Trial Outcomes & Findings for A Study of Oral Methylnaltrexone (MNTX) for the Treatment of Opioid-Induced Constipation (OIC) in Participants With Chronic, Non-Malignant Pain (NCT NCT01186770)

NCT ID: NCT01186770

Last Updated: 2019-09-06

Results Overview

RFBM was defined as a bowel movement without laxative use within 24 hours prior to bowel movement.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

804 participants

Primary outcome timeframe

Weeks 1 to 4

Results posted on

2019-09-06

Participant Flow

A total of 804 participants met inclusion/exclusion criteria and randomized in 1:1:1:1 ratio to either MNTX 150 mg, MNTX 300 mg, MNTX 450 mg, or placebo treatment groups.

Participant milestones

Participant milestones
Measure	MNTX 150 mg Participants received 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 Participants received 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 Participants received 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 Participants received 3 tablets of placebo matched to MNTX orally QD for 84 days (12 weeks).
Overall Study STARTED	201	202	200	201
Overall Study Intent-to-treat (ITT Population)	201	201	200	201
Overall Study COMPLETED	160	156	148	143
Overall Study NOT COMPLETED	41	46	52	58

Reasons for withdrawal

Reasons for withdrawal
Measure	MNTX 150 mg Participants received 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 Participants received 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 Participants received 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 Participants received 3 tablets of placebo matched to MNTX orally QD for 84 days (12 weeks).
Overall Study Ineligibility	0	0	2	0
Overall Study Protocol Violation	7	9	12	14
Overall Study Adverse Event	2	9	7	9
Overall Study Withdrawal by Subject	15	13	11	17
Overall Study Lost to Follow-up	10	6	14	9
Overall Study Insufficient response to treatment	7	8	5	7
Overall Study Other than specified	0	1	1	2

Baseline Characteristics

A Study of Oral Methylnaltrexone (MNTX) for the Treatment of Opioid-Induced Constipation (OIC) in Participants With Chronic, Non-Malignant Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MNTX 150 mg n=201 Participants Participants received MNTX 150 mg (1 tablet of MNTX 150 mg and 2 matching placebo tablets) orally QD for 28 days (4 weeks), then MNTX tablets at a dose PRN for remaining 56 days (8 weeks).	MNTX 300 mg n=201 Participants Participants received 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 n=200 Participants Participants received 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 n=201 Participants Participants received 3 tablets of placebo matched to MNTX orally QD for 84 days (12 weeks).	Total n=803 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	185 Participants n=5 Participants	182 Participants n=7 Participants	181 Participants n=5 Participants	179 Participants n=4 Participants	727 Participants n=21 Participants
Age, Categorical >=65 years	15 Participants n=5 Participants	19 Participants n=7 Participants	19 Participants n=5 Participants	22 Participants n=4 Participants	75 Participants n=21 Participants
Age, Continuous	50.9 years STANDARD_DEVIATION 10.32 • n=5 Participants	51.5 years STANDARD_DEVIATION 10.54 • n=7 Participants	51.4 years STANDARD_DEVIATION 10.50 • n=5 Participants	52.6 years STANDARD_DEVIATION 10.33 • n=4 Participants	51.6 years STANDARD_DEVIATION 10.38 • n=21 Participants
Sex: Female, Male Female	133 Participants n=5 Participants	114 Participants n=7 Participants	128 Participants n=5 Participants	130 Participants n=4 Participants	505 Participants n=21 Participants
Sex: Female, Male Male	68 Participants n=5 Participants	87 Participants n=7 Participants	72 Participants n=5 Participants	71 Participants n=4 Participants	298 Participants n=21 Participants
Primary pain condition requiring opioid medication Back pain	132 Participants n=5 Participants	136 Participants n=7 Participants	135 Participants n=5 Participants	145 Participants n=4 Participants	548 Participants n=21 Participants
Primary pain condition requiring opioid medication Joint/extremity pain	13 Participants n=5 Participants	16 Participants n=7 Participants	11 Participants n=5 Participants	10 Participants n=4 Participants	50 Participants n=21 Participants
Primary pain condition requiring opioid medication Arthritis	20 Participants n=5 Participants	15 Participants n=7 Participants	19 Participants n=5 Participants	12 Participants n=4 Participants	66 Participants n=21 Participants
Primary pain condition requiring opioid medication Neurologic/neuropathic pain	16 Participants n=5 Participants	13 Participants n=7 Participants	16 Participants n=5 Participants	11 Participants n=4 Participants	56 Participants n=21 Participants
Primary pain condition requiring opioid medication Fibromyalgia	15 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants	12 Participants n=4 Participants	46 Participants n=21 Participants
Primary pain condition requiring opioid medication Other pain condition requiring opioids	5 Participants n=5 Participants	13 Participants n=7 Participants	8 Participants n=5 Participants	11 Participants n=4 Participants	37 Participants n=21 Participants

PRIMARY outcome

Timeframe: Weeks 1 to 4

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

RFBM was defined as a bowel movement without laxative use within 24 hours prior to bowel movement.

Outcome measures

Outcome measures
Measure	MNTX 150 mg n=201 Participants Participants received MNTX 150 mg (1 tablet of MNTX 150 mg and 2 matching placebo tablets) orally QD for 28 days (4 weeks), then MNTX tablets at a dose PRN for remaining 56 days (8 weeks).	MNTX 300 mg n=201 Participants Participants received 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 n=200 Participants Participants received 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 n=201 Participants Participants received 3 tablets of placebo matched to MNTX orally QD for 84 days (12 weeks).
Average Percentage of Dosing Days That Resulted in Rescue-Free Bowel Movements (RFBMs) Within 4 Hours of Dosing During Weeks 1 to 4	21.05 percentage of days Standard Deviation 20.116	24.64 percentage of days Standard Deviation 21.311	27.40 percentage of days Standard Deviation 23.453	18.18 percentage of days Standard Deviation 16.995

SECONDARY outcome

Timeframe: Weeks 1 to 4

Population: ITT population included all randomized participants who received at least 1 dose of study drug. Missing data was imputed using last observation carried forward (LOCF) method.

A responder was defined as at least 3 RFBMs/week, with an increase of at least 1 RFBM/week over baseline, for at least 3 out of the first 4 weeks of the treatment period. Weekly number of RFBMs were calculated as follows: 7 \* total number of RFBMs in a week/all non-missing assessment days in the given week. Weekly number of RFBMs was set to missing for any week when a participant completed less than (\<) 4 diary days in a week. A RFBM was a bowel movement without laxative use within 24 hrs prior to the bowel movement.

Outcome measures

Outcome measures
Measure	MNTX 150 mg n=201 Participants Participants received MNTX 150 mg (1 tablet of MNTX 150 mg and 2 matching placebo tablets) orally QD for 28 days (4 weeks), then MNTX tablets at a dose PRN for remaining 56 days (8 weeks).	MNTX 300 mg n=201 Participants Participants received 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 n=200 Participants Participants received 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 n=201 Participants Participants received 3 tablets of placebo matched to MNTX orally QD for 84 days (12 weeks).
Percentage of Participants Who Responded (Responder) to Study Drug During Weeks 1 to 4	45.3 percentage of participants	51.7 percentage of participants	54.5 percentage of participants	40.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 1 to 4

Population: ITT population included all randomized participants who received at least 1 dose of study drug. Missing data was imputed using LOCF method.

Weekly number of RFBMs were calculated as follows: 7 \* total number of RFBMs in a week/all non-missing assessment days in the given week. Weekly number of RFBMs was set to missing for any week when a participant completed less than (\<) 4 diary days in a week. A RFBM was a bowel movement without laxative use within 24 hrs prior to the bowel movement.

Outcome measures

Outcome measures
Measure	MNTX 150 mg n=201 Participants Participants received MNTX 150 mg (1 tablet of MNTX 150 mg and 2 matching placebo tablets) orally QD for 28 days (4 weeks), then MNTX tablets at a dose PRN for remaining 56 days (8 weeks).	MNTX 300 mg n=201 Participants Participants received 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 n=200 Participants Participants received 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 n=201 Participants Participants received 3 tablets of placebo matched to MNTX orally QD for 84 days (12 weeks).
Change in Weekly Number of RFBMs From Baseline Over the Entire First 4 Weeks (28 Days) of Dosing Baseline	1.46 RFBMs Standard Deviation 0.911	1.35 RFBMs Standard Deviation 0.891	1.37 RFBMs Standard Deviation 0.789	1.49 RFBMs Standard Deviation 1.045
Change in Weekly Number of RFBMs From Baseline Over the Entire First 4 Weeks (28 Days) of Dosing Change during Weeks 1-4	1.98 RFBMs Standard Deviation 2.139	2.43 RFBMs Standard Deviation 2.616	2.44 RFBMs Standard Deviation 2.515	1.87 RFBMs Standard Deviation 2.052

Adverse Events

MNTX 150 mg

Serious events: 5 serious events

Other events: 38 other events

Deaths: 0 deaths

MNTX 300 mg

Serious events: 6 serious events

Other events: 35 other events

Deaths: 0 deaths

MNTX 450 mg

Serious events: 4 serious events

Other events: 42 other events

Deaths: 0 deaths

Placebo

Serious events: 8 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	MNTX 150 mg n=201 participants at risk Participants received MNTX 150 mg (1 tablet of MNTX 150 mg and 2 matching placebo tablets) orally QD for 28 days (4 weeks), then MNTX tablets at a dose PRN for remaining 56 days (8 weeks).	MNTX 300 mg n=201 participants at risk Participants received 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 n=200 participants at risk Participants received 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 n=201 participants at risk Participants received 3 tablets of placebo matched to MNTX orally QD for 84 days (12 weeks).
Gastrointestinal disorders Abdominal pain	5.5% 11/201 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	8.0% 16/201 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	10.5% 21/200 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	8.5% 17/201 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Gastrointestinal disorders Diarrhoea	3.5% 7/201 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	6.5% 13/201 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	8.0% 16/200 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	3.5% 7/201 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Gastrointestinal disorders Flatulence	5.5% 11/201 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	3.5% 7/201 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	5.0% 10/200 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	4.5% 9/201 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Gastrointestinal disorders Nausea	6.5% 13/201 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	8.0% 16/201 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	6.0% 12/200 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	9.0% 18/201 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.
Musculoskeletal and connective tissue disorders Back pain	6.0% 12/201 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	3.0% 6/201 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	2.5% 5/200 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.	3.5% 7/201 • Baseline (Day 1) up to Day 98 Adverse events were collected by non-systematic (participant reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a participant reporting more than one adverse event for a particular MedDRA preferred term or system organ class was counted only once for that MedDRA preferred term or system organ class.

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.
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Restriction type: OTHER