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

• ClinicalTrials.gov Identifier: NCT02473640
• Recruitment Status: Completed
• First Posted: June 16, 2015
• Results First Posted: February 19, 2018
• Last Update Posted: November 27, 2018
• Sponsor: Synthetic Biologics Inc.
• Information provided by (Responsible Party): Synthetic Biologics Inc.

Study Description

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

Condition or disease	Intervention/treatment	Phase
Healthy Volunteers With Ileostomy	Drug: SYN-004; Drug: Esomeprazole; Drug: Ceftriaxone	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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 Start Date: June 2015
• Actual Primary Completion Date: April 2016
• Actual Study Completion Date: April 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Ceftriaxone Concentration in Intestinal Chyme Period 1 [ Time Frame: 0-8.5 hours ]
   Ceftriaxone concentration in the presence of SYN-004 and the absence of esomeprazole.
2. Ribaxamase Concentration in Intestinal Chyme Period 1 [ Time Frame: 0-8.5 hours ]
   Concentrations of ribaximase (SYN-004) in intestinal chyme
3. Ceftriaxone Concentration in Intestinal Chyme Period 2 [ Time Frame: 0-8.5 hours ]
   Ceftriaxone concentration in the presence of SYN-004 and the absence of esomeprazole.
4. Ribaxamase Concentration in Intestinal Chyme Period 2 [ Time Frame: 0-8.5 hours ]
   Concentrations of ribaximase (SYN-004) in intestinal chyme

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Canada, Alberta

Synthetic Biologics Investigative Site

Edmonton, Alberta, Canada

Canada

Synthetic Biologics Investigative Site

Montreal, Canada

Sponsors and Collaborators

Synthetic Biologics Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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 β-Lactamase SYN-004 (Ribaxamase) Degrades Ceftriaxone Excreted into the Intestine in Phase 2a Clinical Studies. Antimicrob Agents Chemother. 2017 Feb 23;61(3). pii: e02197-16. doi: 10.1128/AAC.02197-16. Print 2017 Mar.

• Responsible Party: Synthetic Biologics Inc.
• ClinicalTrials.gov Identifier: NCT02473640
• Other Study ID Numbers: SB-1-004-004
• First Posted: June 16, 2015
• Results First Posted: February 19, 2018
• Last Update Posted: November 27, 2018
• Last Verified: October 2018

Additional relevant MeSH terms:

Ceftriaxone; Esomeprazole; Anti-Ulcer Agents; Gastrointestinal Agents; Proton Pump Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Bacterial Agents; Anti-Infective Agents