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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
This is a Phase 1b/2a, randomized, multi-center, open-label study. Twenty otherwise healthy subjects with functioning ileostomies who are between the ages of 18 and 80 years, inclusive, will be enrolled. The entire duration of the study may be up to 63 days (from Screening to the end-of-study [EOS] visit).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SYN-004 | Drug |
| ||
| Esomeprazole |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Synthetic Biologics Investigative Site | Edmonton | Alberta | Canada | |||
| Synthetic Biologics Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28052855 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 150 mg SYN-004 | 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 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. SYN-004 Esomeprazole Ceftriaxone |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 |
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| Run-in Phase |
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| Treatment Period 2 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 150 mg SYN-004 | 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. SYN-004 Esomeprazole Ceftriaxone |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Ceftriaxone Concentration in Intestinal Chyme Period 1 | Ceftriaxone concentration in the presence of SYN-004 and the absence of esomeprazole. | Subjects with functioning illeostomies who received a single IV infusion of 1 g ceftriaxone. | Posted | Mean | Standard Error | ug/mL | 0-8.5 hours |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment Period 1 | In Treatment Period 1 (ceftriaxone + SYN-004), all 15 enrolled subjects received 1 g ceftriaxone and 14 received both 150 mg doses of SYN-004. One subject received only one 150 mg dose of SYN-004. In Treatment Period 1, one subject was discontinued from the study prior to receiving the second dose of SYN-004 due to a stoma site hemorrhage. The subject did not continue into the run-in phase or Treatment Period 2. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Discomfort | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michael Kaleko, M.D. | Synthetic Biologics Inc. | (240) 238-3862 | mkaleko@syntheticbiologics.com |
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| ID | Term |
|---|---|
| C000613271 | SYN-004 |
| D064098 | Esomeprazole |
| D002443 | Ceftriaxone |
| ID | Term |
|---|---|
| D009853 | Omeprazole |
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
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|
| Ceftriaxone | Drug |
|
| Montreal |
| Canada |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | Ribaxamase Concentration in Intestinal Chyme Period 1 | Concentrations of ribaximase (SYN-004) in intestinal chyme | Posted | Mean | Standard Error | ng/mL | 0-8.5 hours |
|
|
|
| Primary | Ceftriaxone Concentration in Intestinal Chyme Period 2 | Ceftriaxone concentration in the presence of SYN-004 and the absence of esomeprazole. | Subjects with functioning illeostomies who received a single IV infusion of 1 g ceftriaxone. | Posted | Mean | Standard Error | ug/mL | 0-8.5 hours |
|
|
|
| Primary | Ribaxamase Concentration in Intestinal Chyme Period 2 | Concentrations of ribaximase (SYN-004) in intestinal chyme | Posted | Mean | Standard Error | ng/mL | 0-8.5 hours |
|
|
|
| 0 |
| 15 |
| 0 |
| 15 |
| 3 |
| 15 |
| EG001 | Run-in Period | Treatment Periods 1 and 2 were separated by a 5- to 7-day run-in phase, during which subjects self-administered 40 mg of esomeprazole once daily in the morning. | 0 | 14 | 0 | 14 | 3 | 14 |
| EG002 | Treatment Period 2 | In Treatment Period 2, subjects received 2 oral doses of 150mg SYN-004 and 1g ceftriaxone in the presence of esomeprazole. In Treatment Period 2 (ceftriaxone + SYN-004 + esomeprazole), 14 subjects were exposed to ceftriaxone, SYN-004, and esomeprazole. One subject did not receive study drug according to protocol. | 0 | 14 | 0 | 14 | 2 | 14 |
| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Vessel puncture site bruise | General disorders | Systematic Assessment |
|
| Stoma site hemorrhage | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Postmenopausal hemorrhage | Reproductive system and breast disorders | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Hot flush | Vascular disorders | Systematic Assessment |
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Investigators do not see trial results ahead of public disclosure unless it is under CDA. Investigators will not be allowed to publish or disclose any study results prior to sponsor communicating it to the public.
| D009930 |
| Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D002439 | Cefotaxime |
| D002505 | Cephacetrile |
| D002511 | Cephalosporins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D013843 | Thiazines |
| Title | Measurements |
|---|---|
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