Trial Outcomes & Findings for Safety and Efficacy of Lubiprostone in Pediatric Patients With Constipation (NCT NCT00452335)

NCT ID: NCT00452335

Last Updated: 2019-12-17

Results Overview

Gathered as part of the daily electronic diary questions.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 127 participants
• Primary outcome timeframe: Week 1
• Results posted on: 2019-12-17

Participant Flow

127 participants were randomized to study treatment, however only 124 participants received study drug

Participant milestones

Measure	12 mcg QD Children (6-11 years of age) who are at least 12 kg, but less than 24 kg, body weight, and young children (\<6 years of age and able to swallow capsules) who are at least 12 kg body weight	12 mcg BID Up to 24 adolescents (12-17 years of age) and all children (6-11 years of age) who are at least 24 kg, but less than 36 kg, body weight	24 mcg BID Adolescents (12-17 years of age)and children (6-11 years of age) who are ≥36 kg body weight
Overall Study STARTED	27	65	32
Overall Study COMPLETED	25	61	23
Overall Study NOT COMPLETED	2	4	9

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy of Lubiprostone in Pediatric Patients With Constipation

Baseline characteristics by cohort

Measure	12 mcg QD n=27 Participants Children (6-11 years of age) who are at least 12 kg, but less than 24 kg, body weight, and young children (\<6 years of age and able to swallow capsules) who are at least 12 kg body weight	12 mcg BID n=65 Participants Up to 24 adolescents (12-17 years of age) and all children (6-11 years of age) who are at least 24 kg, but less than 36 kg, body weight	24 mcg BID n=32 Participants Adolescents (12-17 years of age)and children (6-11 years of age) who are ≥36 kg body weight	Total n=124 Participants Total of all reporting groups
Age, Categorical <=18 years	27 Participants n=5 Participants	65 Participants n=7 Participants	32 Participants n=5 Participants	124 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	5.5 years STANDARD_DEVIATION 1.67 • n=5 Participants	10.3 years STANDARD_DEVIATION 2.78 • n=7 Participants	13.9 years STANDARD_DEVIATION 3.00 • n=5 Participants	10.2 years STANDARD_DEVIATION 3.91 • n=4 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	24 Participants n=7 Participants	23 Participants n=5 Participants	59 Participants n=4 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	41 Participants n=7 Participants	9 Participants n=5 Participants	65 Participants n=4 Participants
Region of Enrollment United States	27 participants n=5 Participants	65 participants n=7 Participants	32 participants n=5 Participants	124 participants n=4 Participants

PRIMARY outcome

Timeframe: Week 1

Population: ITT population

Gathered as part of the daily electronic diary questions.

Outcome measures

Measure	12 mcg QD n=27 Participants Children (6-11 years of age) who are at least 12 kg, but less than 24 kg, body weight, and young children (\<6 years of age and able to swallow capsules) who are at least 12 kg body weight	12 mcg BID n=65 Participants Up to 24 adolescents (12-17 years of age) and all children (6-11 years of age) who are at least 24 kg, but less than 36 kg, body weight	24 mcg BID n=31 Participants Adolescents (12-17 years of age)and children (6-11 years of age) who are ≥36 kg body weight
Frequency of Spontaneous Bowel Movements	2.47 spontaneous bowel movements per week Standard Deviation 2.68	3.02 spontaneous bowel movements per week Standard Deviation 2.17	3.84 spontaneous bowel movements per week Standard Deviation 2.51

SECONDARY outcome

Timeframe: Weeks 2, 3, and 4

Population: ITT Population

Gathered as part of the daily electronic diary questions.

Outcome measures

Measure	12 mcg QD n=27 Participants Children (6-11 years of age) who are at least 12 kg, but less than 24 kg, body weight, and young children (\<6 years of age and able to swallow capsules) who are at least 12 kg body weight	12 mcg BID n=65 Participants Up to 24 adolescents (12-17 years of age) and all children (6-11 years of age) who are at least 24 kg, but less than 36 kg, body weight	24 mcg BID n=31 Participants Adolescents (12-17 years of age)and children (6-11 years of age) who are ≥36 kg body weight
Frequency of Spontaneous Bowel Movements Week 2	2.79 spontaneous bowel movements per week Standard Deviation 2.278	2.59 spontaneous bowel movements per week Standard Deviation 2.316	3.51 spontaneous bowel movements per week Standard Deviation 1.897
Frequency of Spontaneous Bowel Movements Week 3	2.64 spontaneous bowel movements per week Standard Deviation 2.210	2.60 spontaneous bowel movements per week Standard Deviation 2.006	3.58 spontaneous bowel movements per week Standard Deviation 2.422
Frequency of Spontaneous Bowel Movements Week 4	2.85 spontaneous bowel movements per week Standard Deviation 2.130	2.68 spontaneous bowel movements per week Standard Deviation 2.258	2.99 spontaneous bowel movements per week Standard Deviation 1.827

SECONDARY outcome

Timeframe: Weekly, up to 4 weeks

Population: ITT Population

As part of the daily diary, patients were asked to report the number of fecal incontinence episodes per day.

Outcome measures

Measure	12 mcg QD n=27 Participants Children (6-11 years of age) who are at least 12 kg, but less than 24 kg, body weight, and young children (\<6 years of age and able to swallow capsules) who are at least 12 kg body weight	12 mcg BID n=65 Participants Up to 24 adolescents (12-17 years of age) and all children (6-11 years of age) who are at least 24 kg, but less than 36 kg, body weight	24 mcg BID n=31 Participants Adolescents (12-17 years of age)and children (6-11 years of age) who are ≥36 kg body weight
Frequency of Fecal Incontinence Week 1	0.53 episodes of fecal incontinence per day Standard Deviation 1.141	0.22 episodes of fecal incontinence per day Standard Deviation 0.489	0.03 episodes of fecal incontinence per day Standard Deviation 0.089
Frequency of Fecal Incontinence Week 2	0.37 episodes of fecal incontinence per day Standard Deviation 0.768	0.21 episodes of fecal incontinence per day Standard Deviation 0.446	0.05 episodes of fecal incontinence per day Standard Deviation 0.148
Frequency of Fecal Incontinence Week 3	0.40 episodes of fecal incontinence per day Standard Deviation 0.989	0.16 episodes of fecal incontinence per day Standard Deviation 0.336	0.01 episodes of fecal incontinence per day Standard Deviation 0.060
Frequency of Fecal Incontinence Week 4	0.48 episodes of fecal incontinence per day Standard Deviation 1.168	0.17 episodes of fecal incontinence per day Standard Deviation 0.457	0.02 episodes of fecal incontinence per day Standard Deviation 0.074

SECONDARY outcome

Timeframe: Weekly, up to 4 weeks

Population: ITT Population

Bowel straining assessed based on the following scale: 0 = no straining, 1 = mild straining, 2 = moderate straining, 3 = severe straining, and 4 = very severe straining.

Outcome measures

Measure	12 mcg QD n=27 Participants Children (6-11 years of age) who are at least 12 kg, but less than 24 kg, body weight, and young children (\<6 years of age and able to swallow capsules) who are at least 12 kg body weight	12 mcg BID n=65 Participants Up to 24 adolescents (12-17 years of age) and all children (6-11 years of age) who are at least 24 kg, but less than 36 kg, body weight	24 mcg BID n=31 Participants Adolescents (12-17 years of age)and children (6-11 years of age) who are ≥36 kg body weight
Straining Associated With SBMs Week 1	1.70 units on a scale Standard Deviation 1.074	1.34 units on a scale Standard Deviation 1.001	1.44 units on a scale Standard Deviation 0.890
Straining Associated With SBMs Week 2	1.02 units on a scale Standard Deviation 1.010	1.22 units on a scale Standard Deviation 0.868	1.30 units on a scale Standard Deviation 1.003
Straining Associated With SBMs Week 3	1.11 units on a scale Standard Deviation 0.857	1.11 units on a scale Standard Deviation 0.809	1.16 units on a scale Standard Deviation 1.130
Straining Associated With SBMs Week 4	1.03 units on a scale Standard Deviation 0.887	1.31 units on a scale Standard Deviation 1.096	0.97 units on a scale Standard Deviation 1.089

SECONDARY outcome

Timeframe: Weekly, up to 4 weeks

Population: ITT Population

Stool consistency was captured using the Bristol Stool Form Scale: 1 = Separate hard lumps like nuts, 2 = Sausage shaped but lumpy, 3 = Like a sausage but with cracks on surface, 4 = Like a sausage or snake, smooth and soft, 5 = Soft blobs with clear-cut edges, 6 = Fluffy pieces with ragged edges, a mushy stool, and 7 = Watery, no solid pieces.

Outcome measures

Measure	12 mcg QD n=27 Participants Children (6-11 years of age) who are at least 12 kg, but less than 24 kg, body weight, and young children (\<6 years of age and able to swallow capsules) who are at least 12 kg body weight	12 mcg BID n=65 Participants Up to 24 adolescents (12-17 years of age) and all children (6-11 years of age) who are at least 24 kg, but less than 36 kg, body weight	24 mcg BID n=31 Participants Adolescents (12-17 years of age)and children (6-11 years of age) who are ≥36 kg body weight
Stool Consistency of SBMs Week 1	2.87 units on a scale Standard Deviation 1.197	3.20 units on a scale Standard Deviation 1.168	3.14 units on a scale Standard Deviation 1.249
Stool Consistency of SBMs Week 2	3.09 units on a scale Standard Deviation 1.078	2.90 units on a scale Standard Deviation 1.198	3.22 units on a scale Standard Deviation 1.394
Stool Consistency of SBMs Week 3	2.93 units on a scale Standard Deviation 0.796	3.31 units on a scale Standard Deviation 1.121	3.59 units on a scale Standard Deviation 1.168
Stool Consistency of SBMs Week 4	3.20 units on a scale Standard Deviation 0.904	2.96 units on a scale Standard Deviation 1.160	4.01 units on a scale Standard Deviation 1.631

SECONDARY outcome

Timeframe: Weekly, up to 4 weeks

Population: ITT Population

Abdominal bloating was assessed based on the following scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe.

Outcome measures

Measure	12 mcg QD n=27 Participants Children (6-11 years of age) who are at least 12 kg, but less than 24 kg, body weight, and young children (\<6 years of age and able to swallow capsules) who are at least 12 kg body weight	12 mcg BID n=65 Participants Up to 24 adolescents (12-17 years of age) and all children (6-11 years of age) who are at least 24 kg, but less than 36 kg, body weight	24 mcg BID n=31 Participants Adolescents (12-17 years of age)and children (6-11 years of age) who are ≥36 kg body weight
Abdominal Bloating Week 1	1.16 units on a scale Standard Deviation 0.800	1.39 units on a scale Standard Deviation 1.150	1.79 units on a scale Standard Deviation 0.876
Abdominal Bloating Week 2	1.08 units on a scale Standard Deviation 0.929	1.12 units on a scale Standard Deviation 1.027	1.16 units on a scale Standard Deviation 0.987
Abdominal Bloating Week 3	0.82 units on a scale Standard Deviation 1.006	1.00 units on a scale Standard Deviation 0.937	1.08 units on a scale Standard Deviation 1.018
Abdominal Bloating Week 4	0.96 units on a scale Standard Deviation 1.065	1.04 units on a scale Standard Deviation 0.865	1.05 units on a scale Standard Deviation 0.950

SECONDARY outcome

Timeframe: Weekly, up to 4 weeks

Population: ITT Population

Abdominal discomfort was assessed based on the following scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe.

Outcome measures

Measure	12 mcg QD n=27 Participants Children (6-11 years of age) who are at least 12 kg, but less than 24 kg, body weight, and young children (\<6 years of age and able to swallow capsules) who are at least 12 kg body weight	12 mcg BID n=65 Participants Up to 24 adolescents (12-17 years of age) and all children (6-11 years of age) who are at least 24 kg, but less than 36 kg, body weight	24 mcg BID n=31 Participants Adolescents (12-17 years of age)and children (6-11 years of age) who are ≥36 kg body weight
Abdominal Discomfort Week 1	0.84 units on a scale Standard Deviation 0.800	1.16 units on a scale Standard Deviation 1.134	1.43 units on a scale Standard Deviation 1.289
Abdominal Discomfort Week 2	1.08 units on a scale Standard Deviation 0.929	0.93 units on a scale Standard Deviation 0.918	1.20 units on a scale Standard Deviation 1.080
Abdominal Discomfort Week 3	0.82 units on a scale Standard Deviation 0.795	0.90 units on a scale Standard Deviation 0.892	1.17 units on a scale Standard Deviation 1.204
Abdominal Discomfort Week 4	0.87 units on a scale Standard Deviation 0.869	1.05 units on a scale Standard Deviation 0.915	1.14 units on a scale Standard Deviation 1.125

SECONDARY outcome

Timeframe: Weekly, up to 4 weeks

Population: ITT Population

Pain associated with SBMs was assessed based on the following scale: 0 = no pain, 1 = mild pain, 2 = moderate pain, 3 = severe pain, and 4 = very severe pain.

Outcome measures

Measure	12 mcg QD n=27 Participants Children (6-11 years of age) who are at least 12 kg, but less than 24 kg, body weight, and young children (\<6 years of age and able to swallow capsules) who are at least 12 kg body weight	12 mcg BID n=65 Participants Up to 24 adolescents (12-17 years of age) and all children (6-11 years of age) who are at least 24 kg, but less than 36 kg, body weight	24 mcg BID n=31 Participants Adolescents (12-17 years of age)and children (6-11 years of age) who are ≥36 kg body weight
Pain Associated With SBMs Week 1	1.56 units on a scale Standard Deviation 1.051	1.13 units on a scale Standard Deviation 0.970	1.14 units on a scale Standard Deviation 0.873
Pain Associated With SBMs Week 2	0.72 units on a scale Standard Deviation 1.009	1.06 units on a scale Standard Deviation 0.758	1.10 units on a scale Standard Deviation 1.073
Pain Associated With SBMs Week 3	0.88 units on a scale Standard Deviation 0.929	0.91 units on a scale Standard Deviation 0.915	1.01 units on a scale Standard Deviation 1.089
Pain Associated With SBMs Week 4	0.82 units on a scale Standard Deviation 0.978	1.07 units on a scale Standard Deviation 1.047	1.07 units on a scale Standard Deviation 1.298

SECONDARY outcome

Timeframe: Weekly, up to 4 weeks

Population: ITT Population

Constipation severity was assessed based on the following scale 0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe.

Outcome measures

Measure	12 mcg QD n=27 Participants Children (6-11 years of age) who are at least 12 kg, but less than 24 kg, body weight, and young children (\<6 years of age and able to swallow capsules) who are at least 12 kg body weight	12 mcg BID n=65 Participants Up to 24 adolescents (12-17 years of age) and all children (6-11 years of age) who are at least 24 kg, but less than 36 kg, body weight	24 mcg BID n=31 Participants Adolescents (12-17 years of age)and children (6-11 years of age) who are ≥36 kg body weight
Constipation Severity Week 1	1.92 units on a scale Standard Deviation 1.038	1.69 units on a scale Standard Deviation 0.951	1.79 units on a scale Standard Deviation 0.917
Constipation Severity Week 2	1.46 units on a scale Standard Deviation 0.977	1.43 units on a scale Standard Deviation 0.945	1.40 units on a scale Standard Deviation 0.816
Constipation Severity Week 3	1.59 units on a scale Standard Deviation 0.908	1.36 units on a scale Standard Deviation 1.055	1.38 units on a scale Standard Deviation 0.875
Constipation Severity Week 4	1.43 units on a scale Standard Deviation 1.121	1.28 units on a scale Standard Deviation 1.031	1.59 units on a scale Standard Deviation 1.054

SECONDARY outcome

Timeframe: Weekly, up to 4 weeks

Population: ITT Population

Treatment effectiveness was assessed with the following scale: 0 = not at all effective, 1 = a little bit effective, 2 = moderately effective, 3 = quite a bit effective, and 4 = extremely effective.

Outcome measures

Measure	12 mcg QD n=27 Participants Children (6-11 years of age) who are at least 12 kg, but less than 24 kg, body weight, and young children (\<6 years of age and able to swallow capsules) who are at least 12 kg body weight	12 mcg BID n=65 Participants Up to 24 adolescents (12-17 years of age) and all children (6-11 years of age) who are at least 24 kg, but less than 36 kg, body weight	24 mcg BID n=31 Participants Adolescents (12-17 years of age)and children (6-11 years of age) who are ≥36 kg body weight
Treatment Effectiveness Week 1	1.2 units on a scale Standard Deviation 1.30	1.6 units on a scale Standard Deviation 1.27	1.7 units on a scale Standard Deviation 0.86
Treatment Effectiveness Week 2	1.6 units on a scale Standard Deviation 1.28	1.7 units on a scale Standard Deviation 1.24	2.0 units on a scale Standard Deviation 1.17
Treatment Effectiveness Week 3	1.9 units on a scale Standard Deviation 1.51	1.8 units on a scale Standard Deviation 1.31	1.8 units on a scale Standard Deviation 1.24
Treatment Effectiveness Week 4	2.0 units on a scale Standard Deviation 1.43	1.8 units on a scale Standard Deviation 1.22	1.9 units on a scale Standard Deviation 1.10

Adverse Events

12 mcg QD

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

12 mcg BID

Serious events: 1 serious events

Other events: 23 other events

Deaths: 0 deaths

24 mcg BID

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Measure	12 mcg QD n=27 participants at risk Children (6-11 years of age) who are at least 12 kg, but less than 24 kg, body weight, and young children (\<6 years of age and able to swallow capsules) who are at least 12 kg body weight	12 mcg BID n=65 participants at risk Up to 24 adolescents (12-17 years of age) and all children (6-11 years of age) who are at least 24 kg, but less than 36 kg, body weight	24 mcg BID n=32 participants at risk Adolescents (12-17 years of age)and children (6-11 years of age) who are ≥36 kg body weight
Gastrointestinal disorders Abdominal pain	0.00% 0/27 • Treatment-emergent AEs: up to 4 weeks plus 7 days (from time of first dose to 7 days post-treatment)	1.5% 1/65 • Treatment-emergent AEs: up to 4 weeks plus 7 days (from time of first dose to 7 days post-treatment)	0.00% 0/32 • Treatment-emergent AEs: up to 4 weeks plus 7 days (from time of first dose to 7 days post-treatment)

Other adverse events

Measure	12 mcg QD n=27 participants at risk Children (6-11 years of age) who are at least 12 kg, but less than 24 kg, body weight, and young children (\<6 years of age and able to swallow capsules) who are at least 12 kg body weight	12 mcg BID n=65 participants at risk Up to 24 adolescents (12-17 years of age) and all children (6-11 years of age) who are at least 24 kg, but less than 36 kg, body weight	24 mcg BID n=32 participants at risk Adolescents (12-17 years of age)and children (6-11 years of age) who are ≥36 kg body weight
Gastrointestinal disorders Abdominal pain	7.4% 2/27 • Treatment-emergent AEs: up to 4 weeks plus 7 days (from time of first dose to 7 days post-treatment)	6.2% 4/65 • Treatment-emergent AEs: up to 4 weeks plus 7 days (from time of first dose to 7 days post-treatment)	9.4% 3/32 • Treatment-emergent AEs: up to 4 weeks plus 7 days (from time of first dose to 7 days post-treatment)
Gastrointestinal disorders Diarrhoea	11.1% 3/27 • Treatment-emergent AEs: up to 4 weeks plus 7 days (from time of first dose to 7 days post-treatment)	6.2% 4/65 • Treatment-emergent AEs: up to 4 weeks plus 7 days (from time of first dose to 7 days post-treatment)	9.4% 3/32 • Treatment-emergent AEs: up to 4 weeks plus 7 days (from time of first dose to 7 days post-treatment)
Gastrointestinal disorders Nausea	3.7% 1/27 • Treatment-emergent AEs: up to 4 weeks plus 7 days (from time of first dose to 7 days post-treatment)	18.5% 12/65 • Treatment-emergent AEs: up to 4 weeks plus 7 days (from time of first dose to 7 days post-treatment)	31.2% 10/32 • Treatment-emergent AEs: up to 4 weeks plus 7 days (from time of first dose to 7 days post-treatment)
Gastrointestinal disorders Vomiting	14.8% 4/27 • Treatment-emergent AEs: up to 4 weeks plus 7 days (from time of first dose to 7 days post-treatment)	9.2% 6/65 • Treatment-emergent AEs: up to 4 weeks plus 7 days (from time of first dose to 7 days post-treatment)	15.6% 5/32 • Treatment-emergent AEs: up to 4 weeks plus 7 days (from time of first dose to 7 days post-treatment)
Nervous system disorders Headache	0.00% 0/27 • Treatment-emergent AEs: up to 4 weeks plus 7 days (from time of first dose to 7 days post-treatment)	6.2% 4/65 • Treatment-emergent AEs: up to 4 weeks plus 7 days (from time of first dose to 7 days post-treatment)	9.4% 3/32 • Treatment-emergent AEs: up to 4 weeks plus 7 days (from time of first dose to 7 days post-treatment)

Additional Information

VP, Clinical Development

Sucampo Pharma Americas, Inc.

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