Safety and Efficacy of Lubiprostone in Pediatric Patients With Constipation

Study Overview
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Brief Summary
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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.

Official Title
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A Multi-center, Open-labeled Study of the Safety, Efficacy, and Pharmacokinetics of Lubiprostone in Pediatric Patients With Constipation

Conditions
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Constipation

Intervention / Treatment
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* Drug: Lubiprostone
* Drug: Lubiprostone
* Drug: Lubiprostone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lubiprostone 12 mcg QD<br>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 | Drug: Lubiprostone<br>* 12 mcg capsule once daily (QD)<br>* Other names: Amitiza®;|
| Experimental: Lubiprostone 12 mcg BID<br>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 | Drug: Lubiprostone<br>* 12 mcg capsule twice daily (BID)<br>* Other names: Amitiza®;|
| Experimental: Lubiprostone 24 mcg BID<br>Adolescents (12-17 years of age)and children (6-11 years of age) who are ≥36 kg body weight | Drug: Lubiprostone<br>* 24 mcg capsule twice daily (BID)<br>* Other names: Amitiza®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Spontaneous Bowel Movements | Gathered as part of the daily electronic diary questions. | Week 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Spontaneous Bowel Movements | Gathered as part of the daily electronic diary questions. | Weeks 2, 3, and 4 | 
| Frequency of Fecal Incontinence | As part of the daily diary, patients were asked to report the number of fecal incontinence episodes per day. | Weekly, up to 4 weeks | 
| 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. | Weekly, up to 4 weeks | 
| 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. | Weekly, up to 4 weeks | 
| Abdominal Bloating | Abdominal bloating was assessed based on the following scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe. | Weekly, up to 4 weeks | 
| Abdominal Discomfort | Abdominal discomfort was assessed based on the following scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe. | Weekly, up to 4 weeks | 
| 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. | Weekly, up to 4 weeks | 
| Constipation Severity | Constipation severity was assessed based on the following scale 0 = absent, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe. | Weekly, up to 4 weeks | 
| 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. | Weekly, up to 4 weeks |