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Study Evaluating Long-Term Safety of MOA-728 in Participants With Opioid-Induced Constipation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00804141
Recruitment Status : Completed
First Posted : December 8, 2008
Results First Posted : October 18, 2019
Last Update Posted : October 18, 2019
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Bausch Health Americas, Inc.

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Constipation
Intervention Drug: N-methylnaltrexone bromide (MOA-728)
Enrollment 1040
Recruitment Details  
Pre-assignment Details A total of 1040 participants who met the inclusion/exclusion criteria were assigned to receive treatment and 1034 of these participants received at least 1 dose of study drug.
Arm/Group Title MOA-728 12 mg QD
Hide Arm/Group Description Participants received N-methylnaltrexone bromide (MOA-728, MNTX) 12 milligrams (mg) subcutaneously (SC) once daily (QD) for 48 weeks. Dosing could be adjusted to an as needed (PRN) basis with a minimum 1 dose per week and maximum 1 dose per day.
Period Title: Overall Study
Started 1040
Received at Least 1 Dose of Study Drug 1034
Completed 477
Not Completed 563
Reason Not Completed
Adverse Event             157
Death             4
Failed to return             96
Investigator request             8
Protocol Violation             85
Withdrawal by Subject             131
Lack of Efficacy             46
Other than specified             30
Enrolled but not treated             6
Arm/Group Title MOA-728 12 mg QD
Hide Arm/Group Description Participants received MOA-728 12 mg SC QD for 48 weeks. Dosing could be adjusted to PRN basis with a minimum 1 dose per week and maximum 1 dose per day.
Overall Number of Baseline Participants 1034
Hide Baseline Analysis Population Description
All participants who received at least one dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1034 participants
51.67  (10.84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1034 participants
Female
669
  64.7%
Male
365
  35.3%
1.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Hide Description Adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Serious adverse events (SAEs) included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as an AE that emerged during the treatment period. Any TEAEs included both treatment-emergent SAEs and non-serious AEs. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Time Frame Baseline up to Week 50
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug.
Arm/Group Title MOA-728 12 mg QD
Hide Arm/Group Description:
Participants received MOA-728 12 mg SC QD for 48 weeks. Dosing could be adjusted to PRN basis with a minimum 1 dose per week and maximum 1 dose per day.
Overall Number of Participants Analyzed 1034
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAEs
817
  79.0%
SAEs
104
  10.1%
2.Secondary Outcome
Title Change From Baseline in Weekly Bowel Movement (BM) Rate Through Follow-up
Hide Description Weekly BM rate was derived as the total number of BMs reported in a month divided by the total number of days with non-missing BM diary information in the same month, then multiplied by 7 to normalize to a weekly rate. If the total number of days with non-missing BM diary information in a given month was less than 10 days, the weekly BM rate for the month was defined as missing. The weekly BM rate at baseline was calculated based on the screening period (Days -14 to -1). If the total number of days with non-missing BM diary information during the screening period was less than 5 days, the weekly BM rate at baseline was defined as missing.
Time Frame Baseline, follow-up (14 days [Week 49 to 50])
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug. Here, 'Number analyzed' signifies participants evaluable at specified timepoint.
Arm/Group Title MOA-728 12 mg QD
Hide Arm/Group Description:
Participants received MOA-728 12 mg SC QD for 48 weeks. Dosing could be adjusted to PRN basis with a minimum 1 dose per week and maximum 1 dose per day.
Overall Number of Participants Analyzed 1034
Mean (Standard Deviation)
Unit of Measure: BM/week
Baseline Number Analyzed 1034 participants
3.9  (2.8)
Change during follow-up Number Analyzed 529 participants
0.5  (2.7)
Time Frame Baseline up to Week 50
Adverse Event Reporting Description All participants who received at least one dose of study drug.
 
Arm/Group Title MOA-728 12 mg QD
Hide Arm/Group Description Participants received MOA-728 12 mg SC QD for 48 weeks. Dosing could be adjusted to PRN basis with a minimum 1 dose per week and maximum 1 dose per day.
All-Cause Mortality
MOA-728 12 mg QD
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
MOA-728 12 mg QD
Affected / at Risk (%)
Total   104/1034 (10.06%) 
Blood and lymphatic system disorders   
Leukocytosis  1  1/1034 (0.10%) 
Lymphadenopathy  1  1/1034 (0.10%) 
Cardiac disorders   
Angina pectoris  1  3/1034 (0.29%) 
Cardiac arrest  1  1/1034 (0.10%) 
Cardiac failure congestive  1  1/1034 (0.10%) 
Coronary artery disease  1  2/1034 (0.19%) 
Myocardial infarction  1  4/1034 (0.39%) 
Prinzmetal angina  1  1/1034 (0.10%) 
Eye disorders   
Choroiditis  1  1/1034 (0.10%) 
Ulcerative keratitis  1  1/1034 (0.10%) 
Vision blurred  1  1/1034 (0.10%) 
Gastrointestinal disorders   
Abdominal pain  1  4/1034 (0.39%) 
Abdominal pain lower  1  1/1034 (0.10%) 
Abdominal pain upper  1  1/1034 (0.10%) 
Colitis  1  2/1034 (0.19%) 
Diarrhoea  1  4/1034 (0.39%) 
Faecal incontinence  1  1/1034 (0.10%) 
Gastrooesophageal reflux disease  1  1/1034 (0.10%) 
Haematochezia  1  1/1034 (0.10%) 
Intestinal obstruction  1  2/1034 (0.19%) 
Localised intraabdominal fluid collection  1  1/1034 (0.10%) 
Lower gastrointestinal haemorrhage  1  1/1034 (0.10%) 
Lumbar hernia  1  1/1034 (0.10%) 
Nausea  1  3/1034 (0.29%) 
Oesophageal achalasia  1  1/1034 (0.10%) 
Oesophageal dilatation  1  1/1034 (0.10%) 
Pancreatitis  1  1/1034 (0.10%) 
Pancreatitis acute  1  1/1034 (0.10%) 
Small intestinal obstruction  1  2/1034 (0.19%) 
Vomiting  1  2/1034 (0.19%) 
General disorders   
Abasia  1  1/1034 (0.10%) 
Asthenia  1  1/1034 (0.10%) 
Chills  1  1/1034 (0.10%) 
Device dislocation  1  1/1034 (0.10%) 
Fatigue  1  1/1034 (0.10%) 
Non-cardiac chest pain  1  4/1034 (0.39%) 
Oedema peripheral  1  1/1034 (0.10%) 
Pain  1  1/1034 (0.10%) 
Sudden death  1  1/1034 (0.10%) 
Hepatobiliary disorders   
Cholecystitis  1  1/1034 (0.10%) 
Cholecystitis acute  1  1/1034 (0.10%) 
Cholelithiasis  1  1/1034 (0.10%) 
Gallbladder disorder  1  1/1034 (0.10%) 
Jaundice  1  1/1034 (0.10%) 
Immune system disorders   
Polyarteritis nodosa  1  1/1034 (0.10%) 
Infections and infestations   
Appendicitis  1  1/1034 (0.10%) 
Bronchitis  1  1/1034 (0.10%) 
Bronchopneumonia  1  2/1034 (0.19%) 
Cellulitis  1  2/1034 (0.19%) 
Device related infection  1  1/1034 (0.10%) 
Diverticulitis  1  1/1034 (0.10%) 
Gastroenteritis  1  2/1034 (0.19%) 
Gastroenteritis viral  1  1/1034 (0.10%) 
Lower respiratory tract infection  1  1/1034 (0.10%) 
Perihepatic abscess  1  1/1034 (0.10%) 
Pneumonia  1  8/1034 (0.77%) 
Pyelonephritis  1  1/1034 (0.10%) 
Sepsis  1  1/1034 (0.10%) 
Septic shock  1  1/1034 (0.10%) 
Staphylococcal skin infection  1  1/1034 (0.10%) 
Upper respiratory tract infection  1  1/1034 (0.10%) 
Urinary tract infection  1  1/1034 (0.10%) 
Wound infection staphylococcal  1  1/1034 (0.10%) 
Injury, poisoning and procedural complications   
Accidental overdose  1  1/1034 (0.10%) 
Fibula fracture  1  1/1034 (0.10%) 
In-stent coronary artery restenosis  1  1/1034 (0.10%) 
Intentional overdose  1  1/1034 (0.10%) 
Lower limb fracture  1  1/1034 (0.10%) 
Multiple fractures  1  1/1034 (0.10%) 
Overdose  1  1/1034 (0.10%) 
Post procedural bile leak  1  1/1034 (0.10%) 
Post procedural haemorrhage  1  1/1034 (0.10%) 
Road traffic accident  1  1/1034 (0.10%) 
Spinal compression fracture  1  1/1034 (0.10%) 
Traumatic liver injury  1  1/1034 (0.10%) 
Investigations   
Blood potassium decreased  1  1/1034 (0.10%) 
Nuclear magnetic resonance imaging abnormal  1  1/1034 (0.10%) 
Metabolism and nutrition disorders   
Decreased appetite  1  1/1034 (0.10%) 
Dehydration  1  3/1034 (0.29%) 
Hyperkalaemia  1  1/1034 (0.10%) 
Hypokalaemia  1  1/1034 (0.10%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  1/1034 (0.10%) 
Back pain  1  5/1034 (0.48%) 
Intervertebral disc protrusion  1  1/1034 (0.10%) 
Muscular weakness  1  1/1034 (0.10%) 
Musculoskeletal pain  1  2/1034 (0.19%) 
Neck pain  1  1/1034 (0.10%) 
Scoliosis  1  1/1034 (0.10%) 
Spinal column stenosis  1  1/1034 (0.10%) 
Spinal osteoarthritis  1  1/1034 (0.10%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Breast cancer  1  1/1034 (0.10%) 
Thyroid neoplasm  1  1/1034 (0.10%) 
Nervous system disorders   
Cerebrovascular accident  1  1/1034 (0.10%) 
Convulsion  1  1/1034 (0.10%) 
Dizziness  1  1/1034 (0.10%) 
Dysarthria  1  1/1034 (0.10%) 
Head discomfort  1  1/1034 (0.10%) 
Hypoaesthesia  1  4/1034 (0.39%) 
Migraine  1  1/1034 (0.10%) 
Nerve compression  1  1/1034 (0.10%) 
Neuralgia  1  2/1034 (0.19%) 
Radiculopathy  1  1/1034 (0.10%) 
Syncope  1  1/1034 (0.10%) 
Pregnancy, puerperium and perinatal conditions   
Abortion spontaneous  1  1/1034 (0.10%) 
Pregnancy  1  3/1034 (0.29%) 
Psychiatric disorders   
Alcohol abuse  1  1/1034 (0.10%) 
Depression  1  2/1034 (0.19%) 
Intentional drug misuse  1  1/1034 (0.10%) 
Major depression  1  2/1034 (0.19%) 
Mental status changes  1  1/1034 (0.10%) 
Suicidal ideation  1  1/1034 (0.10%) 
Renal and urinary disorders   
Renal failure  1  2/1034 (0.19%) 
Renal failure acute  1  1/1034 (0.10%) 
Reproductive system and breast disorders   
Dysfunctional uterine bleeding  1 [1]  1/669 (0.15%) 
Respiratory, thoracic and mediastinal disorders   
Acute respiratory failure  1  1/1034 (0.10%) 
Asthma  1  4/1034 (0.39%) 
Atelectasis  1  1/1034 (0.10%) 
Bronchial hyperreactivity  1  1/1034 (0.10%) 
Chronic obstructive pulmonary disease  1  4/1034 (0.39%) 
Dyspnoea  1  2/1034 (0.19%) 
Pleural effusion  1  1/1034 (0.10%) 
Pulmonary embolism  1  1/1034 (0.10%) 
Respiratory distress  1  1/1034 (0.10%) 
Skin and subcutaneous tissue disorders   
Granuloma skin  1  1/1034 (0.10%) 
Surgical and medical procedures   
Shoulder arthroplasty  1  1/1034 (0.10%) 
Vascular disorders   
Hypertension  1  2/1034 (0.19%) 
Hypotension  1  2/1034 (0.19%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
[1]
This is a gender-specific AE. Only female participants were at risk.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
MOA-728 12 mg QD
Affected / at Risk (%)
Total   564/1034 (54.55%) 
Gastrointestinal disorders   
Abdominal pain  1  248/1034 (23.98%) 
Abdominal pain upper  1  69/1034 (6.67%) 
Diarrhoea  1  171/1034 (16.54%) 
Nausea  1  158/1034 (15.28%) 
Flatulence  1  57/1034 (5.51%) 
Vomiting  1  77/1034 (7.45%) 
Infections and infestations   
Influenza  1  64/1034 (6.19%) 
Sinusitis  1  56/1034 (5.42%) 
Upper respiratory tract infection  1  61/1034 (5.90%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  65/1034 (6.29%) 
Nervous system disorders   
Headache  1  60/1034 (5.80%) 
Skin and subcutaneous tissue disorders   
Hyperhidrosis  1  93/1034 (8.99%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Please contact Sponsor directly for additional information.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director of Clinical Operations
Organization: Bausch Health Americas, Inc
EMail: Lindsey.Mathew@bauschhealth.com
Publications of Results:
Webster R, Michna E, Khan A, et al., The long-term efficacy of subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with chronic nonmalignant pain. J. Pain, 12(4), Supplement , Page P70, April 2011
Layout table for additonal information
Responsible Party: Bausch Health Americas, Inc.
ClinicalTrials.gov Identifier: NCT00804141    
Other Study ID Numbers: 3200K1-3358
First Submitted: December 5, 2008
First Posted: December 8, 2008
Results First Submitted: September 27, 2019
Results First Posted: October 18, 2019
Last Update Posted: October 18, 2019