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

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: Period 1 - Treatment Sequence AB; Drug: Period 1 - Treatment Sequence AC; Drug: Period 2 - Treatment Sequence AB; Drug: Period 2 - Treatment Sequence AC

• Registration Number: NCT02419001
• Lead Sponsor: Theriva Biologics, Inc.

Brief Summary

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.

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 Timeline

• Study Start: 2015-03
• Study First Submitted: 2015-04-01
• Study First Submitted QC: 2015-04-15
• Study First Posted: 2015-04-17
• Primary Completion: 2015-09
• Study Completion: 2015-10
• Results First Submitted: 2016-11-15
• Results First Submitted QC: 2016-11-15
• Results First Posted: 2017-01-11
• Status Verified: 2018-10
• Last Update Submitted: 2018-10-31
• Last Update Posted: 2018-11-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Period 1 - Treatment Sequence AB	Period 1 - Treatment Sequence AB	Treatment Sequence AB: * Period 1: Ceftriaxone 1 g infused IV over 30 minutes * \[Period 2: Ceftriaxone 1 g infused IV over 30 minutes and SYN-004 75 mg (1 x 75 mg capsule) orally administered 30 minutes before and 5.5 hours after the start of the ceftriaxone infusion\]
Period 1 - Treatment Sequence AC	Period 1 - Treatment Sequence AC	* Period 1: Ceftriaxone 1 g infused IV over 30 minutes * \[Period 2: Ceftriaxone 1 g infused IV over 30 minutes and SYN-004 150 mg (2 x 75 mg capsules) orally administered 30 minutes before and 5.5 hours after the start of the ceftriaxone infusion\]
Period 2 - Treatment Sequence AB	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
Period 2 - Treatment Sequence AC	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

Primary Outcome Measures

Name	Time	Method
Ceftriaxone PK Time to Reach Cmax (Tmax) With (Period 2) and Without (Period 1) SYN-004.	2 weeks	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.
Ceftriaxone PK Maximum Observed Plasma Concentration (Cmax) With (Period 2) and Without (Period 1) SYN-004.	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