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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers With Ileostomy
• Intervention / Treatment: Drug: Esomeprazole; Drug: SYN-004; Drug: Ceftriaxone

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).

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Montreal, Canada
    • Synthetic Biologics Investigative Site
  • Alberta
    • Edmonton, Alberta, Canada
      • Synthetic Biologics Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: Esomeprazole; Drug: SYN-004; Drug: Ceftriaxone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ceftriaxone Concentration in Intestinal Chyme Period 1	Ceftriaxone concentration in the presence of SYN-004 and the absence of esomeprazole.	0-8.5 hours
Ribaxamase Concentration in Intestinal Chyme Period 1	Concentrations of ribaximase (SYN-004) in intestinal chyme	0-8.5 hours
Ceftriaxone Concentration in Intestinal Chyme Period 2	Ceftriaxone concentration in the presence of SYN-004 and the absence of esomeprazole.	0-8.5 hours
Ribaxamase Concentration in Intestinal Chyme Period 2	Concentrations of ribaximase (SYN-004) in intestinal chyme	0-8.5 hours

Collaborators and Investigators

• Sponsor: Synthetic Biologics Inc.

Publications and helpful links

General Publications

• Kokai-Kun JF, Roberts T, Coughlin O, Sicard E, Rufiange M, Fedorak R, Carter C, Adams MH, Longstreth J, Whalen H, Sliman J. The Oral beta-Lactamase SYN-004 (Ribaxamase) Degrades Ceftriaxone Excreted into the Intestine in Phase 2a Clinical Studies. Antimicrob Agents Chemother. 2017 Feb 23;61(3):e02197-16. doi: 10.1128/AAC.02197-16. Print 2017 Mar.

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: June 12, 2015
• First Submitted That Met QC Criteria: June 15, 2015
• First Posted (Estimate): June 16, 2015

Study Record Updates

• Last Update Posted (Actual): November 27, 2018
• Last Update Submitted That Met QC Criteria: October 31, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Ceftriaxone; Esomeprazole
• Other Study ID Numbers: SB-1-004-004