Chronic Idiopathic Constipation
Conditions
Brief summary
This is a study of efficacy and safety of Plecanatide in pediatric subjects aged 12 to \< 18 years diagnosed with Chronic Idiopathic Constipation.
Detailed description
The purpose of the study is to evaluate efficacy, safety, and pharmacokinetics (PK) of oral Plecanatide 0.5, 1.0 and 1.5 mg tablets dosed once a day as compared to matching placebo, when administered for 8 weeks in adolescents with chronic idiopathic constipation. This study will consist of a 4-week screening period, 8 weeks of treatment, and a 2-week follow-up. The study will assess the effects of Plecanatide on bowel movement frequency and other clinical features of CIC.
Interventions
DRUGPlecanatide
DRUGMatching placebo
Sponsors
Bausch Health Americas, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Male or female adolescents 12 to less than 18 years of age. 2. Diagnosed with CIC based on the Rome III criteria for child/adolescent functional constipation (Appendix A). 3. Patient is able to voluntarily provide written, signed, and dated (personally and via a legally authorized representative \[LAR\]) assent/informed consent as applicable to participate in the study. 4. Subject's parent/LAR demonstrates an understanding, ability, and willingness to fully comply with study procedures (e.g., accept venipuncture, willing and able to swallow tablets, accept urine drug screen for opiates) and restrictions. Key
Exclusion criteria
1. The patient has a mental age \<4 years in the investigator's opinion. 2. The patient has previously been diagnosed with anorectal malformations, neurological deficits, or anatomical anomalies that would constitute a predisposition to constipation. 3. The patient currently requires iron supplements, amitriptyline, or other tricyclic antidepressants for depression, opioid-containing medications or compounds for pain, or has other conditions that require medications known to cause constipation. A patient with an onset of constipation prior to the use of these medications and who has been on a stable dose for at least 8 weeks prior to Screening might be considered eligible for this study if the investigator deems these medications do not significantly contribute to the patient's constipation. Screening of these patients needs to be approved by the medical monitor and the sponsor. 4. The patient, if female of childbearing potential (defined as postmenarche), does not agree to practice 1 of the following medically acceptable methods of birth control throughout the study: * Hormonal methods such as oral, implantable, injectable, vaginal ring, or transdermal contraceptives for a minimum of 1 full cycle (based on the patient's usual menstrual cycle period) before study drug administration. * Total abstinence from sexual intercourse since the last menses before study drug administration. * Intrauterine device. * Double barrier method (condoms, sponge, or diaphragm with spermicidal jellies or cream. 5. The patient follows a diet not considered normal by the investigator for the patient's age, relative to variety of food, caloric content, and quantity. The patient must have been on a stable diet for at least 30 days weeks prior to Screening. 6. The patient's mobility or normal exercise tolerance is compromised in the investigator's opinion. 7. The patient has a history of an eating disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Overall Responders | 8 weeks | An Overall Responder is a participant who was a Spontaneous Bowel Movement (SBM) responder for the last 2 weeks of the Treatment Period. An SBM responder is defined as a participant who had \>3 SBMs per week. SBM was defined as a bowel movement that occurs in the absence of laxative use within the preceding 24 hours. Participants missing with respect to the outcome measure were scored as non-responders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weekly Average Stool Consistency Bristol Stool Form Scale (BSFS) Score | 8 weeks | Stool consistency was assessed via the 7-point (1-7) Bristol Stool Form Scale (BSFS) and recorded in the bowel movement (BM) and Symptom Diaries. Lower numbers represent more formed stools; higher numbers represent less formed stools. The weekly mean BSFS score per patient = (total of all BSFS scores reported for a corresponding Spontaneous Bowel Movement (SBM) per time period)/n, where n = number of SBMs scored during the time period. Baseline was the mean BSFS score recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. BSFS types were 1) separate hard lumps, like nuts (hard to pass); 2) sausage-shaped but lumpy; 3) like a sausage but with cracks on its surface; 4) like a sausage or snake, smooth and soft; 5) soft blobs with clear-cut edges (passed easily); 6) fluffy pieces with ragged edges, a mushy stool; 7) watery, no solid pieces, entirely liquid. |
| Change From Baseline in the Weekly Rate of Spontaneous Bowel Movements (SBM) | 8 weeks | The weekly Spontaneous Bowel Movement (SBM) totals were derived from the daily diary entries reported during the Treatment Period in the Bowel Movement (BM) and symptom diaries. Baseline was the mean number of SBMs recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. SBM is defined as a bowel movement that occurs in the absence of laxative use within the preceding 24 hours |
| Change From Baseline in the Weekly Rate of Complete Spontaneous Bowel Movements (CSBM) | 8 weeks | The weekly Complete Spontaneous Bowel Movement (CSBM) totals are derived from the daily diary entries reported during the Treatment Period in the Bowel Movement (BM) and symptom diaries. Baseline is the mean number of CSBMs recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. Spontaneous Bowel Movement (SBM) was defined as a bowel movement that occurs in the absence of laxative use within the preceding 24 hours. CSBM was defined as a spontaneous bowel movement with the sense of complete evacuation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Matching Placebo Taken orally once daily in the morning for 8 weeks
Matching placebo | 31 |
| Plecanatide 0.5 mg Taken orally once daily in the morning for 8 weeks
Plecanatide | 31 |
| Plecanatide 1.0 mg Taken orally once daily in the morning for 8 weeks
Plecanatide | 30 |
| Plecanatide 1.5 mg Taken orally once daily in the morning for 8 weeks
Plecanatide | 32 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 | 1 | 1 |
| Overall Study | Other | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 3 | 2 |
Baseline characteristics
| Characteristic | Matching Placebo | Plecanatide 0.5 mg | Plecanatide 1.0 mg | Plecanatide 1.5 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 14.6 years STANDARD_DEVIATION 1.61 | 15.1 years STANDARD_DEVIATION 1.48 | 14.5 years STANDARD_DEVIATION 1.89 | 14.6 years STANDARD_DEVIATION 1.52 | 14.7 years STANDARD_DEVIATION 1.62 |
| Baseline Stool Consistency | 2.17 units on a scale STANDARD_DEVIATION 0.932 | 2.0 units on a scale STANDARD_DEVIATION 1.19 | 2.08 units on a scale STANDARD_DEVIATION 0.899 | 2.29 units on a scale STANDARD_DEVIATION 1.298 | 2.13 units on a scale STANDARD_DEVIATION 1.14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 21 Participants | 21 Participants | 23 Participants | 27 Participants | 92 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 10 Participants | 7 Participants | 5 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 5 Participants | 3 Participants | 2 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 24 Participants | 27 Participants | 29 Participants | 104 Participants |
| Region of Enrollment United States | 31 participants | 31 participants | 30 participants | 32 participants | 124 participants |
| Sex: Female, Male Female | 17 Participants | 17 Participants | 17 Participants | 18 Participants | 69 Participants |
| Sex: Female, Male Male | 14 Participants | 14 Participants | 13 Participants | 14 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 31 | 0 / 30 | 0 / 32 |
| other Total, other adverse events | 4 / 31 | 7 / 31 | 4 / 30 | 3 / 32 |
| serious Total, serious adverse events | 0 / 31 | 0 / 31 | 0 / 30 | 0 / 32 |
Outcome results
Primary
Proportion of Overall Responders
An Overall Responder is a participant who was a Spontaneous Bowel Movement (SBM) responder for the last 2 weeks of the Treatment Period. An SBM responder is defined as a participant who had \>3 SBMs per week. SBM was defined as a bowel movement that occurs in the absence of laxative use within the preceding 24 hours. Participants missing with respect to the outcome measure were scored as non-responders.
Time frame: 8 weeks
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Matching Placebo | Proportion of Overall Responders | 7 Participants |
| Plecanatide 0.5 mg | Proportion of Overall Responders | 10 Participants |
| Plecanatide 1.0 mg | Proportion of Overall Responders | 12 Participants |
| Plecanatide 1.5 mg | Proportion of Overall Responders | 7 Participants |
Secondary
Change From Baseline in the Weekly Rate of Complete Spontaneous Bowel Movements (CSBM)
The weekly Complete Spontaneous Bowel Movement (CSBM) totals are derived from the daily diary entries reported during the Treatment Period in the Bowel Movement (BM) and symptom diaries. Baseline is the mean number of CSBMs recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. Spontaneous Bowel Movement (SBM) was defined as a bowel movement that occurs in the absence of laxative use within the preceding 24 hours. CSBM was defined as a spontaneous bowel movement with the sense of complete evacuation.
Time frame: 8 weeks
Population: All randomized participants
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Matching Placebo | Change From Baseline in the Weekly Rate of Complete Spontaneous Bowel Movements (CSBM) | 1.30 Weekly CSBMs | Standard Error 0.344 |
| Plecanatide 0.5 mg | Change From Baseline in the Weekly Rate of Complete Spontaneous Bowel Movements (CSBM) | 1.71 Weekly CSBMs | Standard Error 0.348 |
| Plecanatide 1.0 mg | Change From Baseline in the Weekly Rate of Complete Spontaneous Bowel Movements (CSBM) | 1.83 Weekly CSBMs | Standard Error 0.354 |
| Plecanatide 1.5 mg | Change From Baseline in the Weekly Rate of Complete Spontaneous Bowel Movements (CSBM) | 2.11 Weekly CSBMs | Standard Error 0.34 |
Secondary
Change From Baseline in the Weekly Rate of Spontaneous Bowel Movements (SBM)
The weekly Spontaneous Bowel Movement (SBM) totals were derived from the daily diary entries reported during the Treatment Period in the Bowel Movement (BM) and symptom diaries. Baseline was the mean number of SBMs recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. SBM is defined as a bowel movement that occurs in the absence of laxative use within the preceding 24 hours
Time frame: 8 weeks
Population: All randomized participants
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Matching Placebo | Change From Baseline in the Weekly Rate of Spontaneous Bowel Movements (SBM) | 1.44 Weekly SBMs | Standard Error 0.332 |
| Plecanatide 0.5 mg | Change From Baseline in the Weekly Rate of Spontaneous Bowel Movements (SBM) | 1.97 Weekly SBMs | Standard Error 0.339 |
| Plecanatide 1.0 mg | Change From Baseline in the Weekly Rate of Spontaneous Bowel Movements (SBM) | 2.06 Weekly SBMs | Standard Error 0.343 |
| Plecanatide 1.5 mg | Change From Baseline in the Weekly Rate of Spontaneous Bowel Movements (SBM) | 2.05 Weekly SBMs | Standard Error 0.328 |
Secondary
Change From Baseline in Weekly Average Stool Consistency Bristol Stool Form Scale (BSFS) Score
Stool consistency was assessed via the 7-point (1-7) Bristol Stool Form Scale (BSFS) and recorded in the bowel movement (BM) and Symptom Diaries. Lower numbers represent more formed stools; higher numbers represent less formed stools. The weekly mean BSFS score per patient = (total of all BSFS scores reported for a corresponding Spontaneous Bowel Movement (SBM) per time period)/n, where n = number of SBMs scored during the time period. Baseline was the mean BSFS score recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. BSFS types were 1) separate hard lumps, like nuts (hard to pass); 2) sausage-shaped but lumpy; 3) like a sausage but with cracks on its surface; 4) like a sausage or snake, smooth and soft; 5) soft blobs with clear-cut edges (passed easily); 6) fluffy pieces with ragged edges, a mushy stool; 7) watery, no solid pieces, entirely liquid.
Time frame: 8 weeks
Population: All randomized participants
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Matching Placebo | Change From Baseline in Weekly Average Stool Consistency Bristol Stool Form Scale (BSFS) Score | 0.98 units on a scale | Standard Error 0.209 |
| Plecanatide 0.5 mg | Change From Baseline in Weekly Average Stool Consistency Bristol Stool Form Scale (BSFS) Score | 1.09 units on a scale | Standard Error 0.209 |
| Plecanatide 1.0 mg | Change From Baseline in Weekly Average Stool Consistency Bristol Stool Form Scale (BSFS) Score | 1.22 units on a scale | Standard Error 0.205 |
| Plecanatide 1.5 mg | Change From Baseline in Weekly Average Stool Consistency Bristol Stool Form Scale (BSFS) Score | 1.06 units on a scale | Standard Error 0.191 |