Healthy Volunteers With Ileostomy
Conditions
Brief summary
A Phase 1b/2a, Multi-Center, Open-Label, 2-Period, Fixed-Sequence Study Evaluating the Effect of Esomeprazole on SYN-004 Degradation of Ceftriaxone In Healthy Adult Subjects with a Functioning Ileostomy
Detailed description
This is a Phase 1b/2a, randomized, multi-center, open-label study. Twenty otherwise healthy subjects with functioning ileostomies who are between the ages of 18 and 80 years, inclusive, will be enrolled. The entire duration of the study may be up to 63 days (from Screening to the end-of-study \[EOS\] visit).
Interventions
Sponsors
Theriva Biologics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* The subject has a functioning ileostomy that has been in place for ≥ 3 months. * The subject is male or female between the ages of 18 and 80 years, inclusive. * Other than a functioning ileostomy, the subject is free from clinically significant illnesses or disease.
Exclusion criteria
* Subjects who have active hepatic, small intestine, or biliary tract disease. * Subjects who have active ulcerative colitis, Crohn's disease, other inflammatory bowel disease. * Subjects with known malignancy requiring treatment \< 6 months prior to study screening. * Subjects who have, in the opinion of the investigator, significant concurrent medical illness. * Subjects who are currently taking concomitant medications which may interfere with study evaluation. * Subjects who have received an investigational drug within 30 days or within a time period consistent with a washout period of 5 half-lives, whichever is longer, of the first dose of ceftriaxone. * Subjects with a known history of allergy to any cephalosporin, penicillin or any β-lactam antibiotic. * Subjects who have known active malabsorption syndromes(s) that, in the judgment of the investigator, could compromise the objectives of the study. * Subjects who have used any oral, intramuscular, or IV anti-microbial medication during the last 3 week
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ceftriaxone Concentration in Intestinal Chyme Period 1 | 0-8.5 hours | Ceftriaxone concentration in the presence of SYN-004 and the absence of esomeprazole. |
| Ribaxamase Concentration in Intestinal Chyme Period 1 | 0-8.5 hours | Concentrations of ribaximase (SYN-004) in intestinal chyme |
| Ceftriaxone Concentration in Intestinal Chyme Period 2 | 0-8.5 hours | Ceftriaxone concentration in the presence of SYN-004 and the absence of esomeprazole. |
| Ribaxamase Concentration in Intestinal Chyme Period 2 | 0-8.5 hours | Concentrations of ribaximase (SYN-004) in intestinal chyme |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 150 mg SYN-004 There will be 2 in-house treatment periods: in Treatment Period 1, subjects will receive 2 oral doses of 150 mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone, and in Treatment Period 2, subjects will receive 2 oral doses of 150mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone in the presence of steady-state esomeprazole; Treatment Periods 1 and 2 will be separated by a 5- to 7-day run-in phase, during which subjects will self-administer 40 mg of esomeprazole once daily (QD) in the morning, at home.
SYN-004
Esomeprazole
Ceftriaxone | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Treatment Period 1 | Adverse Event | 1 |
Baseline characteristics
| Characteristic | 150 mg SYN-004 |
|---|---|
| Age, Continuous | 45.1 years STANDARD_DEVIATION 16.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 3 / 15 | 3 / 14 | 2 / 14 |
| serious Total, serious adverse events | 0 / 15 | 0 / 14 | 0 / 14 |
Outcome results
Primary
Ceftriaxone Concentration in Intestinal Chyme Period 1
Ceftriaxone concentration in the presence of SYN-004 and the absence of esomeprazole.
Time frame: 0-8.5 hours
Population: Subjects with functioning illeostomies who received a single IV infusion of 1 g ceftriaxone.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 1 | Hour 0 | 0.00 ug/mL | Standard Error 0 |
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 1 | Hour 0.5 | 0.00 ug/mL | Standard Error 0 |
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 1 | Hour 1.5 | 5.60 ug/mL | Standard Error 4.39 |
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 1 | Hour 2.5 | 150.90 ug/mL | Standard Error 68.43 |
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 1 | Hour 3.5 | 231.40 ug/mL | Standard Error 144.06 |
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 1 | Hour 4.5 | 173.00 ug/mL | Standard Error 98.58 |
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 1 | Hour 5.5 | 29.00 ug/mL | Standard Error 25.4 |
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 1 | Hour 6.5 | 1.40 ug/mL | Standard Error 0.82 |
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 1 | Hour 7.5 | 0.10 ug/mL | Standard Error 0.1 |
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 1 | Hour 8.5 | 2.00 ug/mL | Standard Error 1.7 |
Primary
Ceftriaxone Concentration in Intestinal Chyme Period 2
Ceftriaxone concentration in the presence of SYN-004 and the absence of esomeprazole.
Time frame: 0-8.5 hours
Population: Subjects with functioning illeostomies who received a single IV infusion of 1 g ceftriaxone.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 2 | Hour 0 | 0.00 ug/mL | Standard Error 0 |
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 2 | Hour 0.5 | 0.00 ug/mL | Standard Error 0 |
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 2 | Hour 1.5 | 9.80 ug/mL | Standard Error 8.43 |
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 2 | Hour 2.5 | 31.70 ug/mL | Standard Error 22.57 |
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 2 | Hour 3.5 | 42.80 ug/mL | Standard Error 30.44 |
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 2 | Hour 4.5 | 80.50 ug/mL | Standard Error 56.28 |
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 2 | Hour 5.5 | 0.80 ug/mL | Standard Error 0.63 |
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 2 | Hour 6.5 | 0.10 ug/mL | Standard Error 0.1 |
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 2 | Hour 7.5 | 0.00 ug/mL | Standard Error 0 |
| 150 mg SYN-004 | Ceftriaxone Concentration in Intestinal Chyme Period 2 | Hour 8.5 | 0.20 ug/mL | Standard Error 0.14 |
Primary
Ribaxamase Concentration in Intestinal Chyme Period 1
Concentrations of ribaximase (SYN-004) in intestinal chyme
Time frame: 0-8.5 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 1 | Hour 0 | 0.00 ng/mL | Standard Error 0 |
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 1 | Hour 0.5 | 2 ng/mL | Standard Error 2.1 |
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 1 | Hour 1.5 | 11 ng/mL | Standard Error 9.1 |
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 1 | Hour 2.5 | 131 ng/mL | Standard Error 116.8 |
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 1 | Hour 3.5 | 6727 ng/mL | Standard Error 3983.1 |
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 1 | Hour 4.5 | 56795 ng/mL | Standard Error 25155.4 |
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 1 | Hour 5.5 | 73090 ng/mL | Standard Error 29292.8 |
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 1 | Hour 6.5 | 103171 ng/mL | Standard Error 52510.2 |
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 1 | Hour 7.5 | 153274 ng/mL | Standard Error 87804.1 |
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 1 | Hour 8.5 | 111946 ng/mL | Standard Error 71722.7 |
Primary
Ribaxamase Concentration in Intestinal Chyme Period 2
Concentrations of ribaximase (SYN-004) in intestinal chyme
Time frame: 0-8.5 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 2 | Hour 0.5 | 436 ng/mL | Standard Error 435.6 |
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 2 | Hour 1.5 | 281 ng/mL | Standard Error 206.6 |
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 2 | Hour 0 | 0.00 ng/mL | Standard Error 0 |
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 2 | Hour 2.5 | 97745 ng/mL | — |
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 2 | Hour 3.5 | 66936 ng/mL | Standard Error 46358.5 |
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 2 | Hour 4.5 | 63696 ng/mL | Standard Error 26962.2 |
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 2 | Hour 5.5 | 42316 ng/mL | Standard Error 15114.4 |
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 2 | Hour 6.5 | 38874 ng/mL | Standard Error 21552 |
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 2 | Hour 7.5 | 34756 ng/mL | Standard Error 19642.6 |
| 150 mg SYN-004 | Ribaxamase Concentration in Intestinal Chyme Period 2 | Hour 8.5 | 35092 ng/mL | Standard Error 20734.9 |