Irritable Bowel Syndrome
Conditions
Brief summary
A study of the efficacy and safety of Lubiprostone in subjects diagnosed with IBS-M/IBS-U.
Detailed description
To assess the efficacy and safety of oral lubiprostone, as compared to matching placebo, when administered orally (at 8 mcg twice daily \[BID\]) in subjects diagnosed with IBS-M/IBS-U.
Interventions
DRUGLubiprostone
8 mcg administered orally twice daily (BID)
DRUGPlacebo
Matching placebo, 0 mcg administered orally twice daily (BID)
Sponsors
Takeda
Sucampo AG
Sucampo Pharma Americas, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Care provider and outcomes assessor were also blinded
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject meets the diagnosis of IBS-M or IBS-U as confirmed using the adapted ROME III Diagnostic Questionnaire for Adult Functional GI Disorders. * Subject Screening diary entries must show an average worst abdominal pain in the past 24 hours score of at least 4 on a 11-point scale. * Subject must be on a stable dose of selective serotonin re-uptake inhibitors (SSRIs), serotonin-specific reuptake inhibitor (SNRIs), or monoamine oxidase inhibitors (MAO) inhibitors if taking antidepressants.
Exclusion criteria
* Subject has current diagnosis of IBS with diarrhea (IBS-D) or IBS with constipation (IBS-C), according to Rome III Criteria. * Any gastrointestinal (GI) condition, other than IBS-related, 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 Participants Classified as an Overall Responder for Abdominal Pain | within 12 weeks | An overall responder for abdominal pain is defined as a participant who is a weekly responder for at least 75% of observed treatment weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Classified as a Monthly Responder for Abdominal Pain | within 3 months | A monthly responder for abdominal pain is defined as a participant who is a weekly responder for abdominal pain at least 2 of 4 weeks in the preceding month. |
| Number of Participants Classified as a Weekly Responder for Stool Consistency | within 12 weeks | A weekly responder for stool consistency is defined as a participant having at least 50% reduction from baseline in percentage of days with extreme stool consistency for a given week. |
| Number of Participants Classified as a Monthly Responder for Stool Consistency | within 3 months | A monthly responder for stool consistency is defined as a participant who is a weekly responder for stool consistency at least 2 of 4 weeks in the preceding month. |
| Number of Participants Classified as a Weekly Responder for Abdominal Pain | within 12 weeks | Participants rate their pain on a pain intensity scale where 0=no pain and 10=worst pain. A higher score means the pain is worse. A weekly responder for abdominal pain is defined as a participant reporting ≥ 30% reduction from baseline in average of 24-hour worst abdominal pain scores for the preceding week. |
| Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | within 12 weeks | A participant who achieves adequate relief of IBS symptoms during the preceding week is classified as a weekly responder for IBS symptoms. |
| Number of Participants Classified as a Monthly Responder for IBS Symptoms | within 3 months | A participant who is a weekly responder for IBS symptoms for at least 2 of the 4 weeks in the preceding month is classified as a monthly responder for IBS symptoms. |
| Number of Participants Classified as an Overall Responder for IBS Symptoms | within 3 months | A participant who is a weekly responder for IBS symptoms for at least 75% of observed treatment weeks is classified as an overall responder for IBS symptoms. |
| Number of Participants Classified as an Overall Responder for Stool Consistency | within 3 months | An overall responder for stool consistency is defined as a participant who qualifies as a weekly responder for stool consistency for at least 75% of observed treatment weeks. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants receive 0 mcg capsules twice daily (BID) | 34 |
| Lubiprostone Participants receive 8 mcg lubiprostone capsules BID | 37 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 4 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Placebo | Lubiprostone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 34 Participants | 65 Participants |
| Age, Continuous | 45 years | 49 years | 48 years |
| Baseline Abdominal Pain | 5.90 units on a scale STANDARD_DEVIATION 1.34 | 5.37 units on a scale STANDARD_DEVIATION 1.406 | 5.62 units on a scale STANDARD_DEVIATION 1.39 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 4 Participants | 11 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 26 Participants | 33 Participants | 59 Participants |
| Region of Enrollment United States | 34 participants | 37 participants | 71 participants |
| Sex: Female, Male Female | 26 Participants | 32 Participants | 58 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 37 |
| other Total, other adverse events | 8 / 34 | 12 / 37 |
| serious Total, serious adverse events | 0 / 34 | 1 / 37 |
Outcome results
Primary
Number of Participants Classified as an Overall Responder for Abdominal Pain
An overall responder for abdominal pain is defined as a participant who is a weekly responder for at least 75% of observed treatment weeks.
Time frame: within 12 weeks
Population: modified Intent to Treat (mITT), defined as all randomized subjects who take at least one dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Classified as an Overall Responder for Abdominal Pain | 10 Participants |
| Lubiprostone | Number of Participants Classified as an Overall Responder for Abdominal Pain | 11 Participants |
Comparison: P-value is from a Cochran-Mantel-Haenszel (CMH) test stratified by sex and baseline stool consistencyp-value: =0.987Cochran-Mantel-Haenszel
Secondary
Number of Participants Classified as a Monthly Responder for Abdominal Pain
A monthly responder for abdominal pain is defined as a participant who is a weekly responder for abdominal pain at least 2 of 4 weeks in the preceding month.
Time frame: within 3 months
Population: mITT
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Classified as a Monthly Responder for Abdominal Pain | Month 1 | 12 Participants |
| Placebo | Number of Participants Classified as a Monthly Responder for Abdominal Pain | Month 2 | 16 Participants |
| Placebo | Number of Participants Classified as a Monthly Responder for Abdominal Pain | Month 3 | 15 Participants |
| Lubiprostone | Number of Participants Classified as a Monthly Responder for Abdominal Pain | Month 1 | 14 Participants |
| Lubiprostone | Number of Participants Classified as a Monthly Responder for Abdominal Pain | Month 2 | 16 Participants |
| Lubiprostone | Number of Participants Classified as a Monthly Responder for Abdominal Pain | Month 3 | 13 Participants |
Secondary
Number of Participants Classified as a Monthly Responder for IBS Symptoms
A participant who is a weekly responder for IBS symptoms for at least 2 of the 4 weeks in the preceding month is classified as a monthly responder for IBS symptoms.
Time frame: within 3 months
Population: mITT
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Classified as a Monthly Responder for IBS Symptoms | Month 2 | 20 Participants |
| Placebo | Number of Participants Classified as a Monthly Responder for IBS Symptoms | Month 3 | 17 Participants |
| Placebo | Number of Participants Classified as a Monthly Responder for IBS Symptoms | Month 1 | 21 Participants |
| Lubiprostone | Number of Participants Classified as a Monthly Responder for IBS Symptoms | Month 2 | 18 Participants |
| Lubiprostone | Number of Participants Classified as a Monthly Responder for IBS Symptoms | Month 3 | 15 Participants |
| Lubiprostone | Number of Participants Classified as a Monthly Responder for IBS Symptoms | Month 1 | 16 Participants |
Secondary
Number of Participants Classified as a Monthly Responder for Stool Consistency
A monthly responder for stool consistency is defined as a participant who is a weekly responder for stool consistency at least 2 of 4 weeks in the preceding month.
Time frame: within 3 months
Population: mITT
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Classified as a Monthly Responder for Stool Consistency | Month 1 | 3 Participants |
| Placebo | Number of Participants Classified as a Monthly Responder for Stool Consistency | Month 2 | 12 Participants |
| Placebo | Number of Participants Classified as a Monthly Responder for Stool Consistency | Month 3 | 7 Participants |
| Lubiprostone | Number of Participants Classified as a Monthly Responder for Stool Consistency | Month 1 | 12 Participants |
| Lubiprostone | Number of Participants Classified as a Monthly Responder for Stool Consistency | Month 2 | 9 Participants |
| Lubiprostone | Number of Participants Classified as a Monthly Responder for Stool Consistency | Month 3 | 7 Participants |
Secondary
Number of Participants Classified as an Overall Responder for IBS Symptoms
A participant who is a weekly responder for IBS symptoms for at least 75% of observed treatment weeks is classified as an overall responder for IBS symptoms.
Time frame: within 3 months
Population: mITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Classified as an Overall Responder for IBS Symptoms | 11 Participants |
| Lubiprostone | Number of Participants Classified as an Overall Responder for IBS Symptoms | 10 Participants |
Secondary
Number of Participants Classified as an Overall Responder for Stool Consistency
An overall responder for stool consistency is defined as a participant who qualifies as a weekly responder for stool consistency for at least 75% of observed treatment weeks.
Time frame: within 3 months
Population: mITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Classified as an Overall Responder for Stool Consistency | 0 Participants |
| Lubiprostone | Number of Participants Classified as an Overall Responder for Stool Consistency | 3 Participants |
Secondary
Number of Participants Classified as a Weekly Responder for Abdominal Pain
Participants rate their pain on a pain intensity scale where 0=no pain and 10=worst pain. A higher score means the pain is worse. A weekly responder for abdominal pain is defined as a participant reporting ≥ 30% reduction from baseline in average of 24-hour worst abdominal pain scores for the preceding week.
Time frame: within 12 weeks
Population: mITT
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 2 | 13 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 7 | 14 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 4 | 13 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 8 | 11 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 1 | 7 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 9 | 13 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 5 | 15 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 10 | 15 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 11 | 14 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 3 | 11 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 12 | 10 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 6 | 16 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 12 | 12 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 1 | 7 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 2 | 8 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 3 | 12 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 4 | 19 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 5 | 18 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 6 | 15 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 7 | 14 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 8 | 18 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 9 | 15 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 11 | 14 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Abdominal Pain | Week 10 | 12 Participants |
Secondary
Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms
A participant who achieves adequate relief of IBS symptoms during the preceding week is classified as a weekly responder for IBS symptoms.
Time frame: within 12 weeks
Population: mITT
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 4 | 21 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 2 | 16 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 8 | 17 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 6 | 19 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 9 | 18 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 3 | 18 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 10 | 15 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 7 | 16 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 11 | 18 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 5 | 22 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 12 | 4 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 1 | 14 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 12 | 6 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 3 | 15 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 4 | 20 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 5 | 19 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 6 | 17 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 7 | 17 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 1 | 9 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 8 | 20 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 9 | 14 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 10 | 15 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 11 | 14 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Irritable Bowel Syndrome (IBS) Symptoms | Week 2 | 14 Participants |
Secondary
Number of Participants Classified as a Weekly Responder for Stool Consistency
A weekly responder for stool consistency is defined as a participant having at least 50% reduction from baseline in percentage of days with extreme stool consistency for a given week.
Time frame: within 12 weeks
Population: mITT
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 10 | 8 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 5 | 11 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 1 | 5 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 6 | 8 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 2 | 6 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 7 | 8 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 9 | 6 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 3 | 5 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 11 | 7 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 8 | 6 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 12 | 8 Participants |
| Placebo | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 4 | 7 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 12 | 8 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 8 | 9 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 9 | 5 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 2 | 11 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 3 | 10 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 4 | 10 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 5 | 9 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 6 | 7 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 7 | 9 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 10 | 10 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 11 | 6 Participants |
| Lubiprostone | Number of Participants Classified as a Weekly Responder for Stool Consistency | Week 1 | 12 Participants |