Trial Outcomes & Findings for Study of Subcutaneous Methylnaltrexone (MNTX) in the Treatment of Opioid-Induced Constipation During Rehabilitation After Orthopedic Procedures (NCT NCT00640146)

Last Updated: 2019-09-04

Results Overview

Percentage of participants who had a laxation (that is, bowel movement) within 2 hours after the first dose of study drug, were reported. Participants taking stool softeners within 24 hours of study drug dosing and participants taking rescue laxative medications within 48 hours of study drug dosing were assessed as treatment failures.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

37 participants

Primary outcome timeframe

2 hours

Results posted on

2019-09-04

Participant Flow

A total of 37 participants were randomized in 1:1 ratio to receive either methylnaltrexone (MNTX) or placebo. Originally, participants were receiving treatment for up to 7 days. Then, after Protocol Amendment 1 (12 March 2008), the duration of treatment was changed from "up to 7 days" to "up to 4 days".

Participant milestones

Participant milestones
Measure	MNTX Participants received methylnaltrexone (MNTX) 12 milligrams (mg) subcutaneously (SC) once daily for up to 4 or 7 days, depending upon the protocol version under which each participant was enrolled.	Placebo Participants received placebo matched to MNTX SC once daily for up to 4 or 7 days, depending upon the protocol version under which each participant was enrolled.
Overall Study STARTED	19	18
Overall Study Received at Least 1 Dose of Study Drug	18	15
Overall Study COMPLETED	15	12
Overall Study NOT COMPLETED	4	6

Reasons for withdrawal

Reasons for withdrawal
Measure	MNTX Participants received methylnaltrexone (MNTX) 12 milligrams (mg) subcutaneously (SC) once daily for up to 4 or 7 days, depending upon the protocol version under which each participant was enrolled.	Placebo Participants received placebo matched to MNTX SC once daily for up to 4 or 7 days, depending upon the protocol version under which each participant was enrolled.
Overall Study Adverse Event	2	0
Overall Study Lost to Follow-up	0	1
Overall Study Lack of Efficacy	0	1
Overall Study Withdrawal by Subject	1	1
Overall Study Randomized but not treated	1	3

Baseline Characteristics

Study of Subcutaneous Methylnaltrexone (MNTX) in the Treatment of Opioid-Induced Constipation During Rehabilitation After Orthopedic Procedures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MNTX n=18 Participants Participants received MNTX 12 mg SC once daily for up to 4 or 7 days, depending upon the protocol version under which each participant was enrolled.	Placebo n=15 Participants Participants received placebo matched to MNTX SC once daily for up to 4 or 7 days, depending upon the protocol version under which each participant was enrolled.	Total n=33 Participants Total of all reporting groups
Age, Continuous	64.2 years STANDARD_DEVIATION 9.04 • n=5 Participants	65.2 years STANDARD_DEVIATION 11.56 • n=7 Participants	64.7 years STANDARD_DEVIATION 10.11 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 hours

Population: MITT population included all randomized participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	MNTX n=18 Participants Participants received MNTX 12 mg SC once daily for up to 4 or 7 days, depending upon the protocol version under which each participant was enrolled.	Placebo n=15 Participants Participants received placebo matched to MNTX SC once daily for up to 4 or 7 days, depending upon the protocol version under which each participant was enrolled.
Percentage of Participants With Laxation Response Within 2 Hours of the First Dose	33.33 percentage of participants Interval 13.34 to 59.01	0 percentage of participants Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: 4 hours

Population: MITT population included all randomized participants who received at least 1 dose of study drug.

Percentage of participants who had a laxation (that is, bowel movement) within 4 hours after the first dose of study drug, were reported. Participants taking stool softeners within 24 hours of study drug dosing and participants taking rescue laxative medications within 48 hours of study drug dosing were assessed as treatment failures.

Outcome measures

Outcome measures
Measure	MNTX n=18 Participants Participants received MNTX 12 mg SC once daily for up to 4 or 7 days, depending upon the protocol version under which each participant was enrolled.	Placebo n=15 Participants Participants received placebo matched to MNTX SC once daily for up to 4 or 7 days, depending upon the protocol version under which each participant was enrolled.
Percentage of Participants With Laxation Response Within 4 Hours of the First Dose	38.89 percentage of participants Interval 17.3 to 64.25	6.67 percentage of participants Interval 0.17 to 31.95

SECONDARY outcome

Timeframe: Baseline (Day 1) up to Day 4 or 7

Population: MITT population included all randomized participants who received at least 1 dose of study drug. One participant with bowel movement prior to dosing was excluded from placebo arm.

A rescue-free laxation was defined as a laxation without use of any rescue medication or rescue procedures. Time to first rescue-free bowel movement following the first dose of study drug was reported.

Outcome measures

Outcome measures
Measure	MNTX n=18 Participants Participants received MNTX 12 mg SC once daily for up to 4 or 7 days, depending upon the protocol version under which each participant was enrolled.	Placebo n=14 Participants Participants received placebo matched to MNTX SC once daily for up to 4 or 7 days, depending upon the protocol version under which each participant was enrolled.
Time to First Rescue-Free Bowel Movement (Laxation)	23.8 hours Standard Error 6.30	46.7 hours Standard Error 6.49

Adverse Events

MNTX

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Director of Clinical Operations

Bausch Health Americas, Inc

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Please contact Sponsor directly for additional information.
Publication restrictions are in place

Restriction type: OTHER

Measure	MNTX n=18 participants at risk Participants received MNTX 12 mg SC once daily for up to 4 or 7 days, depending upon the protocol version under which each participant was enrolled.	Placebo n=15 participants at risk Participants received placebo matched to MNTX SC once daily for up to 4 or 7 days, depending upon the protocol version under which each participant was enrolled.
Blood and lymphatic system disorders Anaemia	5.6% 1/18 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/15 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/18 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.	6.7% 1/15 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal distension	5.6% 1/18 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/15 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain	5.6% 1/18 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/15 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal tenderness	5.6% 1/18 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/15 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	5.6% 1/18 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/15 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	5.6% 1/18 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/15 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	5.6% 1/18 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/15 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Oedema peripheral	0.00% 0/18 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.	13.3% 2/15 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Urinary tract infection	5.6% 1/18 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/15 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Wound infection	5.6% 1/18 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/15 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Procedural pain	0.00% 0/18 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.	6.7% 1/15 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/18 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.	6.7% 1/15 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Headache	5.6% 1/18 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/15 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Somnolence	0.00% 0/18 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.	6.7% 1/15 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/18 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.	6.7% 1/15 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Hypotension	5.6% 1/18 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.	0.00% 0/15 • Baseline (Day 1) up to Day 30 Safety population included all randomized participants who received at least 1 dose of study drug.