Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Methylnaltrexone · 20 trials · 17 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 evaluate plasma pharmacokinetics of multiple-doses of intravenous methylnaltrexone in healthy human volunteers.
To assess the potential effects of cimetidine on the pharmacokinetics of MNTX
Evaluate the PK of MNTX in healthy adult and healthy elderly male and female human subjects following MNTX administration as a single IV dose, and at steady state during multiple IV doses
The objective of this study is to assess the effect of SC or IV doses of MNTX on CYP450 2D6 activity.
To study the pharmacokinetics of MNTX following a single IV dose of 14C-MNTX in normal, healthy volunteers.
The primary objective of the study is to compare the effects of clinical and supratherapeutic doses of MNTX with the effects of placebo on QTcI duration in healthy volunteers.
To evaluate the pharmacokinetics of MNTX administered subcutaneously as a single dose in individuals with impaired liver and hepatic function compared to healthy controls.
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 determine PK, dose proportionality, and urinary excretion of single, oral doses of MNTX in normal healthy volunteers
To investigate the potential benefit of methylnaltrexone in preventing or treating opioid-induced urinary retention.
The objective of this study is to determine the plasma pharmacokinetic of single, ascending, subcutaneous doses and a single intravenous dose of methylnaltrexone (MNTX) in normal healthy male subjects.
| 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. |
| 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 | - |
| Arm 4 | PLACEBO_COMPARATOR | - |
| Arm1 | EXPERIMENTAL | MNTX active treatment |
| Arm 5 | ACTIVE_COMPARATOR | - |
| 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. |
| Methylnaltrexone (MOA-728) | DRUG | - |
| SC Methylnaltrexone | DRUG | - |
| SC Placebo | DRUG | - |
| SC Methylnaltrexone (MNTX) | DRUG | - |
| IV Methylnaltrexone (MNTX) | DRUG | - |
| IV Methylnaltrexone | DRUG | - |
| Oral Paroxetine | DRUG | - |
| Methylnaltrexone (MNTX) | DRUG | Dose 1 |
| Moxifloxacin | DRUG | - |
| Oral methylnaltrexone | DRUG | - |
| Oral placebo | DRUG | - |
| Naloxone | 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)...
Methylnaltrexone is an investigational small molecule being studied for opioid-induced constipation, post-operative ileus, and constipation in various patient populations, including advanced illness patients. It is also being evaluated in healthy volunteers for research purposes. The drug is in clinical development and has not been confirmed as approved by the FDA.
Methylnaltrexone is a small molecule that targets opioid receptors in the gastrointestinal tract. By acting on these receptors, it is designed to counteract the constipating effects of opioid medications without affecting their pain-relieving properties. This mechanism is being investigated in clinical trials for conditions like opioid-induced constipation.
Methylnaltrexone is being developed by Bausch Health Companies Inc., a company publicly traded under the ticker symbol BHC. The drug is currently in Phase 3 clinical development for gastrointestinal conditions, with ongoing research conducted by this developer.
Methylnaltrexone is in Phase 3 clinical development. It has completed two Phase 3 trials, including a study in advanced illness patients with opioid-induced constipation and an open-label treatment extension. The drug remains investigational and is not yet approved for commercial use.
Methylnaltrexone has been studied in several completed clinical trials. NCT00401362 was a Phase 3 single-dose efficacy study in advanced illness patients with opioid-induced constipation. NCT01367548 was a Phase 2 trial for post-operative ileus prevention. NCT01367561 was a Phase 1 study in healthy males, and NCT01367600 was a Phase 3 open-label extension.
Methylnaltrexone is also known by the brand name Relistor. It is a peripherally acting mu-opioid receptor antagonist used to treat opioid-induced constipation. The drug is being developed by Bausch Health Companies Inc. and is currently in Phase 3 clinical trials for various gastrointestinal indications.