A Study of Oral Methylnaltrexone (MNTX) for the Treatment... | NCT01186770

Status Module

Name	Class
Progenics Pharmaceuticals, Inc.	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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).	Drug: Methylnaltrexone Drug: Placebo
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).	Drug: Methylnaltrexone Drug: Placebo
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).	Drug: Methylnaltrexone
Placebo	Placebo Comparator	Participants will receive 3 tablets of placebo matched to MNTX orally QD for 84 days (12 weeks).	Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Methylnaltrexone	Drug	Methylnaltrexone will be administered as per the dose and schedule specified in the respective arms.	MNTX 150 mg MNTX 300 mg MNTX 450 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Average Percentage of Dosing Days That Resulted in Rescue-Free Bowel Movements (RFBMs) Within 4 Hours of Dosing During Weeks 1 to 4	RFBM was defined as a bowel movement without laxative use within 24 hours prior to bowel movement.	Weeks 1 to 4

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants Who Responded (Responder) to Study Drug During Weeks 1 to 4	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.

Eligibility Module

Name	Affiliation	Role
Lindsey Mathew	Bausch Health Americas, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
PRA International		Raleigh	North Carolina	27612	United States
PRA, Intl.

PubMed Identifier	Type	Citation	Retractions
33788162	Derived	Liao SS, Slatkin NE, Stambler N. The Influence of Age on Central Effects of Methylnaltrexone in Patients with Opioid-Induced Constipation. Drugs Aging. 2021 Jun;38(6):503-511. doi: 10.1007/s40266-021-00850-w. Epub 2021 Mar 31.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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).
FG001	MNTX 300 mg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

ID	Title	Description
BG000	MNTX 150 mg	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).
BG001	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).
BG002	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).
BG003	Placebo	Participants received 3 tablets of placebo matched to MNTX orally QD for 84 days (12 weeks).
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG000201 BG001201 BG002200 BG003201 BG004803

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Average Percentage of Dosing Days That Resulted in Rescue-Free Bowel Movements (RFBMs) Within 4 Hours of Dosing During Weeks 1 to 4

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

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

Posted

Mean

Standard Deviation

percentage of days

Weeks 1 to 4

ID	Title	Description
OG000	MNTX 150 mg	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).
OG001	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).
OG002	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).
OG003	Placebo	Participants received 3 tablets of placebo matched to MNTX orally QD for 84 days (12 weeks).

Units	Counts
Participants	OG000201 OG001201 OG002200 OG003

Title

Denominators

Categories

Title	Measurements
	OG00021.05± 20.116 OG00124.64± 21.311 OG00227.40± 23.453 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG003	Analysis was performed using analysis of covariance (ANCOVA) with treatment as effect and analysis region as covariate.	ANCOVA		0.1692	Threshold for significance at 0.0167 level.	Least square (LS) mean difference	2.83				95	-1.21	6.86					Superiority
OG001 OG003

Secondary

Percentage of Participants Who Responded (Responder) to Study Drug During Weeks 1 to 4

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.

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.

Posted

Number

percentage of participants

Weeks 1 to 4

ID	Title	Description
OG000	MNTX 150 mg	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).
OG001	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).
OG002	MNTX 450 mg

Secondary

Change in Weekly Number of RFBMs From Baseline Over the Entire First 4 Weeks (28 Days) of Dosing

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.

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

Posted

Mean

Standard Deviation

RFBMs

Baseline, Weeks 1 to 4

ID	Title	Description
OG000	MNTX 150 mg	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).
OG001	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).
OG002	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).

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	MNTX 150 mg	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).	5	201	38	201
EG001	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).	6	201	35	201
EG002	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).	4	200	42	200
EG003	Placebo	Participants received 3 tablets of placebo matched to MNTX orally QD for 84 days (12 weeks).	8	201	32	201

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial flutter	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0010 affected201 at risk EG0020 affected200 at risk EG0031 affected201 at risk
Faecaloma	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0010 affected201 at risk EG0020 affected200 at risk EG003
Impaired gastric emptying	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0010 affected201 at risk EG0021 affected200 at risk EG003
Chest pain	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0011 affected201 at risk EG0020 affected200 at risk EG003
Drug withdrawal syndrome	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected201 at risk EG0010 affected201 at risk EG0020 affected200 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0010 affected201 at risk EG0020 affected200 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0010 affected201 at risk EG0020 affected200 at risk EG003
Bronchitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0010 affected201 at risk EG0021 affected200 at risk EG003
Cellulitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0010 affected201 at risk EG0021 affected200 at risk EG003
Enterocolitis infectious	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0010 affected201 at risk EG0020 affected200 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0011 affected201 at risk EG0020 affected200 at risk EG003
Influenza	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0010 affected201 at risk EG0020 affected200 at risk EG003
Osteomyelitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0010 affected201 at risk EG0020 affected200 at risk EG003
Pneumonia	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0011 affected201 at risk EG0020 affected200 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected201 at risk EG0010 affected201 at risk EG0020 affected200 at risk EG003
Overdose	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected201 at risk EG0010 affected201 at risk EG0020 affected200 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0011 affected201 at risk EG0020 affected200 at risk EG003
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0010 affected201 at risk EG0020 affected200 at risk EG003
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0010 affected201 at risk EG0020 affected200 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected201 at risk EG0010 affected201 at risk EG0020 affected200 at risk EG003
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0011 affected201 at risk EG0020 affected200 at risk EG003
Myositis ossificans	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0010 affected201 at risk EG0021 affected200 at risk EG003
Depression	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected201 at risk EG0010 affected201 at risk EG0020 affected200 at risk EG003
Suicidal ideation	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected201 at risk EG0011 affected201 at risk EG0020 affected200 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0011 affected201 at risk EG0020 affected200 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected201 at risk EG0010 affected201 at risk EG0020 affected200 at risk EG003
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0011 affected201 at risk EG0020 affected200 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0011 affected201 at risk EG0020 affected200 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected201 at risk EG0010 affected201 at risk EG0020 affected200 at risk EG003
Knee arthroplasty	Surgical and medical procedures	MedDRA 13.0	Systematic Assessment	EG0001 affected201 at risk EG0010 affected201 at risk EG0020 affected200 at risk EG003
Spinal fusion surgery	Surgical and medical procedures	MedDRA 13.0	Systematic Assessment	EG0000 affected201 at risk EG0010 affected201 at risk EG0020 affected200 at risk EG003

ID	Term
D003248	Constipation
D012817	Signs and Symptoms, Digestive
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D000079524	Narcotic-Related Disorders
D019966	Substance-Related Disorders
D064419	Chemically-Induced Disorders
D001523	Mental Disorders

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG00011 affected201 at risk EG00116 affected201 at risk EG00221 affected200 at risk EG00317 affected201 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0007 affected201 at risk EG00113 affected201 at risk EG00216 affected200 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG00011 affected201 at risk EG0017 affected201 at risk EG00210 affected200 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG00013 affected201 at risk EG00116 affected201 at risk EG00212 affected200 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG00012 affected201 at risk EG0016 affected201 at risk EG0025 affected200 at risk EG003