Trial reportClinical drug investigation2016
Tolerability and Pharmacokinetics of SYN-004, an Orally Administered β-Lactamase for the Prevention of Clostridium difficile-Associated Disease and Antibiotic-Associated Diarrhea, in Two Phase 1 Studies.
Trial report in Clinical drug investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 30 citations in OpenAlex.
- The Oral β-Lactamase SYN-004 (Ribaxamase) Degrades Ceftriaxone Excreted into the Intestine in Phase 2a Clinical Studies.Antimicrobial agents and chemotherapy · 2017Trial
- Review
- The role of the microbiota in the management of intensive care patients.Annals of intensive care · 2022Review
- Hospital Infection Control:Clinics in colon and rectal surgery · 2020Review
- Carbapenem-Resistant Enterobacteriaceae in Solid Organ Transplantation: Management Principles.Current infectious disease reports · 2019Review
- Factors related to antibiotic-associated diarrhea in patients in the intensive care unit receiving antifungals: a single-center retrospective study.The Journal of international medical research · 2019Article
- Oral Metallo-Beta-Lactamase Protects the Gut Microbiome From Carbapenem-Mediated Damage and Reduces Propagation of Antibiotic Resistance in Pigs.Frontiers in microbiology · 2019Article
- Novel therapies and preventative strategies for primary and recurrent Clostridium difficile infections.Annals of the New York Academy of Sciences · 2019Review
- Combined administration of antibiotics increases the incidence of antibiotic-associated diarrhea in critically ill patients.Infection and drug resistance · 2019Article
- Low dose oral beta-lactamase protects the gut microbiome from oral beta-lactam-mediated damage in dogs.AIMS public health · 2019Article
- Enzyme Inhibitor Antibiotics and Antibiotic-Associated Diarrhea in Critically Ill Patients.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Risk Factors for Antibiotic-Associated Diarrhea in Critically Ill Patients.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- A Review of Experimental and Off-Label Therapies for Clostridium difficile Infection.Infectious diseases and therapy · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSYN-004 is an orally administered β-lactamase enzyme, designed to be given concurrently with certain intravenous β-lactam antibiotics like cephalosporins. SYN-004 is intended to degrade residual antibiotics excreted into the intestine as a result of hepatobiliary excretion and to prevent the disruption of the gut microbiome by these excess antibiotics. Preserving the gut microbiome is expected to prevent secondary infections by pathogens like Clostridium difficile and protect against other antibiotic-associated diarrheas.
methodsTwo, randomized, double blind, placebo-controlled Phase 1 clinical studies were conducted in normal healthy adult volunteers to assess the tolerability and systemic absorption of single and multiple doses of SYN-004. A single-ascending dose study investigated single oral doses of 75-750 mg SYN-004 and was conducted in 40 subjects (five cohorts of six active and two placebo subjects). A multiple-ascending dose study investigated doses of 75-300 mg SYN-004, administered every 6 h for 7 days and was conducted in 24 subjects (three cohorts of six active and two placebo subjects). The safety and tolerability of SYN-004 was assessed and serial plasma and serum samples were collected to assess the pharmacokinetics and potential immunogenicity of SYN-004.
resultsMinimal and mild adverse events were reported in ~30 % of the subjects who received active drug and placebo and no antidrug antibodies were detected in any subject. Analysis of serial plasma samples demonstrated negligible systemic bioavailability of SYN-004 with most plasma concentrations being below the lower limit of quantitation (0.8 ng/mL) for the assay. SYN-004 was well tolerated in the 48 subjects who received active drug, and adverse events in those subjects were comparable to the 16 subjects who received placebo, up to the maximum doses administered in each study.
conclusionSYN-004 was well tolerated up to a single oral dose of 750 mg and multiple doses of 300 mg every 6 h for 7 days. The pharmacokinetic results support that SYN-004 remained localized in the intestine.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.