History of chronic non-malignant pain (originating from a non-malignant source) with condition(s) underlying the chronic pain of greater than or equal to (≥) 2 months' duration before the screening visit. 2. Taking oral, transdermal, intravenous (IV), or subcutaneous (SC)...
MOA-728 is an investigational small molecule developed by Bausch Health Companies Inc. (ticker BHC). It has been studied in adults for constipation, ileus, postoperative complications, and in methadone-maintenance subjects. It is not approved and remains in clinical development, with Phase 1 listed as its current stage.
MOA-728 has been studied for constipation, including opioid-induced bowel dysfunction in adults with chronic non-malignant pain, for postoperative ileus after ventral hernia repair, and in subjects on stable methadone maintenance. These are investigational uses; the drug is not approved for any indication.
MOA-728 is developed by Bausch Health Companies Inc., which trades under the ticker BHC. The company sponsored the clinical studies of MOA-728 in constipation, ileus, and methadone-maintenance subjects.
MOA-728 is in Phase 1 development and is investigational. Its completed studies include Phase 1, Phase 2, and Phase 3 trials, but the current listed stage is Phase 1. It is not FDA approved for any indication.
Three completed trials are registered for MOA-728: NCT00605644, an oral study in opioid-induced bowel dysfunction in chronic non-malignant pain; NCT00528970, an intravenous study in postoperative ileus after ventral hernia repair; and NCT00447811 in subjects on stable methadone maintenance. A fourth completed study, NCT00444158, compared 20-minute and 4-hour intravenous infusions in stable methadone subjects.
Across the registered MOA-728 studies, total enrollment is 572 participants. Individual trials enrolled 128 participants in the oral constipation study, 374 in the postoperative ileus study, and 24 in the infusion-comparison study in stable methadone subjects. The trials were randomized and double blind.