Constipation - Functional
Conditions
Brief summary
Study to determine if children (6-17 years old) with functional constipation will respond to being treated with lubiprostone for 12 weeks.
Detailed description
Dose administration details: * Participants with a body weight \<50 kg at baseline received Lubiprostone 12 mcg BID for 12 weeks. If the dose was safe but did not show any efficacy at Week 1, dosage was increased to 24 mcg BID. * Participants with a body weight \>50 kg at baseline received Lubiprostone 24 mcg BID for 12 weeks. If the dose was unsafe at Week 1, dosage was decreased to 12 mcg BID.
Interventions
DRUGLubiprostone
12 or 24 mcg soft capsules of lubiprostone for oral administration, depending on baseline weight and response during week 1
DRUGPlacebo
0 mcg soft capsules of placebo for oral administration
Sponsors
Sucampo AG
Sucampo Pharma Americas, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
While the care provider and outcomes assessor were also blinded, this was classified as a double-blind trial
Intervention model description
Placebo controlled
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Medically-confirmed diagnosis of Functional Constipation per Rome III Diagnostic Criteria for Childhood Functional Constipation * At least 6 years of age but less than 18 years of age at the time of randomisation * Only stable dose of selective serotonin re-uptake inhibitors (SSRIs), serotonin-specific reuptake inhibitor (SNRIs), or monoamine oxidase inhibitors (MAO) inhibitors are allowed if subject is taking antidepressants
Exclusion criteria
* Any gastrointestinal (GI) condition, other than constipation and/or irritable bowel syndrome (IBS), affecting GI motility or defecation * Untreated faecal impaction at the time of screening * 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 Overall Responders at Week 12 | at Week 12 | An overall responder is defined as a participant who qualified as a weekly responder for 9 of the 12 treatment weeks, with durability demonstrated by at least 3 of the responder weeks occurring during the last 4 weeks of the treatment period. A weekly responder is defined as a participant who has at least 3 spontaneous bowel movements during the week, and at least one more than at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Number of SBMs Observed Each Week for 12 Weeks | within 12 Weeks | Data provided is based on observed cases. Baseline is the average of the 2 weeks before being randomized. Participants are summarized by actual dose received after week 1. |
Countries
Belgium, Canada, France, Netherlands, Poland, United Kingdom, United States
Participant flow
Pre-assignment details
The two weeks between screening and treatment were used as a washout period for disallowed medications.
Participants by arm
| Arm | Count |
|---|---|
| Lubiprostone Participants receive lubiprostone BID up to 12 weeks | 404 |
| Placebo Participants receive placebo BID up to 12 weeks | 202 |
| Total | 606 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 17 | 6 |
| Overall Study | Lack of Efficacy | 4 | 3 |
| Overall Study | Lost to Follow-up | 9 | 2 |
| Overall Study | Non-compliance with Study Drug | 2 | 3 |
| Overall Study | Other | 3 | 3 |
| Overall Study | Physician Decision | 7 | 2 |
| Overall Study | Site Terminated by Sponsor | 2 | 1 |
| Overall Study | Withdrawal by Subject | 21 | 16 |
Baseline characteristics
| Characteristic | Lubiprostone | Placebo | Total |
|---|---|---|---|
| Age, Customized 10-13 years | 153 Participants | 78 Participants | 231 Participants |
| Age, Customized 14-17 years | 104 Participants | 51 Participants | 155 Participants |
| Age, Customized 6-9 years | 142 Participants | 66 Participants | 208 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 76 Participants | 44 Participants | 120 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 323 Participants | 151 Participants | 474 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 67 Participants | 39 Participants | 106 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 20 Participants | 11 Participants | 31 Participants |
| Race (NIH/OMB) White | 308 Participants | 138 Participants | 446 Participants |
| Region of Enrollment Belgium | 1 participants | 3 participants | 4 participants |
| Region of Enrollment Canada | 5 participants | 7 participants | 12 participants |
| Region of Enrollment France | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Netherlands | 14 participants | 32 participants | 46 participants |
| Region of Enrollment Poland | 3 participants | 8 participants | 11 participants |
| Region of Enrollment United Kingdom | 4 participants | 6 participants | 10 participants |
| Region of Enrollment United States | 174 participants | 348 participants | 522 participants |
| Sex: Female, Male Female | 216 Participants | 106 Participants | 322 Participants |
| Sex: Female, Male Male | 183 Participants | 89 Participants | 272 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 400 | 0 / 195 |
| other Total, other adverse events | 234 / 400 | 82 / 195 |
| serious Total, serious adverse events | 11 / 400 | 7 / 195 |
Outcome results
Primary
Number of Participants Classified as Overall Responders at Week 12
An overall responder is defined as a participant who qualified as a weekly responder for 9 of the 12 treatment weeks, with durability demonstrated by at least 3 of the responder weeks occurring during the last 4 weeks of the treatment period. A weekly responder is defined as a participant who has at least 3 spontaneous bowel movements during the week, and at least one more than at baseline.
Time frame: at Week 12
Population: mITT population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lubiprostone | Number of Participants Classified as Overall Responders at Week 12 | 76 Participants |
| Placebo | Number of Participants Classified as Overall Responders at Week 12 | 28 Participants |
p-value: 0.1609Cochran-Mantel-Haenszel
Secondary
Mean Number of SBMs Observed Each Week for 12 Weeks
Data provided is based on observed cases. Baseline is the average of the 2 weeks before being randomized. Participants are summarized by actual dose received after week 1.
Time frame: within 12 Weeks
Population: mITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 2 | 2.68 Spontaneous bowel movements | Standard Deviation 2.422 |
| Lubiprostone | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 7 | 2.81 Spontaneous bowel movements | Standard Deviation 2.483 |
| Lubiprostone | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 4 | 2.94 Spontaneous bowel movements | Standard Deviation 2.531 |
| Lubiprostone | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 8 | 2.94 Spontaneous bowel movements | Standard Deviation 2.501 |
| Lubiprostone | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 1 | 2.65 Spontaneous bowel movements | Standard Deviation 2.137 |
| Lubiprostone | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 9 | 2.83 Spontaneous bowel movements | Standard Deviation 2.286 |
| Lubiprostone | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 5 | 2.91 Spontaneous bowel movements | Standard Deviation 2.498 |
| Lubiprostone | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 10 | 2.68 Spontaneous bowel movements | Standard Deviation 2.326 |
| Lubiprostone | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 3 | 2.85 Spontaneous bowel movements | Standard Deviation 2.446 |
| Lubiprostone | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 11 | 2.78 Spontaneous bowel movements | Standard Deviation 2.251 |
| Lubiprostone | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 6 | 2.91 Spontaneous bowel movements | Standard Deviation 2.454 |
| Lubiprostone | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 12 | 2.90 Spontaneous bowel movements | Standard Deviation 2.497 |
| Lubiprostone | Mean Number of SBMs Observed Each Week for 12 Weeks | at Baseline | 1.40 Spontaneous bowel movements | Standard Deviation 0.836 |
| Placebo | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 12 | 2.75 Spontaneous bowel movements | Standard Deviation 2.53 |
| Placebo | Mean Number of SBMs Observed Each Week for 12 Weeks | at Baseline | 1.42 Spontaneous bowel movements | Standard Deviation 0.855 |
| Placebo | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 1 | 2.50 Spontaneous bowel movements | Standard Deviation 2.117 |
| Placebo | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 2 | 2.69 Spontaneous bowel movements | Standard Deviation 2.328 |
| Placebo | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 3 | 2.59 Spontaneous bowel movements | Standard Deviation 2.435 |
| Placebo | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 4 | 2.69 Spontaneous bowel movements | Standard Deviation 2.499 |
| Placebo | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 5 | 2.68 Spontaneous bowel movements | Standard Deviation 2.495 |
| Placebo | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 6 | 2.65 Spontaneous bowel movements | Standard Deviation 2.163 |
| Placebo | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 7 | 2.75 Spontaneous bowel movements | Standard Deviation 2.704 |
| Placebo | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 8 | 2.64 Spontaneous bowel movements | Standard Deviation 2.444 |
| Placebo | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 9 | 2.37 Spontaneous bowel movements | Standard Deviation 1.875 |
| Placebo | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 10 | 2.40 Spontaneous bowel movements | Standard Deviation 2.103 |
| Placebo | Mean Number of SBMs Observed Each Week for 12 Weeks | at Week 11 | 2.60 Spontaneous bowel movements | Standard Deviation 2.362 |