A Study to Evaluate the Effect of SYN-004 on the PK of IV Ceftriaxone in Adults With a Functioning Ileostomy

A Phase 1b/2a, Randomized, Multi-center, Open-label, Fixed-sequence Study to Evaluate the Effect of Oral SYN-004 on the Pharmacokinetics of Intravenous Ceftriaxone in Healthy Adult Subjects With a Functioning Ileostomy

A Phase 1b/2a, Randomized, Multi-Center, Open-Label, Fixed-Sequence Study to Evaluate the Effect of Oral SYN-004 on the Pharmacokinetics of Intravenous Ceftriaxone in Healthy Adult Subjects with a Functioning Ileostomy.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Period 1 - Treatment Sequence AB; Drug: Period 1 - Treatment Sequence AC; Drug: Period 2 - Treatment Sequence AB; Drug: Period 2 - Treatment Sequence AC

Detailed Description

This is a Phase 1b/2a, randomized, multi-center, open-label study. Twenty otherwise healthy subjects between the ages of 18 and 80 years, inclusive, with functioning ileostomies were planned to be enrolled. In the first treatment period (Period 1) all subjects received an IV infusion of 1 g ceftriaxone. Subjects had a 3 - 7 day washout period between Period 1 and Period 2. In the second treatment period (Period 2) all subjects received an IV infusion of 1 g ceftriaxone and 2 oral doses of either 75 or 150 mg of SYN-004, according to the randomization schedule, which were administered 30 minutes before and 5.5 hours after the start of the ceftriaxone infusion.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Montreal, Canada
  • Alberta
    • Edmonton, Alberta, Canada
• United States
  • Ohio
    • Columbus, Ohio, United States, 43210

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The subject has a functioning ileostomy which has been in place for > 3 months.
2. Male or female between the ages of 18 and 70 years, inclusive.
3. Other than a functioning ileostomy, the subject is free from clinically significant illnesses or disease.

Exclusion Criteria:

1. Subjects who have active hepatic, small intestine, or biliary tract disease.
2. Subjects who have active ulcerative colitis, Crohn's disease, other inflammatory bowel disease.
3. Subjects with known malignancy requiring treatment < 6 months prior to study screening.
4. Subjects who have, in the opinion of the investigator, significant concurrent medical illness.
5. Subjects who are currently taking concomitant medications which may interfere with study evaluation.
6. 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.
7. Subjects with a known history of allergy to any cephalosporin, penicillin or any β-lactam antibiotic.
8. Subjects who have known active malabsorption syndromes(s) that, in the judgment of the investigator, could compromise the objectives of the study.
9. Subjects who have used any oral, intramuscular, or IV anti-microbial medication during the last 3 weeks prior to the screening visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period 1 - Treatment Sequence AB; Treatment Sequence AB: Period 1: Ceftriaxone 1 g infused IV over 30 minutes; [Period 2: Ceftriaxone 1 g infused IV over 30 minutes and SYN-004 75 mg (1 x 75 mg capsule) orally administered 30 minutes before and 5.5 hours after the start of the ceftriaxone infusion]	Drug: Period 1 - Treatment Sequence AB; Period 1: Ceftriaxone 1 g infused IV over 30 minutes only, no SYN-004
Experimental: Period 1 - Treatment Sequence AC; Period 1: Ceftriaxone 1 g infused IV over 30 minutes; [Period 2: Ceftriaxone 1 g infused IV over 30 minutes and SYN-004 150 mg (2 x 75 mg capsules) orally administered 30 minutes before and 5.5 hours after the start of the ceftriaxone infusion]	Drug: Period 1 - Treatment Sequence AC; Period 1: Ceftriaxone 1 g infused IV over 30 minutes only, no SYN-004
Experimental: Period 2 - Treatment Sequence AB; Treatment Sequence AB: [Period 1: Ceftriaxone 1 g infused IV over 30 minutes]; Period 2: Ceftriaxone 1 g infused IV over 30 minutes and SYN-004 75 mg (1 x 75 mg capsule) orally administered 30 minutes before and 5.5 hours after the start of the ceftriaxone infusion	Drug: Period 2 - Treatment Sequence AB; Period 2: Ceftriaxone 1 g infused IV over 30 minutes and SYN-004 75 mg; Other Names: ribaxamase
Experimental: Period 2 - Treatment Sequence AC; [Period 1: Ceftriaxone 1 g infused IV over 30 minutes]; Period 2: Ceftriaxone 1 g infused IV over 30 minutes and SYN-004 150 mg (2 x 75 mg capsules) orally administered 30 minutes before and 5.5 hours after the start of the ceftriaxone infusion	Drug: Period 2 - Treatment Sequence AC; Period 2: Ceftriaxone 1 g infused IV over 30 minutes and SYN-004 150 mg; Other Names: ribaxamase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ceftriaxone PK Maximum Observed Plasma Concentration (Cmax) With (Period 2) and Without (Period 1) SYN-004.		2 weeks
Ceftriaxone PK Time to Reach Cmax (Tmax) With (Period 2) and Without (Period 1) SYN-004.	Samples were collected at 0.25 h, 0.5 through 2 h, and 3 through 7 h after the infusion start. Standard deviations may be 0 if all collected T max values occur at the same time.	2 weeks
Ceftriaxone PK Area Under the Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUCt) With (Period 2) and Without (Period 1) SYN-004.		2 weeks

Collaborators and Investigators

• Sponsor: Synthetic Biologics Inc.
• Investigators: Study Chair: Michael Kaleko, M.D., Synthetic Biologics

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: March 1, 2015
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: April 1, 2015
• First Submitted That Met QC Criteria: April 15, 2015
• First Posted (Estimate): April 17, 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

• Other Study ID Numbers: SB-1-004-003