Non-cancer Pain, Opioid Induced Constipation
Conditions
Keywords
Opioid induced constipation/prucalopride chronic non-cancer pain, Subjects with chronic non-cancer pain suffering from OIC
Brief summary
The study will evaluate the efficacy, safety and tolerability of prucalopride over 12 weeks of treatment in subjects aged 18 years and older with chronic non-cancer pain, suffering from opioid induced constipation.
Interventions
DRUGplacebo
placebo
DRUGprucalopride
1 or 2 mg prucalopride once daily before breakfast
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
to be assessed at screening: 1. Male or non-pregnant, non-breast-feeding female outpatient ≥18 years. 2. Has chronic pain of any aetiology (except cancer pain) requiring daily maintenance treatment with opioids;has been on stable daily opioid dose during at least the previous 2 weeks; and is expected to remain on stable daily dose of opioids for at least 15 weeks after Visit 1. 3. Subject is suffering from OIC (i.e. secondary to chronic opioid use). 4. Subject agrees to stop his/her laxative treatment and is willing to use rescue medication. Main
Exclusion criteria
to be assessed at screening: 1. Constipation is thought to be drug-induced (except for opioids) 2. Disallowed medication is being used 3. Subject was on chronic therapy for chronic constipation prior to start of opioid therapy 4. Subject is suffering from secondary causes of chronic constipation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subjects With an Average Frequency of >=3 Spontaneous Bowel Movements Per Week | 12 weeks | A bowel movement (BM) was defined as spontaneous if no laxatives were taken in the 24 hours preceding that BM. |
Secondary
| Measure | Time frame |
|---|---|
| Plasma Concentration of Prucalopride at Week 2 | Week 2 |
| Plasma Concentration of Prucalopride at Week 8 | Week 8 |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo once daily before breakfast for up to 12 weeks | 83 |
| Prucalopride 1 or 2 mg prucalopride once daily before breakfast for up to 12 weeks | 86 |
| Total | 169 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 3 |
| Overall Study | Convenience issue | 1 | 0 |
| Overall Study | Did not meet in-/exclusion criteria | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Randomized by mistake | 0 | 1 |
| Overall Study | Sponsor's decision | 3 | 1 |
| Overall Study | Surgical procedure | 0 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | Placebo | Prucalopride | Total |
|---|---|---|---|
| Age, Continuous | 57.7 years STANDARD_DEVIATION 11.67 | 55.7 years STANDARD_DEVIATION 12.15 | 56.7 years STANDARD_DEVIATION 11.92 |
| Age, Customized >=75 years | 10 Participants | 9 Participants | 19 Participants |
| Age, Customized Between >=18 and <65 years | 62 Participants | 66 Participants | 128 Participants |
| Age, Customized Between >=65 and <75 years | 11 Participants | 11 Participants | 22 Participants |
| Region of Enrollment Belgium | 8 Participants | 9 Participants | 17 Participants |
| Region of Enrollment Bulgaria | 4 Participants | 5 Participants | 9 Participants |
| Region of Enrollment Czech Republic | 40 Participants | 38 Participants | 78 Participants |
| Region of Enrollment France | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment Germany | 6 Participants | 7 Participants | 13 Participants |
| Region of Enrollment Hungary | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment Netherlands | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Poland | 6 Participants | 5 Participants | 11 Participants |
| Region of Enrollment Romania | 5 Participants | 6 Participants | 11 Participants |
| Region of Enrollment United Kingdom | 13 Participants | 14 Participants | 27 Participants |
| Sex: Female, Male Female | 61 Participants | 62 Participants | 123 Participants |
| Sex: Female, Male Male | 22 Participants | 24 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 83 | 30 / 86 |
| serious Total, serious adverse events | 2 / 83 | 2 / 86 |
Outcome results
Primary
Percent of Subjects With an Average Frequency of >=3 Spontaneous Bowel Movements Per Week
A bowel movement (BM) was defined as spontaneous if no laxatives were taken in the 24 hours preceding that BM.
Time frame: 12 weeks
Population: Intent-to-Treat (ITT) population includes all subjects who were randomized into the study and who had received at least 1 dose of investigational medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent of Subjects With an Average Frequency of >=3 Spontaneous Bowel Movements Per Week | 39.8 percentage of subjects |
| Prucalopride | Percent of Subjects With an Average Frequency of >=3 Spontaneous Bowel Movements Per Week | 48.8 percentage of subjects |
p-value: 0.305Cochran-Mantel-Haenszel
Secondary
Plasma Concentration of Prucalopride at Week 2
Time frame: Week 2
Population: ITT (subjects in the ITT whose post-dose samples were collected outside the 5-hour sampling window were not used in the plasma concentration calculation)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentration of Prucalopride at Week 2 | pre-dose | 2.827 ng/ml | Standard Deviation 1.5989 |
| Placebo | Plasma Concentration of Prucalopride at Week 2 | 5 hours post-dose | 6.107 ng/ml | Standard Deviation 2.8839 |
Secondary
Plasma Concentration of Prucalopride at Week 8
Time frame: Week 8
Population: ITT (subjects in the ITT whose post-dose samples were collected outside the 5-hour sampling window were not used in the plasma concentration calculation)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentration of Prucalopride at Week 8 | pre-dose | 3.179 ng/ml | Standard Deviation 1.9066 |
| Placebo | Plasma Concentration of Prucalopride at Week 8 | 5 hours post-dose | 6.615 ng/ml | Standard Deviation 2.5758 |