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Study Evaluating Subcutaneous Methylnaltrexone For Treatment Of Opioid-Induced Constipation In Patients With Advanced Illness

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ClinicalTrials.gov Identifier: NCT00672477
Recruitment Status : Completed
First Posted : May 6, 2008
Results First Posted : March 8, 2018
Last Update Posted : March 8, 2018
Sponsor:
Collaborator:
Progenics Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Bausch Health Americas, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Opioid-Induced Constipation
Interventions Drug: Methylnaltrexone
Drug: Placebo
Enrollment 237
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Methylnaltrexone Bromide Placebo
Hide Arm/Group Description Methylnaltrexone bromide: Methylnaltrexone subcutaneously every other day for 14 days (ie, 7 doses). Placebo: Placebo subcutaneously every other day for 14 days (ie, 7 doses).
Period Title: Overall Study
Started 116 [1] 114 [2]
Completed 89 [3] 88
Not Completed 27 26
Reason Not Completed
Adverse Event             10             7
Death             7             11
Physician Decision             2             0
Protocol Violation             1             1
Withdrawal by Subject             5             3
Lack of Efficacy             1             1
no study drug for low GFR, health cond.             1             3
[1]
120 subjects were randomized to this group, but only 116 subjects received study drug.
[2]
117 subjects were randomized to this group, but only 114 subjects received study drug.
[3]
One subject had missing data as reason for study termination - not counted as early termination.
Arm/Group Title Methylnaltrexone Bromide Placebo Total
Hide Arm/Group Description Methylnaltrexone bromide: Methylnaltrexone subcutaneously every other day for 14 days (ie, 7 doses). Placebo: Placebo subcutaneously every other day for 14 days (ie, 7 doses). Total of all reporting groups
Overall Number of Baseline Participants 116 114 230
Hide Baseline Analysis Population Description
The analysis population included subjects who received ≥ 1 dose of study drug.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 116 participants 114 participants 230 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
60
  51.7%
57
  50.0%
117
  50.9%
>=65 years
56
  48.3%
57
  50.0%
113
  49.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 116 participants 114 participants 230 participants
65.31  (12.92) 65.67  (12.97) 65.49  (12.92)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 116 participants 114 participants 230 participants
Female
56
  48.3%
58
  50.9%
114
  49.6%
Male
60
  51.7%
56
  49.1%
116
  50.4%
Underlying Advanced Illness  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 116 participants 114 participants 230 participants
Cancer 79 73 152
Pulmonary disease (other than malignancy) 14 13 27
Cardiovascular disease 13 11 24
Neurologic disease 4 3 7
Other 6 14 20
Weight  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 116 participants 114 participants 230 participants
< 62 kg 45 41 86
≥ 62 kg 71 73 144
Glomerular filtration rate  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 116 participants 114 participants 230 participants
< 30 mL/min/1.73 m^2 3 3 6
≥ 30 mL/min/1.73 m^2 110 108 218
Missing 3 3 6
1.Primary Outcome
Title The Proportion of Subjects Who Have a Rescue-free Laxation Response Within 4 Hours After at Least 2 of the First 4 Doses
Hide Description This outcome measures the proportion of subjects who had a rescue-free laxation (ie, bowel movement) within 4 hours after at least 2 of the first 4 doses of study drug. A "rescue free" laxation was defined as a laxation without use of any rescue medication or rescue procedures within 4 hours prior to the laxation.
Time Frame 7 days
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included subjects who received ≥ 1 dose of study drug.
Arm/Group Title Methylnaltrexone Bromide Placebo
Hide Arm/Group Description:
Methylnaltrexone bromide: Methylnaltrexone subcutaneously every other day for 14 days (ie, 7 doses).
Placebo: Placebo subcutaneously every other day for 14 days (ie, 7 doses).
Overall Number of Participants Analyzed 116 114
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
62.9
(53.5 to 71.7)
9.6
(4.9 to 16.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methylnaltrexone Bromide, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
2.Secondary Outcome
Title Time to First Rescue-free Laxation (Following the First Dose of Study Drug).
Hide Description This outcome measures the time from first dose of study drug to the first rescue-free laxation (ie, bowel movement). A "rescue free" laxation was defined as a laxation without use of any rescue medication or rescue procedures within 4 hours prior to the laxation.
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included subjects who received ≥ 1 dose of study drug.
Arm/Group Title Methylnaltrexone Bromide Placebo
Hide Arm/Group Description:
Methylnaltrexone bromide: Methylnaltrexone subcutaneously every other day for 14 days (ie, 7 doses).
Placebo: Placebo subcutaneously every other day for 14 days (ie, 7 doses).
Overall Number of Participants Analyzed 116 114
Median (Inter-Quartile Range)
Unit of Measure: hours
0.79
(0.38 to 6.17)
23.58
(6.75 to 47.00)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Methylnaltrexone Bromide, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Time Frame 14 days
Adverse Event Reporting Description Adverse events were collected by non-systematic (patient reports) and systematic methods (investigator examinations and lab tests). For both adverse events tables, a subject 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.
 
Arm/Group Title Methylnaltrexone Bromide Placebo
Hide Arm/Group Description Methylnaltrexone bromide: Methylnaltrexone subcutaneously every other day for 14 days (ie, 7 doses). Placebo: Placebo subcutaneously every other day for 14 days (ie, 7 doses).
All-Cause Mortality
Methylnaltrexone Bromide Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Methylnaltrexone Bromide Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   14/116 (12.07%)   24/114 (21.05%) 
Blood and lymphatic system disorders     
Anemia  1  0/116 (0.00%)  1/114 (0.88%) 
Cardiac disorders     
Cardiac failure congestive  1  0/116 (0.00%)  1/114 (0.88%) 
Coronary artery disease  1  0/116 (0.00%)  1/114 (0.88%) 
Gastrointestinal disorders     
Constipation  1  0/116 (0.00%)  1/114 (0.88%) 
Gastric ulcer perforation  1  1/116 (0.86%)  0/114 (0.00%) 
Intestinal obstruction  1  1/116 (0.86%)  0/114 (0.00%) 
Nausea  1  0/116 (0.00%)  1/114 (0.88%) 
General disorders     
Disease progression  1  9/116 (7.76%)  14/114 (12.28%) 
Injury, poisoning and procedural complications     
Fall  1  0/116 (0.00%)  2/114 (1.75%) 
Metabolism and nutrition disorders     
Hypercalcemia  1  1/116 (0.86%)  0/114 (0.00%) 
Hyponatremia  1  1/116 (0.86%)  1/114 (0.88%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  0/116 (0.00%)  1/114 (0.88%) 
Pathological fracture  1  0/116 (0.00%)  1/114 (0.88%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Colon cancer metastatic  1  1/116 (0.86%)  0/114 (0.00%) 
Nervous system disorders     
Spinal cord compression  1  0/116 (0.00%)  2/114 (1.75%) 
Psychiatric disorders     
Delirium  1  0/116 (0.00%)  1/114 (0.88%) 
Disorientation  1  0/116 (0.00%)  1/114 (0.88%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  0/116 (0.00%)  1/114 (0.88%) 
Dyspnea  1  0/116 (0.00%)  1/114 (0.88%) 
Epistaxis  1  0/116 (0.00%)  1/114 (0.88%) 
Pneumonia aspiration  1  0/116 (0.00%)  1/114 (0.88%) 
Respiratory arrest  1  0/116 (0.00%)  1/114 (0.88%) 
Vascular disorders     
Deep vein thrombosis  1  0/116 (0.00%)  1/114 (0.88%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version 14.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Methylnaltrexone Bromide Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   66/116 (56.90%)   52/114 (45.61%) 
Gastrointestinal disorders     
Abdominal pain  1  39/116 (33.62%)  19/114 (16.67%) 
Diarrhea  1  9/116 (7.76%)  15/114 (13.16%) 
Flatulence  1  8/116 (6.90%)  5/114 (4.39%) 
Nausea  1  13/116 (11.21%)  17/114 (14.91%) 
Vomiting  1  5/116 (4.31%)  10/114 (8.77%) 
General disorders     
Edema peripheral  1  7/116 (6.03%)  4/114 (3.51%) 
Injury, poisoning and procedural complications     
Fall  1  9/116 (7.76%)  2/114 (1.75%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  9/116 (7.76%)  3/114 (2.63%) 
Psychiatric disorders     
Confusional state  1  7/116 (6.03%)  9/114 (7.89%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version 14.0
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: David Sorscher
Organization: Salix
Phone: 919-862-1827
EMail: david.sorscher@salix.com
Layout table for additonal information
Responsible Party: Bausch Health Americas, Inc.
ClinicalTrials.gov Identifier: NCT00672477    
Other Study ID Numbers: 3200K1-4000
B2541005
First Submitted: May 2, 2008
First Posted: May 6, 2008
Results First Submitted: February 7, 2018
Results First Posted: March 8, 2018
Last Update Posted: March 8, 2018