CompletedNCT02419001Updated Nov 27, 2018Results posted

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

A Phase 1/2 interventional study of Period 1 - Treatment Sequence AB and Period 1 - Treatment Sequence AC in Healthy Volunteers, sponsored by Theriva Biologics, Inc.. Completed at 3 sites in 2 countries. Open to participants aged 18 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-11-27.

Sponsored by Theriva Biologics, Inc. · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 11
Allocation: Randomized
Ages: 18 Years to 70 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

Healthy Volunteers

Who can participate

Ages eligible: 18 Years to 70 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

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

Exclusion criteria

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 weeks prior to the screening visit.

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 11 participants (actual)

Study arms

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
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
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
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

Interventions

DrugPeriod 1 - Treatment Sequence AB
Period 1: Ceftriaxone 1 g infused IV over 30 minutes only, no SYN-004
DrugPeriod 1 - Treatment Sequence AC
Period 1: Ceftriaxone 1 g infused IV over 30 minutes only, no SYN-004
DrugPeriod 2 - Treatment Sequence AB
Period 2: Ceftriaxone 1 g infused IV over 30 minutes and SYN-004 75 mg
Also known as: ribaxamase
DrugPeriod 2 - Treatment Sequence AC
Period 2: Ceftriaxone 1 g infused IV over 30 minutes and SYN-004 150 mg
Also known as: ribaxamase

What researchers measure

Primary outcomes

Ceftriaxone PK Maximum Observed Plasma Concentration (Cmax) With (Period 2) and Without (Period 1) SYN-004.
Time frame: 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.
Time frame: 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.
Time frame: 2 weeks

Results

Posted Jan 11, 2017

Participant flow

Period 1- Ceftriaxone Without SYN-004

Participant flow — Period 1- Ceftriaxone Without SYN-004
Milestone	Low Dose	High Dose
Started	6	5
Completed	5	5
Not completed	1	0
Withdrew: Ae w/ ceftriaxone, not dosed w/ ip	1	0

Period 2- Ceftriaxone With SYN-004

Participant flow — Period 2- Ceftriaxone With SYN-004
Milestone	Low Dose	High Dose
Started	5	5
Completed	5	5
Not completed	0	0

Outcome measures

PrimaryCeftriaxone PK Maximum Observed Plasma Concentration (Cmax) With (Period 2) and Without (Period 1) SYN-004.

Time frame:: 2 weeks
Reported as:: Mean · ng/mL

Ceftriaxone PK Maximum Observed Plasma Concentration (Cmax) With (Period 2) and Without (Period 1) SYN-004.
ng/mL	Treatment Sequence AB	Treatment Sequence AC
Period 1	137,800.0 ± 10,709.8	178,600.0 ± 34,623.7
Period 2	143,800.0 ± 13,103.4	169,200.0 ± 32,782.6

PrimaryCeftriaxone 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.

Time frame:: 2 weeks
Reported as:: Mean · hours

Ceftriaxone PK Time to Reach Cmax (Tmax) With (Period 2) and Without (Period 1) SYN-004.
hours	Treatment Sequence AB	Treatment Sequence AC
Period 1	0.5 ± 0.0	0.5 ± 0.0
Period 2	0.5 ± 0.0	0.5 ± 0.0

PrimaryCeftriaxone 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.

Time frame:: 2 weeks
Reported as:: Mean · h*ng/mL

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.
h*ng/mL	Treatment Sequence AB	Treatment Sequence AC
Period 1	464,400.0 ± 26,884.9	656,200.0 ± 105,257.8
Period 2	478,800.0 ± 37,117.4	643,800.0 ± 108,349.9

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Low Dose	—	0/6 (0%)	4/6 (66.7%)
High Dose	—	0/5 (0%)	4/5 (80%)

Most frequent other events

Showing 10 of 17

Most frequent other events
Event	Low Dose	High Dose
HeadacheNervous system disorders	1/6	2/5
PollakiuriaRenal and urinary disorders	0/6	1/5
Back painMusculoskeletal and connective tissue disorders	0/6	1/5
Pain in extremityMusculoskeletal and connective tissue disorders	0/6	1/5
Upper respiratory tract infectionInfections and infestations	0/6	1/5
ErythemaSkin and subcutaneous tissue disorders	0/6	1/5
Abdominal painGastrointestinal disorders	1/6	0/5
SomnolenceNervous system disorders	1/6	0/5
Catheter site bruiseGeneral disorders	1/6	0/5
DiscomfortGeneral disorders	1/6	0/5

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Low Dose	High Dose	Total
Mean	41.3 ± 11.9	57.1 ± 11.6	48.5 ± 13.8

Sex: Female, Male
Sex: Female, Male(Participants)	Low Dose	High Dose	Total
Female	1	2	3
Male	5	3	8

Study locations

3 sites

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

References and documents

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. PubMed 28052855 ↗

Registry details

Key details

Study ID: NCT02419001
Lead sponsor: Theriva Biologics, Inc.
Responsible party: Sponsor
First posted: Apr 17, 2015
Start date: Mar 2015
Primary completion: Sep 2015
Completion: Oct 2015
Results posted: Jan 11, 2017
Last update: Nov 27, 2018

Study contacts

Michael Kaleko, M.D.

study chair · Synthetic Biologics

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Oct 2018. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies from this sponsor

Theriva Biologics, Inc.

Start the discussion