Clinical trial NCT02419001: A Study to Evaluate the Effect of SYN-004 on the PK of IV Ceftriaxone in Adults With a Functioning Ileostomy
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Healthy Volunteers
Lead sponsor: Theriva Biologics, Inc.
Sponsor class: INDUSTRY
First posted: 2015-04-17
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Ceftriaxone PK Maximum Observed Plasma Concentration (Cmax) With (Period 2) and Without (Period 1) SYN-004.
timeFrame: 2 weeks
measure: Ceftriaxone PK Time to Reach Cmax (Tmax) With (Period 2) and Without (Period 1) SYN-004.
timeFrame: 2 weeks
measure: 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.
timeFrame: 2 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Columbus
country: United States
state: Ohio
city: Edmonton
country: Canada
state: Alberta
city: Montreal
country: Canada
Study officials:
affiliation: Synthetic Biologics
name: Michael Kaleko, M.D.
role: STUDY_CHAIR
References:
citation: 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.