Pharmacodynamic, Pharmacokinetic, and Tolerability Study of a Liquid Form of Lubiprostone in Adult Subjects With Chronic Idiopathic Constipation

Study Overview
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Brief Summary
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To evaluate the pharmacodynamics and tolerability of a liquid formulation of lubiprostone, as compared to matching placebo, when administered orally to subjects with chronic idiopathic constipation. Additionally, liquid formulation pharmacokinetics, including a comparison of fed and fasted pharmacokinetics, of the liquid formulation will be performed in a subset of subjects.

Official Title
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A Randomized, Placebo-controlled, Double-blinded, Multicenter Study of the Pharmacodynamics, Pharmacokinetics, and Tolerability of a Liquid Form of Lubiprostone in Adult Subjects With Chronic Idiopathic Constipation

Conditions
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Chronic Idiopathic Constipation

Intervention / Treatment
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* Drug: Lubiprostone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Medically-confirmed diagnosis of chronic idiopathic constipation Willing to discontinue use of prescribed or over-the-counter (OTC) medication that affects gastrointestinal motility during the study Stable dose of selective serotonin re-uptake inhibitors (SSRIs), serotonin-specific reuptake inhibitor (SNRIs), or monoamine oxidase inhibitors (MAO) inhibitors Exclusion Criteria: Any gastrointestinal (GI) condition, other than constipation, affecting GI motility or defecation. Medical/surgical condition that might interfere with the absorption, distribution, metabolism, or excretion of the study medication.

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lubiprostone<br> | Drug: Lubiprostone<br>* Liquid formulation, 12 mcg x 2 pumps administered orally twice daily (BID)<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching liquid placebo, 0 mcg x 2 pumps administered orally twice daily (BID)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Spontaneous Bowel Movements (SBMs) Within 1 Week | SBM is defined as any bowel movement (BM) that did not occur within the 24-hour period following use of a rescue medication. | within 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Consistency of SBMs at Week 1 | Stool consistency was rated according to the 7-point Bristol Stool Form Scale: Type 1 = separate hard lumps, like nuts (hard to pass), Type 2 = sausage-shaped but lumpy, Type 3 = like a sausage but with cracks on the surface, Type 4 = like a sausage or snake, smooth and soft, Type 5 = soft blobs with clear-cut edges (passed easily), Type 6 = fluffy pieces with ragged edges, a mushy stool, Type 7 = watery, no solid pieces; entirely liquid. | at Week 1 | 
| Overall Stool Consistency at Week 1 | Overall stool consistency was rated according to the 7-point Bristol Stool Form Scale: Type 1 = separate hard lumps, like nuts (hard to pass), Type 2 = sausage-shaped but lumpy, Type 3 = like a sausage but with cracks on the surface, Type 4 = like a sausage or snake, smooth and soft, Type 5 = soft blobs with clear-cut edges (passed easily), Type 6 = fluffy pieces with ragged edges, a mushy stool, Type 7 = watery, no solid pieces; entirely liquid. | at Week 1 | 
| Mean Change From Baseline in Stool Consistency at Week 1 | Stool consistency was rated according to the 7-point Bristol Stool Form Scale: Type 1 = separate hard lumps, like nuts (hard to pass), Type 2 = sausage-shaped but lumpy, Type 3 = like a sausage but with cracks on the surface, Type 4 = like a sausage or snake, smooth and soft, Type 5 = soft blobs with clear-cut edges (passed easily), Type 6 = fluffy pieces with ragged edges, a mushy stool, Type 7 = watery, no solid pieces; entirely liquid. The change from baseline was calculated as post-treatment value (mean) minus the baseline value (mean). | Baseline and Week 1 | 
| Overall Straining at Week 1 | Bowel straining was rated on a scale of 0 to 4 (0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe). | Week 1 | 
| Mean Change From Baseline in Straining at Week 1 | Bowel straining was rated as 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. The change from baseline was calculated as post-treatment value minus the baseline value. | Week 1 |