Trial Outcomes & Findings for Opioid-induced Bowel Dysfunction: Pivotal Assessment of Lubiprostone (NCT NCT00595946)

NCT ID: NCT00595946

Last Updated: 2019-12-16

Results Overview

Spontaneous bowel movements (SBMs) are defined as bowel movements without the aid of drugs.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

439 participants

Primary outcome timeframe

at Week 8

Results posted on

2019-12-16

Participant Flow

Recruitment period: 03 August 2007 to 06 March 2009 Recruitment sites: 77 U.S. investigative sites and 3 Canadian investigative sites

Safety evaluable population, defined as all participants who were randomized and dosed, according to the product actually received.

Participant milestones

Participant milestones
Measure	Placebo Placebo : 0 mcg capsules twice daily (BID) for up to 12 weeks	Lubiprostone Lubiprostone : 24 mcg capsules twice daily (BID) for up to 12 weeks
Overall Study STARTED	218	221
Overall Study COMPLETED	154	152
Overall Study NOT COMPLETED	64	69

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Opioid-induced Bowel Dysfunction: Pivotal Assessment of Lubiprostone

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=217 Participants Placebo : 0 mcg capsules twice daily (BID)	Lubiprostone n=221 Participants Lubiprostone : 24 mcg capsules twice daily (BID)	Total n=438 Participants Total of all reporting groups
Age, Continuous	49.9 years STANDARD_DEVIATION 11.94 • n=5 Participants	50.1 years STANDARD_DEVIATION 9.89 • n=7 Participants	50.0 years STANDARD_DEVIATION 10.94 • n=5 Participants
Sex: Female, Male Female	144 Participants n=5 Participants	136 Participants n=7 Participants	280 Participants n=5 Participants
Sex: Female, Male Male	73 Participants n=5 Participants	85 Participants n=7 Participants	158 Participants n=5 Participants
Region of Enrollment United States	216 participants n=5 Participants	218 participants n=7 Participants	434 participants n=5 Participants
Region of Enrollment Canada	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants

PRIMARY outcome

Timeframe: at Week 8

Population: Per protocol population at Week 8 without dose reduction

Spontaneous bowel movements (SBMs) are defined as bowel movements without the aid of drugs.

Outcome measures

Outcome measures
Measure	Placebo n=169 Participants Placebo : 0 mcg capsules twice daily (BID)	Lubiprostone n=164 Participants Lubiprostone : 24 mcg capsules twice daily (BID)
Mean Weekly Spontaneous Bowel Movements at Week 8	2.4 SBMs/Week Standard Deviation 3.25	3.2 SBMs/Week Standard Deviation 3.35

SECONDARY outcome

Timeframe: within 12 weeks

Population: Intention to treat with scores at all 12 weeks

Average weekly SBM frequency was calculated from data collected from Week 1 through Week 12

Outcome measures

Outcome measures
Measure	Placebo n=216 Participants Placebo : 0 mcg capsules twice daily (BID)	Lubiprostone n=218 Participants Lubiprostone : 24 mcg capsules twice daily (BID)
Mean Number of Spontaneous Bowel Movements (SBM) Per Week Within 12 Weeks at Week 12	2.2 SBMs/Week Standard Deviation 3.26	2.8 SBMs/Week Standard Deviation 3.60
Mean Number of Spontaneous Bowel Movements (SBM) Per Week Within 12 Weeks within 12 weeks	2.1 SBMs/Week Standard Deviation 2.35	2.7 SBMs/Week Standard Deviation 2.59

SECONDARY outcome

Timeframe: within 48 hours post-dose

Population: Intention to treat

The number of participants who experienced their first post-dose Spontaneous Bowel Movement within 24 and 48 hours after dosing started.

Outcome measures

Outcome measures
Measure	Placebo n=217 Participants Placebo : 0 mcg capsules twice daily (BID)	Lubiprostone n=221 Participants Lubiprostone : 24 mcg capsules twice daily (BID)
Number of Participants With the First Post-dose Spontaneous Bowel Movement Within 48 Hours Post-dose within 24 hours	65 Participants	89 Participants
Number of Participants With the First Post-dose Spontaneous Bowel Movement Within 48 Hours Post-dose within 48 hours	116 Participants	138 Participants

SECONDARY outcome

Timeframe: within 12 weeks

Population: Intention to Treat

Number of participants who remained on treatment for at least 8 weeks, and reported at least 3 SBMs for at least half the weeks on study.

Outcome measures

Outcome measures
Measure	Placebo n=217 Participants Placebo : 0 mcg capsules twice daily (BID)	Lubiprostone n=221 Participants Lubiprostone : 24 mcg capsules twice daily (BID)
Number of Participants Classified as Responders	87 Participants	103 Participants

SECONDARY outcome

Timeframe: within 12 weeks

Population: Intention to Treat

Measures collected over 12-week treatment period were averaged, and the score at baseline was subtracted from the score at week 12 to determine the change from baseline. Straining scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe - higher scores are worse; Stool consistency scale: 0 = very loose, 1 = loose, 2 = normal, 3 = hard, 4 = very hard (little balls) - middle scores are best; Constipation severity scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe - higher scores are worse; Abdominal bloating scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe - higher scores are worse; Abdominal discomfort scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe - higher scores are worse; Bowel habit regularity scale: 7-point scale, where 1 = very regular and 7 = very irregular - higher scores are worse

Outcome measures

Outcome measures
Measure	Placebo n=217 Participants Placebo : 0 mcg capsules twice daily (BID)	Lubiprostone n=221 Participants Lubiprostone : 24 mcg capsules twice daily (BID)
Mean Change From Baseline in Straining, Stool Consistency, Constipation Severity, Abdominal Bloating, Abdominal Discomfort, and Bowel Habit Regularity Straining	-0.6 score on a scale Standard Deviation 0.88	-1.0 score on a scale Standard Deviation 1.00
Mean Change From Baseline in Straining, Stool Consistency, Constipation Severity, Abdominal Bloating, Abdominal Discomfort, and Bowel Habit Regularity Stool consistency	-0.5 score on a scale Standard Deviation 0.77	-0.8 score on a scale Standard Deviation 0.91
Mean Change From Baseline in Straining, Stool Consistency, Constipation Severity, Abdominal Bloating, Abdominal Discomfort, and Bowel Habit Regularity Constipation severity	-0.4 score on a scale Standard Deviation 0.71	-0.6 score on a scale Standard Deviation 0.74
Mean Change From Baseline in Straining, Stool Consistency, Constipation Severity, Abdominal Bloating, Abdominal Discomfort, and Bowel Habit Regularity Abdominal bloating	-0.4 score on a scale Standard Deviation 0.63	-0.4 score on a scale Standard Deviation 0.63
Mean Change From Baseline in Straining, Stool Consistency, Constipation Severity, Abdominal Bloating, Abdominal Discomfort, and Bowel Habit Regularity Abdominal discomfort	-0.3 score on a scale Standard Deviation 0.63	-0.5 score on a scale Standard Deviation 0.62
Mean Change From Baseline in Straining, Stool Consistency, Constipation Severity, Abdominal Bloating, Abdominal Discomfort, and Bowel Habit Regularity Bowel habit regularity	-0.5 score on a scale Standard Deviation 1.63	-0.6 score on a scale Standard Deviation 1.45

SECONDARY outcome

Timeframe: within 12 weeks

Population: Intention to Treat with all required scores

Participants rated treatment effectiveness at the end of each treatment week during the study on a 5-point scale, where 0 = not at all effective, 1 = a little bit effective, 2 = moderately effective, 3 = quite a bit effective, 4 = extremely effective. The 12 weekly scores were averaged. Higher scores mean the drug was more effective.

Outcome measures

Outcome measures
Measure	Placebo n=214 Participants Placebo : 0 mcg capsules twice daily (BID)	Lubiprostone n=211 Participants Lubiprostone : 24 mcg capsules twice daily (BID)
Participant Reported Outcome of Treatment Effectiveness	1.3 score on a scale Standard Deviation 0.99	1.6 score on a scale Standard Deviation 1.04

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 22 other events

Deaths: 0 deaths

Lubiprostone

Serious events: 12 serious events

Other events: 59 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=218 participants at risk Placebo : 0 mcg capsules twice daily (BID)	Lubiprostone n=221 participants at risk Lubiprostone : 24 mcg capsules twice daily (BID)
Gastrointestinal disorders Nausea	6.0% 13/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	15.8% 35/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Gastrointestinal disorders Diarrhoea	3.2% 7/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	9.5% 21/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Gastrointestinal disorders Abdominal distension	2.3% 5/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	7.7% 17/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.

Additional Information

Medical Information Call Center

Mallinckrodt

Phone: 800-556-3314

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Placebo n=218 participants at risk Placebo : 0 mcg capsules twice daily (BID)	Lubiprostone n=221 participants at risk Lubiprostone : 24 mcg capsules twice daily (BID)
Infections and infestations Gastroenteritis	0.46% 1/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.45% 1/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Infections and infestations Pneumonia	0.46% 1/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.00% 0/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Infections and infestations Cellulitis	0.00% 0/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.45% 1/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Infections and infestations Bronchitis	0.46% 1/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.00% 0/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Infections and infestations Appendicitis	0.46% 1/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.00% 0/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Psychiatric disorders Suicide Attempt	0.00% 0/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.45% 1/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Psychiatric disorders Postpartum depression	0.00% 0/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.45% 1/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Psychiatric disorders Bipolar disorder	0.00% 0/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.45% 1/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.46% 1/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.00% 0/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Musculoskeletal and connective tissue disorders Bursitis	0.46% 1/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.00% 0/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.45% 1/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.45% 1/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Gastrointestinal disorders Duodenal ulcer perforation	0.00% 0/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.45% 1/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Cardiac disorders Myocardial infarction	0.46% 1/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.00% 0/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Cardiac disorders Coronary artery disease	0.00% 0/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.45% 1/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Cardiac disorders Angina unstable	0.00% 0/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.45% 1/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.46% 1/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.00% 0/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Nervous system disorders Toxic encephalopathy	0.00% 0/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.45% 1/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.45% 1/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Injury, poisoning and procedural complications Ileum fracture	0.00% 0/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.45% 1/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.
Vascular disorders Hypertension	0.00% 0/218 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.	0.45% 1/221 • from time of first dose to 7 days after the final treatment (within 13 weeks) Treatment-emergent adverse events (TEAEs) are collected from participants based on the treatment actually received. TEAEs are defined as adverse events that began or got worse after the start of study drug. The safety evaluable population is based on the treatment actually received.