Trial Outcomes & Findings for Study Evaluating Subcutaneous Methylnaltrexone For Treatment Of Opioid-Induced Constipation In Patients With Advanced Illness (NCT NCT00672477)

Last Updated: 2018-03-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

237 participants

Primary outcome timeframe

7 days

Results posted on

2018-03-08

Participant Flow

Participant milestones

Participant milestones
Measure	Methylnaltrexone Bromide Methylnaltrexone bromide: Methylnaltrexone subcutaneously every other day for 14 days (ie, 7 doses).	Placebo Placebo: Placebo subcutaneously every other day for 14 days (ie, 7 doses).
Overall Study STARTED	116	114
Overall Study COMPLETED	89	88
Overall Study NOT COMPLETED	27	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Methylnaltrexone Bromide Methylnaltrexone bromide: Methylnaltrexone subcutaneously every other day for 14 days (ie, 7 doses).	Placebo Placebo: Placebo subcutaneously every other day for 14 days (ie, 7 doses).
Overall Study Adverse Event	10	7
Overall Study Death	7	11
Overall Study Physician Decision	2	0
Overall Study Protocol Violation	1	1
Overall Study Withdrawal by Subject	5	3
Overall Study Lack of Efficacy	1	1
Overall Study no study drug for low GFR, health cond.	1	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Methylnaltrexone Bromide n=116 Participants Methylnaltrexone bromide: Methylnaltrexone subcutaneously every other day for 14 days (ie, 7 doses).	Placebo n=114 Participants Placebo: Placebo subcutaneously every other day for 14 days (ie, 7 doses).	Total n=230 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	60 Participants n=5 Participants	57 Participants n=7 Participants	117 Participants n=5 Participants
Age, Categorical >=65 years	56 Participants n=5 Participants	57 Participants n=7 Participants	113 Participants n=5 Participants
Age, Continuous	65.31 years STANDARD_DEVIATION 12.92 • n=5 Participants	65.67 years STANDARD_DEVIATION 12.97 • n=7 Participants	65.49 years STANDARD_DEVIATION 12.92 • n=5 Participants
Sex: Female, Male Female	56 Participants n=5 Participants	58 Participants n=7 Participants	114 Participants n=5 Participants
Sex: Female, Male Male	60 Participants n=5 Participants	56 Participants n=7 Participants	116 Participants n=5 Participants
Underlying Advanced Illness Cancer	79 participants n=5 Participants	73 participants n=7 Participants	152 participants n=5 Participants
Underlying Advanced Illness Pulmonary disease (other than malignancy)	14 participants n=5 Participants	13 participants n=7 Participants	27 participants n=5 Participants
Underlying Advanced Illness Cardiovascular disease	13 participants n=5 Participants	11 participants n=7 Participants	24 participants n=5 Participants
Underlying Advanced Illness Neurologic disease	4 participants n=5 Participants	3 participants n=7 Participants	7 participants n=5 Participants
Underlying Advanced Illness Other	6 participants n=5 Participants	14 participants n=7 Participants	20 participants n=5 Participants
Weight < 62 kg	45 participants n=5 Participants	41 participants n=7 Participants	86 participants n=5 Participants
Weight ≥ 62 kg	71 participants n=5 Participants	73 participants n=7 Participants	144 participants n=5 Participants
Glomerular filtration rate < 30 mL/min/1.73 m^2	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Glomerular filtration rate ≥ 30 mL/min/1.73 m^2	110 participants n=5 Participants	108 participants n=7 Participants	218 participants n=5 Participants
Glomerular filtration rate Missing	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants

PRIMARY outcome

Timeframe: 7 days

Population: The analysis population included subjects who received ≥ 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Methylnaltrexone Bromide n=116 Participants Methylnaltrexone bromide: Methylnaltrexone subcutaneously every other day for 14 days (ie, 7 doses).	Placebo n=114 Participants Placebo: Placebo subcutaneously every other day for 14 days (ie, 7 doses).
The Proportion of Subjects Who Have a Rescue-free Laxation Response Within 4 Hours After at Least 2 of the First 4 Doses	62.9 percentage of participants Interval 53.5 to 71.7	9.6 percentage of participants Interval 4.9 to 16.6

SECONDARY outcome

Timeframe: 14 days

Population: The analysis population included subjects who received ≥ 1 dose of study drug.

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.

Outcome measures

Outcome measures
Measure	Methylnaltrexone Bromide n=116 Participants Methylnaltrexone bromide: Methylnaltrexone subcutaneously every other day for 14 days (ie, 7 doses).	Placebo n=114 Participants Placebo: Placebo subcutaneously every other day for 14 days (ie, 7 doses).
Time to First Rescue-free Laxation (Following the First Dose of Study Drug).	0.79 hours Interval 0.38 to 6.17	23.58 hours Interval 6.75 to 47.0

Adverse Events

Methylnaltrexone Bromide

Serious events: 14 serious events

Other events: 66 other events

Deaths: 0 deaths

Placebo

Serious events: 24 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Methylnaltrexone Bromide n=116 participants at risk Methylnaltrexone bromide: Methylnaltrexone subcutaneously every other day for 14 days (ie, 7 doses).	Placebo n=114 participants at risk Placebo: Placebo subcutaneously every other day for 14 days (ie, 7 doses).
Gastrointestinal disorders Abdominal pain	33.6% 39/116 • 14 days 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.	16.7% 19/114 • 14 days 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.
Gastrointestinal disorders Diarrhea	7.8% 9/116 • 14 days 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.	13.2% 15/114 • 14 days 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.
Gastrointestinal disorders Flatulence	6.9% 8/116 • 14 days 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.	4.4% 5/114 • 14 days 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.
Gastrointestinal disorders Nausea	11.2% 13/116 • 14 days 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.	14.9% 17/114 • 14 days 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.
Gastrointestinal disorders Vomiting	4.3% 5/116 • 14 days 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.	8.8% 10/114 • 14 days 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.
General disorders Edema peripheral	6.0% 7/116 • 14 days 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.	3.5% 4/114 • 14 days 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.
Injury, poisoning and procedural complications Fall	7.8% 9/116 • 14 days 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.	1.8% 2/114 • 14 days 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.
Musculoskeletal and connective tissue disorders Back pain	7.8% 9/116 • 14 days 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.	2.6% 3/114 • 14 days 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.
Psychiatric disorders Confusional state	6.0% 7/116 • 14 days 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.	7.9% 9/114 • 14 days 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.

Additional Information

David Sorscher

Salix

Phone: 919-862-1827

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Methylnaltrexone Bromide n=116 participants at risk Methylnaltrexone bromide: Methylnaltrexone subcutaneously every other day for 14 days (ie, 7 doses).	Placebo n=114 participants at risk Placebo: Placebo subcutaneously every other day for 14 days (ie, 7 doses).
Blood and lymphatic system disorders Anemia	0.00% 0/116 • 14 days 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.	0.88% 1/114 • 14 days 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.
Cardiac disorders Cardiac failure congestive	0.00% 0/116 • 14 days 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.	0.88% 1/114 • 14 days 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.
Cardiac disorders Coronary artery disease	0.00% 0/116 • 14 days 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.	0.88% 1/114 • 14 days 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.
Gastrointestinal disorders Constipation	0.00% 0/116 • 14 days 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.	0.88% 1/114 • 14 days 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.
General disorders Disease progression	7.8% 9/116 • 14 days 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.	12.3% 14/114 • 14 days 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.
Injury, poisoning and procedural complications Fall	0.00% 0/116 • 14 days 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.	1.8% 2/114 • 14 days 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.
Metabolism and nutrition disorders Hypercalcemia	0.86% 1/116 • 14 days 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.	0.00% 0/114 • 14 days 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.
Metabolism and nutrition disorders Hyponatremia	0.86% 1/116 • 14 days 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.	0.88% 1/114 • 14 days 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.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/116 • 14 days 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.	0.88% 1/114 • 14 days 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.
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/116 • 14 days 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.	0.88% 1/114 • 14 days 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer metastatic	0.86% 1/116 • 14 days 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.	0.00% 0/114 • 14 days 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.
Nervous system disorders Spinal cord compression	0.00% 0/116 • 14 days 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.	1.8% 2/114 • 14 days 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.
Psychiatric disorders Delirium	0.00% 0/116 • 14 days 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.	0.88% 1/114 • 14 days 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.
Psychiatric disorders Disorientation	0.00% 0/116 • 14 days 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.	0.88% 1/114 • 14 days 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.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/116 • 14 days 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.	0.88% 1/114 • 14 days 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.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/116 • 14 days 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.	0.88% 1/114 • 14 days 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.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/116 • 14 days 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.	0.88% 1/114 • 14 days 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.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/116 • 14 days 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.	0.88% 1/114 • 14 days 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.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.00% 0/116 • 14 days 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.	0.88% 1/114 • 14 days 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.
Vascular disorders Deep vein thrombosis	0.00% 0/116 • 14 days 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.	0.88% 1/114 • 14 days 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.
Gastrointestinal disorders Gastric ulcer perforation	0.86% 1/116 • 14 days 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.	0.00% 0/114 • 14 days 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.
Gastrointestinal disorders Intestinal obstruction	0.86% 1/116 • 14 days 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.	0.00% 0/114 • 14 days 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.
Gastrointestinal disorders Nausea	0.00% 0/116 • 14 days 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.	0.88% 1/114 • 14 days 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.