Chronic Idiopathic Constipation, CIC, Constipation
Conditions
Brief summary
The objective of this study is to evaluate a daily dose of BLI400 Laxative for safety and efficacy versus placebo in constipated adults.
Interventions
DRUGBLI400 Laxative
21 gm BLI400 powder
DRUGBLI400 Placebo
Equivalent amount of placebo powder
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 No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects at least 18 years of age 2. Constipated, defined by the following adapted ROME II definition Fewer than 3 spontaneous defecations per week and at least one of the following symptoms for at least 12 weeks (which need not be consecutive) in the preceding 12 months: * Straining during \> 25% of defecations * Lumpy or hard stools in \> 25% of defecations * Sensation of incomplete evacuation for \> 25% of defecations 3. If female, and of child-bearing potential, is using an acceptable form of birth control 4. Negative serum pregnancy test at screening, if applicable 5. In the Investigator's judgment, subject is mentally competent to provide informed consent to participate in the study
Exclusion criteria
1. Report loose (mushy) or water stools in the absence of laxative use for more than 25% of BMs during the 12 weeks before Visit 1 2. Meet the Rome II criteria for Irritable Bowel Syndrome. 3. Subjects with known or suspected ileus, gastrointestinal obstruction, gastric retention, bowel perforation, toxic colitis, toxic megacolon 4. Subjects who have had major surgery 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 5. Subjects with hypothyroidism that is being treated and for which the dose of thyroid hormone has not been stable for at least 6 weeks at the time of Visit 1 6. Subjects taking laxatives, enemas or prokinetic agents that refuse to discontinue these treatments from Visit 1 until after completion of the study 7. Subjects who are pregnant or lactating, or intend to become pregnant during the study 8. Subjects of childbearing potential who refuse a pregnancy test 9. Subjects who are allergic to any study medication component 10. Subjects taking narcotic analgesics or other medications known to cause constipation 11. Subjects with clinically significant cardiac abnormalities identified at the Visit 1 ECG 12. Subjects with clinically significant laboratory abnormalities, deemed as a potential safety issue by the Investigator 13. Subjects who, in the opinion of the Investigator, should not be included in the study for any reason, including inability to follow study procedures 14. Subjects who have participated in an investigational clinical, surgical, drug, or device study within the past 30 days 15. Subjects with an active history of drug or alcohol abuse 16. Subjects have been hospitalized for a psychiatric condition or have made a suicide attempt during the 2 years before Visit 1 17. Subjects who withdraw consent at any time prior to completion of Visit 1 procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Response | 12 weeks | The primary endpoint is the proportion of 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 CSBMs and an increase from baseline of \> 1 CSBM in that week. |
Countries
United States
Participant flow
Pre-assignment details
1020 subjects were consented and entered into a two-week run-in period to confirm constipation status (subjects were required to average \< 3 complete spontaneous bowel movements per week). Following the run-in period, 603 subjects qualified for randomization.
Participants by arm
| Arm | Count |
|---|---|
| BLI400 Laxative BLI400 Laxative (21 gm BLI400 powder) | 299 |
| Placebo BLI400 placebo (equivalent amount of placebo powder) | 304 |
| Total | 603 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 10 |
| Overall Study | Lack of Efficacy | 5 | 8 |
| Overall Study | Lost to Follow-up | 12 | 14 |
| Overall Study | Physician Decision | 5 | 5 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 25 | 13 |
Baseline characteristics
| Characteristic | BLI400 Laxative | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 52.4 years STANDARD_DEVIATION 15.3 | 51.7 years STANDARD_DEVIATION 15.6 | 51.0 years STANDARD_DEVIATION 15.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 119 Participants | 233 Participants | 114 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 180 Participants | 370 Participants | 190 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 19 Participants | 40 Participants | 21 Participants |
| Race (NIH/OMB) Black or African American | 88 Participants | 189 Participants | 101 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 8 Participants | 3 Participants |
| Race (NIH/OMB) White | 187 Participants | 365 Participants | 178 Participants |
| Region of Enrollment United States | 299 participants | 603 participants | 304 participants |
| Sex: Female, Male Female | 221 Participants | 460 Participants | 239 Participants |
| Sex: Female, Male Male | 78 Participants | 143 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 299 | 0 / 304 |
| other Total, other adverse events | 42 / 299 | 33 / 304 |
| serious Total, serious adverse events | 3 / 299 | 8 / 304 |
Outcome results
Primary
Treatment Response
The primary endpoint is the proportion of 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 CSBMs and an increase from baseline of \> 1 CSBM in that week.
Time frame: 12 weeks
Population: modified ITT population - excludes subjects with significant protocol violations
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BLI400 Laxative | Treatment Response | 77 Participants |
| Placebo | Treatment Response | 39 Participants |
p-value: <0.001Cochran-Mantel-Haenszel