Trial Outcomes & Findings for Opioid-induced Bowel Dysfunction Pivotal Assessment of Lubiprostone (NCT NCT00597428)

NCT ID: NCT00597428

Last Updated: 2019-12-10

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 437 participants
• Primary outcome timeframe: Baseline and Week 8
• Results posted on: 2019-12-10

Participant Flow

Recruitment period: 06 August 2007 through 06 March 2009 Recruitment sites: 84 U.S. investigative sites and 4 Canadian investigative sites

Safety evaluable population (listed below under 'Started') includes all subjects who randomized and dosed. NOTE: these numbers are based on 1 miss randomized subjects - randomized to Lubiprostone and received Placebo. ITT population includes only those subjects who dosed and provided at least one post-treatment efficacy assessment.

Participant milestones

Measure	Placebo Placebo : 0 mcg capsules twice daily (BID) for 12 weeks	Lubiprostone Lubiprostone : 24 mcg capsules twice daily (BID) for 12 weeks
Overall Study STARTED	214	223
Overall Study COMPLETED	153	152
Overall Study NOT COMPLETED	61	71

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Opioid-induced Bowel Dysfunction Pivotal Assessment of Lubiprostone

Baseline characteristics by cohort

Measure	Placebo n=212 Participants Placebo : 0 mcg capsules twice daily (BID)	Lubiprostone n=223 Participants Lubiprostone : 24 mcg capsules twice daily (BID)	Total n=435 Participants Total of all reporting groups
Age, Continuous	49.8 years STANDARD_DEVIATION 10.44 • n=5 Participants	48.9 years STANDARD_DEVIATION 9.85 • n=7 Participants	49.4 years STANDARD_DEVIATION 10.14 • n=5 Participants
Sex: Female, Male Female	126 Participants n=5 Participants	140 Participants n=7 Participants	266 Participants n=5 Participants
Sex: Female, Male Male	86 Participants n=5 Participants	83 Participants n=7 Participants	169 Participants n=5 Participants
Region of Enrollment United States	207 participants n=5 Participants	219 participants n=7 Participants	426 participants n=5 Participants
Region of Enrollment Canada	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8

Outcome measures

Measure	Placebo n=212 Participants Placebo : 0 mcg capsules twice daily (BID)	Lubiprostone n=223 Participants Lubiprostone : 24 mcg capsules twice daily (BID)
Change From Baseline in Mean Weekly Spontaneous Bowel Movement (SBM) Frequency in Subjects Without Dose Reduction Prior to Week 8	2.4 Spontaneous Bowel Movements/Week Standard Deviation 3.20	2.6 Spontaneous Bowel Movements/Week Standard Deviation 3.26

SECONDARY outcome

Timeframe: Baseline, Week 12, and Weeks 1-12

For overall assessment of change, average weekly rating was calculated from data collected from Week 1 through Week 12.

Outcome measures

Measure	Placebo n=209 Participants Placebo : 0 mcg capsules twice daily (BID)	Lubiprostone n=217 Participants Lubiprostone : 24 mcg capsules twice daily (BID)
Change From Baseline in Mean Weekly SBM Frequency Week 12	2.6 Spontaneous Bowel Movements/Week Standard Deviation 3.57	2.5 Spontaneous Bowel Movements/Week Standard Deviation 3.64
Change From Baseline in Mean Weekly SBM Frequency Overall	2.3 Spontaneous Bowel Movements/Week Standard Deviation 2.57	2.6 Spontaneous Bowel Movements/Week Standard Deviation 2.73

SECONDARY outcome

Timeframe: 24 and 48 hours post-dose

The number of participants that experienced first post-dose SBM 24 and 48 hour of dose initiation.

Outcome measures

Measure	Placebo n=212 Participants Placebo : 0 mcg capsules twice daily (BID)	Lubiprostone n=223 Participants Lubiprostone : 24 mcg capsules twice daily (BID)
First Post-dose SBM 24 hours	64 participants	74 participants
First Post-dose SBM 48 hours	118 participants	136 participants

SECONDARY outcome

Timeframe: Up to 12 weeks

Number of participants, who remained on treatment for at least 8 weeks, and reported response (>=3 SBMs) for at least 50% of weeks on study.

Outcome measures

Measure	Placebo n=212 Participants Placebo : 0 mcg capsules twice daily (BID)	Lubiprostone n=223 Participants Lubiprostone : 24 mcg capsules twice daily (BID)
Responder Rate	100 participants	108 participants

SECONDARY outcome

Timeframe: Weeks 1-12

Ratings over 12-week treatment period were averaged and difference from baseline score calculated Straining scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe Stool consistency scale: 0 = very loose, 1 = loose, 2 = normal, 3 = hard, 4 = very hard (little balls) Constipation severity scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe Abdominal bloating scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe Abdominal discomfort scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe Bowel habit regularity scale: 7-point scale, where 1 = very regular and 7 = very irregular

Outcome measures

Measure	Placebo n=212 Participants Placebo : 0 mcg capsules twice daily (BID)	Lubiprostone n=223 Participants Lubiprostone : 24 mcg capsules twice daily (BID)
Mean Changes From Baseline in Straining, Stool Consistency, Constipation Severity, Abdominal Bloating, Abdominal Discomfort, and Bowel Habit Regularity Straining	-0.5 units on a scale Standard Deviation 0.89	-0.8 units on a scale Standard Deviation 0.96
Mean Changes From Baseline in Straining, Stool Consistency, Constipation Severity, Abdominal Bloating, Abdominal Discomfort, and Bowel Habit Regularity Stool consistency	-0.4 units on a scale Standard Deviation 0.81	-0.6 units on a scale Standard Deviation 0.84
Mean Changes From Baseline in Straining, Stool Consistency, Constipation Severity, Abdominal Bloating, Abdominal Discomfort, and Bowel Habit Regularity Constipation severity	-0.5 units on a scale Standard Deviation 0.72	-0.6 units on a scale Standard Deviation 0.79
Mean Changes From Baseline in Straining, Stool Consistency, Constipation Severity, Abdominal Bloating, Abdominal Discomfort, and Bowel Habit Regularity Abdominal bloating	-0.4 units on a scale Standard Deviation 0.64	-0.5 units on a scale Standard Deviation 0.70
Mean Changes From Baseline in Straining, Stool Consistency, Constipation Severity, Abdominal Bloating, Abdominal Discomfort, and Bowel Habit Regularity Abdominal discomfort	-0.4 units on a scale Standard Deviation 0.64	-0.5 units on a scale Standard Deviation 0.69
Mean Changes From Baseline in Straining, Stool Consistency, Constipation Severity, Abdominal Bloating, Abdominal Discomfort, and Bowel Habit Regularity Bowel habit regularity	-0.6 units on a scale Standard Deviation 1.57	-0.8 units on a scale Standard Deviation 1.57

SECONDARY outcome

Timeframe: Weeks 1-12

Population: Treatment effectiveness scores were collected at the end of each treatment week during the study; the number of participants analyzed reflects those subjects who provided at least one end-of-week assessment of treatment effectiveness. For the analysis, treatment effectiveness scores were averaged across the treatment period (Weeks 1-12).

Treatment effectiveness scale: 0 = not at all effective, 1 = a little bit effective, 2 = moderately effective, 3 = quite a bit effective, 4 = extremely effective

Outcome measures

Measure	Placebo n=201 Participants Placebo : 0 mcg capsules twice daily (BID)	Lubiprostone n=213 Participants Lubiprostone : 24 mcg capsules twice daily (BID)
Treatment Effectiveness	1.4 units on a scale Standard Deviation 1.04	1.5 units on a scale Standard Deviation 1.07

Adverse Events

Placebo

Serious events: 7 serious events

Other events: 36 other events

Deaths: 0 deaths

Lubiprostone

Serious events: 7 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=214 participants at risk Placebo : 0 mcg capsules twice daily (BID)	Lubiprostone n=223 participants at risk Lubiprostone : 24 mcg capsules twice daily (BID)
Gastrointestinal disorders Irritable bowel syndrome	0.00% 0/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.45% 1/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.45% 1/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Gastrointestinal disorders Faecaloma	0.47% 1/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.00% 0/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Gastrointestinal disorders Abdominal pain upper	0.47% 1/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.00% 0/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Infections and infestations Pneumonia	0.00% 0/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.45% 1/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Infections and infestations Herpes zoster	0.00% 0/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.45% 1/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Infections and infestations Diverticulitis	0.47% 1/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.00% 0/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Nervous system disorders Multiple sclerosis relapse	0.00% 0/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.45% 1/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Nervous system disorders Migraine	0.00% 0/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.45% 1/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Cardiac disorders Tricuspid valve disease	0.47% 1/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.00% 0/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Cardiac disorders Angina pectoris	0.47% 1/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.00% 0/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Psychiatric disorders Confusional state	0.47% 1/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.00% 0/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Immune system disorders Hypersensitivity	0.47% 1/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.00% 0/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Hepatobiliary disorders Cholecystitis	0.00% 0/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.45% 1/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
General disorders Pyrexia	0.47% 1/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.00% 0/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
General disorders Malaise	0.47% 1/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.00% 0/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
General disorders Chills	0.47% 1/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	0.00% 0/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.

Other adverse events

Measure	Placebo n=214 participants at risk Placebo : 0 mcg capsules twice daily (BID)	Lubiprostone n=223 participants at risk Lubiprostone : 24 mcg capsules twice daily (BID)
Gastrointestinal disorders Nausea	8.9% 19/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	14.8% 33/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Gastrointestinal disorders Diarrhoea	4.2% 9/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	8.1% 18/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Gastrointestinal disorders Flatulence	4.2% 9/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	5.8% 13/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Gastrointestinal disorders Vomiting	3.3% 7/214 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.	5.4% 12/223 • Treatment-emergent adverse events (AEs): 13 weeks (from time of first dose to 7 days post-treatment) Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who randomzied and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.

Additional Information

VP, Clinical Development

Sucampo Pharma Americas, LLC

Phone: 301-961-3400

Email: info@sucampo.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60