Constipation
Conditions
Brief summary
The objective of this study is to evaluate multiple doses of BLI801 Laxative for safety and efficacy versus placebo in adults experiencing non-idiopathic constipation.
Interventions
DRUGBLI801 Laxative
BLI801 oral laxative
DRUGBLI801 Placebo
BLI801 oral laxative placebo
Sponsors
Braintree Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 84 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects between the ages of \> 18 and \< 85 years 2. Constipated, defined by the following criteria: Fewer than 3 spontaneous defecations per week and at least one of the following symptoms for the previous 4 weeks: * Straining during \> 25% of defecations * Lumpy or hard stools in \> 25% of defecations * Sensation of incomplete evacuation for \> 25% of defecations 3. Receiving a stable maintenance opioid regimen. 4. If female, and of child-bearing potential, is using an acceptable form of birth control 5. Negative pregnancy test at screening (Visit 1), if applicable 6. In the Investigator's judgment, subject is mentally competent to provide informed consent to participate in the study
Exclusion criteria
1. Subjects with known or suspected ileus, gastrointestinal obstruction, gastric retention, bowel perforation, toxic colitis or toxic megacolon 2. Subjects who have had major surgery within 30 days before Visit 1; appendectomy or cholecystectomy 60 days before Visit 1; abdominal, pelvic, or retroperitoneal surgery 6 months before Visit 1; bariatric surgery or surgery to remove a segment of the GI tract at any time before Visit 1 3. Medical conditions associated with diarrhea, intermittent loose stools or constipation, which could confound the interpretation of the results, eg, fecal incontinence or irritable bowel syndrome. Subjects with irritable bowel syndrome (IBS) that has been previously diagnosed by a physician prior to initiation of the constipating therapy and that meets the following criteria, are excluded: 1. Absence of a structural or biochemical explanation for the abdominal pain symptom 2. At least 12 weeks during a period of 12 months, of abdominal discomfort or pain with at least 2 of the following 3 features: i. Relieved with defecation, and/or ii. Onset associated with a change in frequency of stool, and/or iii. Onset associated with a change in form of stool. 4. Subjects diagnosed with chronic constipation prior to initiation of opioid treatment 5. Subjects taking laxatives (with the exception of fiber supplements), prokinetic agents or antidiarrheal drugs and refuse to discontinue these treatments from Visit 1 until after completion of Visit 5 6. Subjects who are pregnant or nursing, or intend to become pregnant during the study 7. Subjects of childbearing potential who refuse a pregnancy test 8. Subjects who are allergic to any BLI801 component 9. Subjects taking non-opioid medications or supplements known to cause constipation 10. Subjects with an active history of drug or alcohol abuse 11. Subjects who have participated in an investigational clinical, surgical, drug, or device study within the past 30 days 12. Subjects who, in the opinion of the Investigator, should not be included in the study for any reason, including inability to follow study procedures. 13. Subjects who have had a colonoscopy within 2 weeks of Visit 1 or are scheduled to have a colonoscopy during their participation in the study. 14. Subjects who withdraw consent at any time prior to completion of Visit 1 procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| % of Subjects With Treatment Response | 12 weeks | Treatment response is defined as subjects who are weekly responders for at least 9 out of 12 weeks, with at least 3 of these weeks occurring in the last 4 weeks of treatment. A weekly responder is a subject who has ≥ 3 spontaneous bowel movements (SBMs) and an increase from baseline of \> 1 SBM in that week. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BLI801 Laxative (High Dose) BLI801 Laxative (high dose)
BLI801 Laxative: BLI801 oral laxative | 114 |
| BLI801 Laxative (Mid Dose) BLI801 Laxative (mid dose)
BLI801 Laxative: BLI801 oral laxative | 104 |
| BLI801 Laxative (Low Dose) BLI801 Laxative (low dose)
BLI801 Laxative: BLI801 oral laxative | 114 |
| BLI801 Placebo BLI801 Placebo
BLI801 Placebo: BLI801 oral laxative placebo | 99 |
| Total | 431 |
Baseline characteristics
| Characteristic | BLI801 Laxative (High Dose) | BLI801 Laxative (Mid Dose) | BLI801 Laxative (Low Dose) | BLI801 Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 55.6 years STANDARD_DEVIATION 9.03 | 53.8 years STANDARD_DEVIATION 10.43 | 53.4 years STANDARD_DEVIATION 10.62 | 55.7 years STANDARD_DEVIATION 10.61 | 54.6 years STANDARD_DEVIATION 10.19 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 9 Participants | 10 Participants | 4 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 104 Participants | 95 Participants | 104 Participants | 95 Participants | 398 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 69 Participants | 69 Participants | 80 Participants | 71 Participants | 289 Participants |
| Sex: Female, Male Male | 45 Participants | 35 Participants | 34 Participants | 28 Participants | 142 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 / 114 | 0 / 104 | 0 / 114 | 0 / 99 |
| other Total, other adverse events | 24 / 114 | 15 / 104 | 23 / 114 | 20 / 99 |
| serious Total, serious adverse events | 3 / 114 | 2 / 104 | 3 / 114 | 2 / 99 |
Outcome results
Primary
% of Subjects With Treatment Response
Treatment response is defined as subjects who are weekly responders for at least 9 out of 12 weeks, with at least 3 of these weeks occurring in the last 4 weeks of treatment. A weekly responder is a subject who has ≥ 3 spontaneous bowel movements (SBMs) and an increase from baseline of \> 1 SBM in that week.
Time frame: 12 weeks
Population: The Primary Efficacy Analysis Population is based on the modified Intent-to-Treat population which includes patients who were randomized and took at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BLI801 Laxative (High Dose) | % of Subjects With Treatment Response | Success | 42 Participants |
| BLI801 Laxative (High Dose) | % of Subjects With Treatment Response | Fail | 72 Participants |
| BLI801 Laxative (Mid Dose) | % of Subjects With Treatment Response | Fail | 70 Participants |
| BLI801 Laxative (Mid Dose) | % of Subjects With Treatment Response | Success | 34 Participants |
| BLI801 Laxative (Low Dose) | % of Subjects With Treatment Response | Success | 30 Participants |
| BLI801 Laxative (Low Dose) | % of Subjects With Treatment Response | Fail | 84 Participants |
| BLI801 Placebo | % of Subjects With Treatment Response | Fail | 79 Participants |
| BLI801 Placebo | % of Subjects With Treatment Response | Success | 20 Participants |
p-value: 0.034Cochran-Mantel-Haenszel