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

NCT02473640 | Completed Phase 1 Results

• 1 other identifier: SB-1-004-004
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

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

Conditions

Healthy Volunteers With Ileostomy

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (1)

150 mg SYN-004

EXPERIMENTAL

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

Interventions

SYN-004 DRUG

150 mg SYN-004

Esomeprazole DRUG

150 mg SYN-004

Ceftriaxone DRUG

150 mg SYN-004

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Theriva Biologics, Inc.: lead

Study Sites (2)

Synthetic Biologics Investigative Site

Edmonton, Alberta, Canada

Location

Synthetic Biologics Investigative Site

Montreal, Canada

Location

Related Publications (1)

• 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.

  PMID: 28052855 DERIVED

MeSH Terms

Interventions

SYN-004; Esomeprazole; Ceftriaxone

Intervention Hierarchy (Ancestors)

Omeprazole; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Thiazines

Results Point of Contact

• Title: Michael Kaleko, M.D.
• Organization: Synthetic Biologics Inc.

mkaleko@syntheticbiologics.com

(240) 238-3862

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2015
• First Posted: June 16, 2015
• Study Start: June 1, 2015
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: November 27, 2018
• Results First Posted: February 19, 2018

Record last verified: 2018-10

Locations

CA (2)