A Study Evaluating the Effect of Esomeprazole on SYN-004 Degradation of Ceftriaxone In Adults With an Ileostomy

Phase 1

Completed

Conditions: Healthy Volunteers With Ileostomy

Interventions: Drug: SYN-004
Drug: Esomeprazole
Drug: Ceftriaxone

Registration Number: NCT02473640

Lead Sponsor: Theriva Biologics, Inc.

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 15

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
150 mg SYN-004	Esomeprazole	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.
150 mg SYN-004	Ceftriaxone	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.
150 mg SYN-004	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.

Primary Outcome Measures

Name	Time	Method
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 1	0-8.5 hours	Ceftriaxone concentration in the presence of SYN-004 and the absence of esomeprazole.
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