Irritable Bowel Syndrome With Constipation (IBS-C)
Conditions
Brief summary
A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multi-Dose Study of the Effect of Two Dosage Strengths of SYN-010 Compared with Placebo on Breath Methane Production in Breath Methane-Positive Subjects with Irritable Bowel Syndrome with Constipation (IBS-C)
Detailed description
This is a Phase 2, randomized, multi-center, multi-dose study. Sixty subjects with irritable bowel syndrome with constipation who are between the ages of 18 and 65, inclusive, will be enrolled. The entire duration of the study may be up to 43 days (from Screening to the post end-of-study \[EOS\] visit telephone call).
Interventions
Sponsors
Theriva Biologics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must have IBS-C and have a positive breath CH4 test result (\> 10 ppm) at Screening. * Subject must meet the modified Rome III criteria for IBS-C. * Subject must have an average abdominal pain intensity score of ≥ 3 (scale 0-10) reported at Screening and Baseline. * Subject must have an average of fewer than 3 complete spontaneous bowel movement (CSBMs) per week. * Subject must agree to refrain from making any lifestyle changes that may affect IBS-C symptoms from the time of Screening to the end of the study.
Exclusion criteria
* Subject has taken IBS treatments (prescription or over-the-counter), proton pump inhibitors, laxatives, antibiotics. * Subject currently has any structural abnormality of the gastrointestinal (GI) tract or a disease or condition that can affect GI motility, or any unexplained and clinically significant symptoms such as lower GI bleeding, rectal bleeding, heme-positive stool, iron-deficiency anemia, weight loss, or systemic signs of infection. * Subject has been diagnosed with or has a family history of familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, or any other form of familial colorectal cancer. * Subject reports loose (mushy) or watery stools (Bristol Stool Form Scale \[BSFS\] score of 6 or 7).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in the Area Under the Curve (AUC) of Breath CH4 Production at Day 7 | 7 days |
Countries
United States
Participant flow
Pre-assignment details
79 subjects were randomized into the study per IVRS. 63 subjects received at least one dose of SYN-010. 16/79 subjects were not administered a single dose of study drug or placebo. We considered the subject truly randomized once the subject had completed the breath methane test, completed the daily diary entries, and were assigned study drug.
Participants by arm
| Arm | Count |
|---|---|
| Low Dose 21 mg SYN-010 | 22 |
| High Dose 42 mg SYN-010 | 19 |
| Placebo Placebo | 22 |
| Total | 63 |
Baseline characteristics
| Characteristic | Low Dose | High Dose | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 42.6 years STANDARD_DEVIATION 6.01 | 44.7 years STANDARD_DEVIATION 9.54 | 46.4 years STANDARD_DEVIATION 10.29 | 44.6 years STANDARD_DEVIATION 8.78 |
| Sex: Female, Male Female | 19 Participants | 14 Participants | 17 Participants | 50 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 22 | 2 / 19 | 1 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 19 | 0 / 22 |
Outcome results
Primary
Change From Baseline in the Area Under the Curve (AUC) of Breath CH4 Production at Day 7
Time frame: 7 days
Population: 79 subjects consented/randomized to treatment. 63 dosed subjects. 59 subjects (21, 20 \& 18 for the placebo, 21mg and 42mg, respectively) were included for the analysis of AUC on Day 7, and the subjects with missing CH4 values at either baseline or Day 7 were excluded from the analysis since the area under the curve could not be calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose | Change From Baseline in the Area Under the Curve (AUC) of Breath CH4 Production at Day 7 | 99.2 hours*ppm | Standard Deviation 79.4 |
| High Dose | Change From Baseline in the Area Under the Curve (AUC) of Breath CH4 Production at Day 7 | 57.3 hours*ppm | Standard Deviation 43.1 |
| Placebo | Change From Baseline in the Area Under the Curve (AUC) of Breath CH4 Production at Day 7 | 72.7 hours*ppm | Standard Deviation 53.5 |