Opioid-induced Bowel Dysfunction
Conditions
Brief summary
The primary purpose of the study is to evaluate the efficacy and safety of lubiprostone administration in subjects with Opioid-induced Bowel Dysfunction.
Interventions
DRUGLubiprostone
24 mcg administered orally twice daily (BID)
DRUGPlacebo
Matching placebo, 0 mcg administered orally twice daily (BID)
Sponsors
Sucampo Pharmaceuticals, Inc.
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 for this double-blind trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
A patient can be considered for eligibility to participate if he/she: * Has been consistently treated for chronic, noncancer-related pain with any oral, transdermal, intravenous, or subcutaneous opioid for at least 30 days prior to screening * Is diagnosed with OBD * Is capable of utilizing an electronic diary to report daily spontaneous bowel movements (SBMs) * Is willing to continue opioid therapy and discontinue the use of laxatives, stool softeners, and other concomitant medications affecting gastrointestinal motility throughout the study
Exclusion criteria
A patient cannot be considered for eligibility to participate if he/she: * Uses opioids for the treatment of cancer-related pain, abdominal pain, mechanical bowel obstructions, bowel disorders, and constipation not arising from opioid use, but instead attributable to dietary, neurologic, congenital, or endocrine disorders, scleroderma, and/or for the management of drug addiction
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Classified as Treatment Responders Within 12 Weeks | 12 weeks | Spontaneous bowel movement (SBM) is defined as any BM that does not occur within 24 hours after use of rescue medication. To be classified as responders, participants are required to demonstrate at least moderate response (≥ 1 SBM improvement over baseline SBM frequency) for all treatment weeks for which observed data are available, and must additionally demonstrate a full response (≥ 3 SBMs per week) for at least 9 of the 12 treatment weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of SBMs Per Week at Week 8 | at Week 8 | — |
| Number of Participants Who Experienced First SBM Within 48 Hours After Dose Initiation | within 48 hours post-dose | — |
| Number of SBMs Per Week at Week 12 | at Week 12 | — |
| Number of SBMs Per Week Overall | within 14 weeks | Overall is defined as the length of time from first dose to last follow-up within 2 weeks after last dose. |
Countries
Belgium, Czechia, Germany, Poland, Sweden, United Kingdom, United States
Participant flow
Recruitment details
Recruitment period: 07 December 2010 to 16 November 2011 Recruitment sites: 91 U.S. investigative sites and 14 E.U. investigative sites
Pre-assignment details
Safety evaluable population includes all subjects who were randomized and dosed. Intention to treat (ITT) population includes only those subjects who were dosed and provided at least one post-treatment efficacy assessment.
Participants by arm
| Arm | Count |
|---|---|
| Lubiprostone 24 mcg capsules twice daily (BID)
Lubiprostone: 24 mcg administered orally twice daily (BID) | 219 |
| Placebo 0 mcg capsules twice daily (BID)
Placebo: Matching placebo, 0 mcg administered orally twice daily (BID) | 220 |
| Total | 439 |
Baseline characteristics
| Characteristic | Lubiprostone | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 51.9 years STANDARD_DEVIATION 9.01 | 51.5 years STANDARD_DEVIATION 11.68 | 51.7 years STANDARD_DEVIATION 10.42 |
| Region of Enrollment Belgium | 2 participants | 2 participants | 4 participants |
| Region of Enrollment Czech Republic | 6 participants | 8 participants | 14 participants |
| Region of Enrollment Germany | 4 participants | 3 participants | 7 participants |
| Region of Enrollment Poland | 2 participants | 2 participants | 4 participants |
| Region of Enrollment United Kingdom | 3 participants | 2 participants | 5 participants |
| Region of Enrollment United States | 202 participants | 203 participants | 405 participants |
| Sex: Female, Male Female | 138 Participants | 138 Participants | 276 Participants |
| Sex: Female, Male Male | 81 Participants | 82 Participants | 163 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 219 | 0 / 220 |
| other Total, other adverse events | 72 / 219 | 44 / 220 |
| serious Total, serious adverse events | 7 / 219 | 6 / 220 |
Outcome results
Primary
Number of Participants Classified as Treatment Responders Within 12 Weeks
Spontaneous bowel movement (SBM) is defined as any BM that does not occur within 24 hours after use of rescue medication. To be classified as responders, participants are required to demonstrate at least moderate response (≥ 1 SBM improvement over baseline SBM frequency) for all treatment weeks for which observed data are available, and must additionally demonstrate a full response (≥ 3 SBMs per week) for at least 9 of the 12 treatment weeks.
Time frame: 12 weeks
Population: Intention to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lubiprostone | Number of Participants Classified as Treatment Responders Within 12 Weeks | 59 Participants |
| Placebo | Number of Participants Classified as Treatment Responders Within 12 Weeks | 41 Participants |
Secondary
Number of Participants Who Experienced First SBM Within 48 Hours After Dose Initiation
Time frame: within 48 hours post-dose
Population: Intention to treat
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lubiprostone | Number of Participants Who Experienced First SBM Within 48 Hours After Dose Initiation | within 24 Hours | 110 Participants |
| Lubiprostone | Number of Participants Who Experienced First SBM Within 48 Hours After Dose Initiation | within 48 Hours | 157 Participants |
| Placebo | Number of Participants Who Experienced First SBM Within 48 Hours After Dose Initiation | within 24 Hours | 84 Participants |
| Placebo | Number of Participants Who Experienced First SBM Within 48 Hours After Dose Initiation | within 48 Hours | 134 Participants |
Secondary
Number of SBMs Per Week at Week 12
Time frame: at Week 12
Population: Intention to treat with data at Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone | Number of SBMs Per Week at Week 12 | 3.1 SBMs/week | Standard Deviation 3.13 |
| Placebo | Number of SBMs Per Week at Week 12 | 2.7 SBMs/week | Standard Deviation 3.34 |
Secondary
Number of SBMs Per Week at Week 8
Time frame: at Week 8
Population: Intention to treat with data at Week 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone | Number of SBMs Per Week at Week 8 | 2.9 SBMs/week | Standard Deviation 3.18 |
| Placebo | Number of SBMs Per Week at Week 8 | 2.5 SBMs/week | Standard Deviation 3.03 |
Secondary
Number of SBMs Per Week Overall
Overall is defined as the length of time from first dose to last follow-up within 2 weeks after last dose.
Time frame: within 14 weeks
Population: Intention to treat with data at Week 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lubiprostone | Number of SBMs Per Week Overall | 4.3 SBMs/week | Standard Deviation 2.96 |
| Placebo | Number of SBMs Per Week Overall | 3.7 SBMs/week | Standard Deviation 2.53 |