Constipation
Conditions
Brief summary
The primary purpose of this study is to evaluate the safety and efficacy of lubiprostone in a pediatric population with constipation, including the pharmacokinetics of lubiprostone, in a subset of patients.
Interventions
DRUGLubiprostone
12 mcg capsule once daily (QD)
Sponsors
Sucampo Pharmaceuticals, Inc.
Sucampo Pharma Americas, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Less than 18 years of age * Weight of at least 12 kg and capable of swallowing a capsule * Able to refrain from use of medications known to treat or associated with constipation symptoms * Stable fiber therapy or ADHD therapy if using such medications * Patient/Caregiver able to complete daily diary * Patient able to use recommended rectal and/or oral rescue medications if needed
Exclusion criteria
* Constipation is associated with some medical, anatomic, physical, organic, or other condition * Hirschsprung's Disease or Nonretentive Fecal Incontinence * Untreated fecal impactions or impactions requiring digital manipulation * Open gastrointestinal/abdominal surgery or laparoscopic surgery at the investigator discretion * Organic bowel disorder, mechanical bowel obstruction, pseudo-obstruction, or unexplained weight loss * Uncontrolled cardiovascular, liver or lung disease, neurologic or psychiatric disorder, other systemic disease, or abnormal laboratory tests at the investigator discretion * If female, is currently pregnant or nursing, or plans to become pregnant or nurse during the clinical study * Sexually active males and females must utilize acceptable birth control methods * Prior use of lubiprostone, Amitiza, SPI-0211, or RU-0211
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Spontaneous Bowel Movements | Week 1 | Gathered as part of the daily electronic diary questions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Fecal Incontinence | Weekly, up to 4 weeks | As part of the daily diary, patients were asked to report the number of fecal incontinence episodes per day. |
| Straining Associated With SBMs | Weekly, up to 4 weeks | 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. |
| Stool Consistency of SBMs | Weekly, up to 4 weeks | 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. |
| Abdominal Bloating | Weekly, up to 4 weeks | Abdominal bloating was assessed based on the following scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe. |
| Frequency of Spontaneous Bowel Movements | Weeks 2, 3, and 4 | Gathered as part of the daily electronic diary questions. |
| Pain Associated With SBMs | Weekly, up to 4 weeks | 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. |
| Constipation Severity | Weekly, up to 4 weeks | Constipation severity was assessed based on the following scale 0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe. |
| Treatment Effectiveness | Weekly, up to 4 weeks | 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. |
| Abdominal Discomfort | Weekly, up to 4 weeks | Abdominal discomfort was assessed based on the following scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe. |
Countries
United States
Participant flow
Pre-assignment details
127 participants were randomized to study treatment, however only 124 participants received study drug
Participants by arm
| Arm | Count |
|---|---|
| 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 | 27 |
| 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 | 65 |
| 24 mcg BID Adolescents (12-17 years of age)and children (6-11 years of age) who are ≥36 kg body weight | 32 |
| Total | 124 |
Baseline characteristics
| Characteristic | 12 mcg BID | 24 mcg BID | 12 mcg QD | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 65 Participants | 32 Participants | 27 Participants | 124 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 10.3 years STANDARD_DEVIATION 2.78 | 13.9 years STANDARD_DEVIATION 3 | 5.5 years STANDARD_DEVIATION 1.67 | 10.2 years STANDARD_DEVIATION 3.91 |
| Region of Enrollment United States | 65 participants | 32 participants | 27 participants | 124 participants |
| Sex: Female, Male Female | 24 Participants | 23 Participants | 12 Participants | 59 Participants |
| Sex: Female, Male Male | 41 Participants | 9 Participants | 15 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 27 | 23 / 65 | 14 / 32 |
| serious Total, serious adverse events | 0 / 27 | 1 / 65 | 0 / 32 |
Outcome results
Primary
Frequency of Spontaneous Bowel Movements
Gathered as part of the daily electronic diary questions.
Time frame: Week 1
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 12 mcg QD | Frequency of Spontaneous Bowel Movements | 2.47 spontaneous bowel movements per week | Standard Deviation 2.68 |
| 12 mcg BID | Frequency of Spontaneous Bowel Movements | 3.02 spontaneous bowel movements per week | Standard Deviation 2.17 |
| 24 mcg BID | Frequency of Spontaneous Bowel Movements | 3.84 spontaneous bowel movements per week | Standard Deviation 2.51 |
Secondary
Abdominal Bloating
Abdominal bloating was assessed based on the following scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe.
Time frame: Weekly, up to 4 weeks
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 12 mcg QD | Abdominal Bloating | Week 1 | 1.16 units on a scale | Standard Deviation 0.8 |
| 12 mcg QD | Abdominal Bloating | Week 2 | 1.08 units on a scale | Standard Deviation 0.929 |
| 12 mcg QD | Abdominal Bloating | Week 3 | 0.82 units on a scale | Standard Deviation 1.006 |
| 12 mcg QD | Abdominal Bloating | Week 4 | 0.96 units on a scale | Standard Deviation 1.065 |
| 12 mcg BID | Abdominal Bloating | Week 4 | 1.04 units on a scale | Standard Deviation 0.865 |
| 12 mcg BID | Abdominal Bloating | Week 1 | 1.39 units on a scale | Standard Deviation 1.15 |
| 12 mcg BID | Abdominal Bloating | Week 3 | 1.00 units on a scale | Standard Deviation 0.937 |
| 12 mcg BID | Abdominal Bloating | Week 2 | 1.12 units on a scale | Standard Deviation 1.027 |
| 24 mcg BID | Abdominal Bloating | Week 4 | 1.05 units on a scale | Standard Deviation 0.95 |
| 24 mcg BID | Abdominal Bloating | Week 2 | 1.16 units on a scale | Standard Deviation 0.987 |
| 24 mcg BID | Abdominal Bloating | Week 3 | 1.08 units on a scale | Standard Deviation 1.018 |
| 24 mcg BID | Abdominal Bloating | Week 1 | 1.79 units on a scale | Standard Deviation 0.876 |
Secondary
Abdominal Discomfort
Abdominal discomfort was assessed based on the following scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe.
Time frame: Weekly, up to 4 weeks
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 12 mcg QD | Abdominal Discomfort | Week 3 | 0.82 units on a scale | Standard Deviation 0.795 |
| 12 mcg QD | Abdominal Discomfort | Week 2 | 1.08 units on a scale | Standard Deviation 0.929 |
| 12 mcg QD | Abdominal Discomfort | Week 1 | 0.84 units on a scale | Standard Deviation 0.8 |
| 12 mcg QD | Abdominal Discomfort | Week 4 | 0.87 units on a scale | Standard Deviation 0.869 |
| 12 mcg BID | Abdominal Discomfort | Week 3 | 0.90 units on a scale | Standard Deviation 0.892 |
| 12 mcg BID | Abdominal Discomfort | Week 1 | 1.16 units on a scale | Standard Deviation 1.134 |
| 12 mcg BID | Abdominal Discomfort | Week 2 | 0.93 units on a scale | Standard Deviation 0.918 |
| 12 mcg BID | Abdominal Discomfort | Week 4 | 1.05 units on a scale | Standard Deviation 0.915 |
| 24 mcg BID | Abdominal Discomfort | Week 1 | 1.43 units on a scale | Standard Deviation 1.289 |
| 24 mcg BID | Abdominal Discomfort | Week 3 | 1.17 units on a scale | Standard Deviation 1.204 |
| 24 mcg BID | Abdominal Discomfort | Week 4 | 1.14 units on a scale | Standard Deviation 1.125 |
| 24 mcg BID | Abdominal Discomfort | Week 2 | 1.20 units on a scale | Standard Deviation 1.08 |
Secondary
Constipation Severity
Constipation severity was assessed based on the following scale 0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe.
Time frame: Weekly, up to 4 weeks
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 12 mcg QD | Constipation Severity | Week 1 | 1.92 units on a scale | Standard Deviation 1.038 |
| 12 mcg QD | Constipation Severity | Week 2 | 1.46 units on a scale | Standard Deviation 0.977 |
| 12 mcg QD | Constipation Severity | Week 3 | 1.59 units on a scale | Standard Deviation 0.908 |
| 12 mcg QD | Constipation Severity | Week 4 | 1.43 units on a scale | Standard Deviation 1.121 |
| 12 mcg BID | Constipation Severity | Week 4 | 1.28 units on a scale | Standard Deviation 1.031 |
| 12 mcg BID | Constipation Severity | Week 1 | 1.69 units on a scale | Standard Deviation 0.951 |
| 12 mcg BID | Constipation Severity | Week 3 | 1.36 units on a scale | Standard Deviation 1.055 |
| 12 mcg BID | Constipation Severity | Week 2 | 1.43 units on a scale | Standard Deviation 0.945 |
| 24 mcg BID | Constipation Severity | Week 4 | 1.59 units on a scale | Standard Deviation 1.054 |
| 24 mcg BID | Constipation Severity | Week 2 | 1.40 units on a scale | Standard Deviation 0.816 |
| 24 mcg BID | Constipation Severity | Week 3 | 1.38 units on a scale | Standard Deviation 0.875 |
| 24 mcg BID | Constipation Severity | Week 1 | 1.79 units on a scale | Standard Deviation 0.917 |
Secondary
Frequency of Fecal Incontinence
As part of the daily diary, patients were asked to report the number of fecal incontinence episodes per day.
Time frame: Weekly, up to 4 weeks
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 12 mcg QD | Frequency of Fecal Incontinence | Week 1 | 0.53 episodes of fecal incontinence per day | Standard Deviation 1.141 |
| 12 mcg QD | Frequency of Fecal Incontinence | Week 2 | 0.37 episodes of fecal incontinence per day | Standard Deviation 0.768 |
| 12 mcg QD | Frequency of Fecal Incontinence | Week 3 | 0.40 episodes of fecal incontinence per day | Standard Deviation 0.989 |
| 12 mcg QD | Frequency of Fecal Incontinence | Week 4 | 0.48 episodes of fecal incontinence per day | Standard Deviation 1.168 |
| 12 mcg BID | Frequency of Fecal Incontinence | Week 4 | 0.17 episodes of fecal incontinence per day | Standard Deviation 0.457 |
| 12 mcg BID | Frequency of Fecal Incontinence | Week 1 | 0.22 episodes of fecal incontinence per day | Standard Deviation 0.489 |
| 12 mcg BID | Frequency of Fecal Incontinence | Week 3 | 0.16 episodes of fecal incontinence per day | Standard Deviation 0.336 |
| 12 mcg BID | Frequency of Fecal Incontinence | Week 2 | 0.21 episodes of fecal incontinence per day | Standard Deviation 0.446 |
| 24 mcg BID | Frequency of Fecal Incontinence | Week 4 | 0.02 episodes of fecal incontinence per day | Standard Deviation 0.074 |
| 24 mcg BID | Frequency of Fecal Incontinence | Week 2 | 0.05 episodes of fecal incontinence per day | Standard Deviation 0.148 |
| 24 mcg BID | Frequency of Fecal Incontinence | Week 3 | 0.01 episodes of fecal incontinence per day | Standard Deviation 0.06 |
| 24 mcg BID | Frequency of Fecal Incontinence | Week 1 | 0.03 episodes of fecal incontinence per day | Standard Deviation 0.089 |
Secondary
Frequency of Spontaneous Bowel Movements
Gathered as part of the daily electronic diary questions.
Time frame: Weeks 2, 3, and 4
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 12 mcg QD | Frequency of Spontaneous Bowel Movements | Week 3 | 2.64 spontaneous bowel movements per week | Standard Deviation 2.21 |
| 12 mcg QD | Frequency of Spontaneous Bowel Movements | Week 2 | 2.79 spontaneous bowel movements per week | Standard Deviation 2.278 |
| 12 mcg QD | Frequency of Spontaneous Bowel Movements | Week 4 | 2.85 spontaneous bowel movements per week | Standard Deviation 2.13 |
| 12 mcg BID | Frequency of Spontaneous Bowel Movements | Week 3 | 2.60 spontaneous bowel movements per week | Standard Deviation 2.006 |
| 12 mcg BID | Frequency of Spontaneous Bowel Movements | Week 2 | 2.59 spontaneous bowel movements per week | Standard Deviation 2.316 |
| 12 mcg BID | Frequency of Spontaneous Bowel Movements | Week 4 | 2.68 spontaneous bowel movements per week | Standard Deviation 2.258 |
| 24 mcg BID | Frequency of Spontaneous Bowel Movements | Week 2 | 3.51 spontaneous bowel movements per week | Standard Deviation 1.897 |
| 24 mcg BID | Frequency of Spontaneous Bowel Movements | Week 4 | 2.99 spontaneous bowel movements per week | Standard Deviation 1.827 |
| 24 mcg BID | Frequency of Spontaneous Bowel Movements | Week 3 | 3.58 spontaneous bowel movements per week | Standard Deviation 2.422 |
Secondary
Pain Associated With SBMs
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.
Time frame: Weekly, up to 4 weeks
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 12 mcg QD | Pain Associated With SBMs | Week 1 | 1.56 units on a scale | Standard Deviation 1.051 |
| 12 mcg QD | Pain Associated With SBMs | Week 2 | 0.72 units on a scale | Standard Deviation 1.009 |
| 12 mcg QD | Pain Associated With SBMs | Week 3 | 0.88 units on a scale | Standard Deviation 0.929 |
| 12 mcg QD | Pain Associated With SBMs | Week 4 | 0.82 units on a scale | Standard Deviation 0.978 |
| 12 mcg BID | Pain Associated With SBMs | Week 4 | 1.07 units on a scale | Standard Deviation 1.047 |
| 12 mcg BID | Pain Associated With SBMs | Week 1 | 1.13 units on a scale | Standard Deviation 0.97 |
| 12 mcg BID | Pain Associated With SBMs | Week 3 | 0.91 units on a scale | Standard Deviation 0.915 |
| 12 mcg BID | Pain Associated With SBMs | Week 2 | 1.06 units on a scale | Standard Deviation 0.758 |
| 24 mcg BID | Pain Associated With SBMs | Week 4 | 1.07 units on a scale | Standard Deviation 1.298 |
| 24 mcg BID | Pain Associated With SBMs | Week 2 | 1.10 units on a scale | Standard Deviation 1.073 |
| 24 mcg BID | Pain Associated With SBMs | Week 3 | 1.01 units on a scale | Standard Deviation 1.089 |
| 24 mcg BID | Pain Associated With SBMs | Week 1 | 1.14 units on a scale | Standard Deviation 0.873 |
Secondary
Stool Consistency of SBMs
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.
Time frame: Weekly, up to 4 weeks
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 12 mcg QD | Stool Consistency of SBMs | Week 1 | 2.87 units on a scale | Standard Deviation 1.197 |
| 12 mcg QD | Stool Consistency of SBMs | Week 2 | 3.09 units on a scale | Standard Deviation 1.078 |
| 12 mcg QD | Stool Consistency of SBMs | Week 3 | 2.93 units on a scale | Standard Deviation 0.796 |
| 12 mcg QD | Stool Consistency of SBMs | Week 4 | 3.20 units on a scale | Standard Deviation 0.904 |
| 12 mcg BID | Stool Consistency of SBMs | Week 4 | 2.96 units on a scale | Standard Deviation 1.16 |
| 12 mcg BID | Stool Consistency of SBMs | Week 1 | 3.20 units on a scale | Standard Deviation 1.168 |
| 12 mcg BID | Stool Consistency of SBMs | Week 3 | 3.31 units on a scale | Standard Deviation 1.121 |
| 12 mcg BID | Stool Consistency of SBMs | Week 2 | 2.90 units on a scale | Standard Deviation 1.198 |
| 24 mcg BID | Stool Consistency of SBMs | Week 4 | 4.01 units on a scale | Standard Deviation 1.631 |
| 24 mcg BID | Stool Consistency of SBMs | Week 2 | 3.22 units on a scale | Standard Deviation 1.394 |
| 24 mcg BID | Stool Consistency of SBMs | Week 3 | 3.59 units on a scale | Standard Deviation 1.168 |
| 24 mcg BID | Stool Consistency of SBMs | Week 1 | 3.14 units on a scale | Standard Deviation 1.249 |
Secondary
Straining Associated With SBMs
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.
Time frame: Weekly, up to 4 weeks
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 12 mcg QD | Straining Associated With SBMs | Week 3 | 1.11 units on a scale | Standard Deviation 0.857 |
| 12 mcg QD | Straining Associated With SBMs | Week 1 | 1.70 units on a scale | Standard Deviation 1.074 |
| 12 mcg QD | Straining Associated With SBMs | Week 4 | 1.03 units on a scale | Standard Deviation 0.887 |
| 12 mcg QD | Straining Associated With SBMs | Week 2 | 1.02 units on a scale | Standard Deviation 1.01 |
| 12 mcg BID | Straining Associated With SBMs | Week 3 | 1.11 units on a scale | Standard Deviation 0.809 |
| 12 mcg BID | Straining Associated With SBMs | Week 2 | 1.22 units on a scale | Standard Deviation 0.868 |
| 12 mcg BID | Straining Associated With SBMs | Week 1 | 1.34 units on a scale | Standard Deviation 1.001 |
| 12 mcg BID | Straining Associated With SBMs | Week 4 | 1.31 units on a scale | Standard Deviation 1.096 |
| 24 mcg BID | Straining Associated With SBMs | Week 4 | 0.97 units on a scale | Standard Deviation 1.089 |
| 24 mcg BID | Straining Associated With SBMs | Week 1 | 1.44 units on a scale | Standard Deviation 0.89 |
| 24 mcg BID | Straining Associated With SBMs | Week 2 | 1.30 units on a scale | Standard Deviation 1.003 |
| 24 mcg BID | Straining Associated With SBMs | Week 3 | 1.16 units on a scale | Standard Deviation 1.13 |
Secondary
Treatment Effectiveness
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.
Time frame: Weekly, up to 4 weeks
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 12 mcg QD | Treatment Effectiveness | Week 4 | 2.0 units on a scale | Standard Deviation 1.43 |
| 12 mcg QD | Treatment Effectiveness | Week 3 | 1.9 units on a scale | Standard Deviation 1.51 |
| 12 mcg QD | Treatment Effectiveness | Week 2 | 1.6 units on a scale | Standard Deviation 1.28 |
| 12 mcg QD | Treatment Effectiveness | Week 1 | 1.2 units on a scale | Standard Deviation 1.3 |
| 12 mcg BID | Treatment Effectiveness | Week 1 | 1.6 units on a scale | Standard Deviation 1.27 |
| 12 mcg BID | Treatment Effectiveness | Week 2 | 1.7 units on a scale | Standard Deviation 1.24 |
| 12 mcg BID | Treatment Effectiveness | Week 3 | 1.8 units on a scale | Standard Deviation 1.31 |
| 12 mcg BID | Treatment Effectiveness | Week 4 | 1.8 units on a scale | Standard Deviation 1.22 |
| 24 mcg BID | Treatment Effectiveness | Week 3 | 1.8 units on a scale | Standard Deviation 1.24 |
| 24 mcg BID | Treatment Effectiveness | Week 1 | 1.7 units on a scale | Standard Deviation 0.86 |
| 24 mcg BID | Treatment Effectiveness | Week 2 | 2.0 units on a scale | Standard Deviation 1.17 |
| 24 mcg BID | Treatment Effectiveness | Week 4 | 1.9 units on a scale | Standard Deviation 1.1 |