Chronic Idiopathic Constipation
Conditions
Brief summary
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.
Interventions
DRUGLubiprostone
Liquid formulation, 12 mcg x 2 pumps administered orally twice daily (BID)
DRUGPlacebo
Matching liquid placebo, 0 mcg x 2 pumps administered orally twice daily (BID)
Sponsors
Sucampo Pharma Americas, LLC
Takeda
Sucampo AG
Mallinckrodt
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Spontaneous Bowel Movements (SBMs) Within 1 Week | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Consistency of SBMs at Week 1 | 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. |
| Overall Stool Consistency at Week 1 | 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. |
| Mean Change From Baseline in Stool Consistency at Week 1 | Baseline and 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). |
| Overall Straining at Week 1 | Week 1 | Bowel straining was rated on a scale of 0 to 4 (0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe). |
| Mean Change From Baseline in Straining at Week 1 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lubiprostone Participants received liquid formulation of Lubiprostone drug, 12 mcg x 2 pumps administered orally BID. | 82 |
| Placebo Participants received placebo matching the liquid formulation of Lubiprostone drug via pump administered orally BID. | 82 |
| Total | 164 |
Baseline characteristics
| Characteristic | Lubiprostone | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 7 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 78 Participants | 75 Participants | 153 Participants |
| Age, Continuous | 47.2 years STANDARD_DEVIATION 12.51 | 45.0 years STANDARD_DEVIATION 12.82 | 46.1 years STANDARD_DEVIATION 12.68 |
| Body mass index | 29.5 kg/m^2 STANDARD_DEVIATION 5.03 | 30.9 kg/m^2 STANDARD_DEVIATION 6.5 | 30.2 kg/m^2 STANDARD_DEVIATION 5.84 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 29 Participants | 29 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 53 Participants | 53 Participants | 106 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Previous AMITIZA use at randomization No | 80 Participants | 81 Participants | 161 Participants |
| Previous AMITIZA use at randomization Yes | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 42 Participants | 38 Participants | 80 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 38 Participants | 40 Participants | 78 Participants |
| Region of Enrollment United States | 82 participants | 82 participants | 164 participants |
| Sex: Female, Male Female | 55 Participants | 58 Participants | 113 Participants |
| Sex: Female, Male Male | 27 Participants | 24 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 82 | 0 / 82 |
| other Total, other adverse events | 21 / 82 | 15 / 82 |
| serious Total, serious adverse events | 0 / 82 | 0 / 82 |
Outcome results
Primary
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.
Time frame: within 1 week
Population: Modified Intention to Treat (mITT), defined as all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone | Number of Spontaneous Bowel Movements (SBMs) Within 1 Week | 4.6 number of SBMs | Standard Deviation 3.33 |
| Placebo | Number of Spontaneous Bowel Movements (SBMs) Within 1 Week | 4.0 number of SBMs | Standard Deviation 3.5 |
p-value: 0.129ANCOVA
Secondary
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.
Time frame: at Week 1
Population: mITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone | Consistency of SBMs at Week 1 | 3.2 score on a scale | Standard Deviation 3.12 |
| Placebo | Consistency of SBMs at Week 1 | 2.4 score on a scale | Standard Deviation 3.38 |
p-value: 0.129ANCOVA
Secondary
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).
Time frame: Baseline and Week 1
Population: mITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone | Mean Change From Baseline in Stool Consistency at Week 1 | 1.8 Units on a scale | Standard Deviation 0.91 |
| Placebo | Mean Change From Baseline in Stool Consistency at Week 1 | 1.9 Units on a scale | Standard Deviation 0.81 |
p-value: 0.2177ANCOVA
Secondary
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.
Time frame: Week 1
Population: mITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone | Mean Change From Baseline in Straining at Week 1 | -1.1 Units on a scale | Standard Deviation 0.94 |
| Placebo | Mean Change From Baseline in Straining at Week 1 | -0.8 Units on a scale | Standard Deviation 0.82 |
p-value: 0.0664ANCOVA
Secondary
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.
Time frame: at Week 1
Population: mITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone | Overall Stool Consistency at Week 1 | 3.3 score on a scale | Standard Deviation 1.38 |
| Placebo | Overall Stool Consistency at Week 1 | 3.0 score on a scale | Standard Deviation 1.17 |
p-value: 0.2177ANCOVA
Secondary
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).
Time frame: Week 1
Population: mITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone | Overall Straining at Week 1 | 1.8 Units on a scale | Standard Deviation 0.91 |
| Placebo | Overall Straining at Week 1 | 1.9 Units on a scale | Standard Deviation 0.81 |
p-value: 0.0664ANCOVA