- |||||||||| PK/PD data, Review, Journal: Multidrug-resistant Acinetobacter baumannii infections: current evidence on treatment options and role of PK/PD in dose optimization. (Pubmed Central) - Sep 4, 2019
Novel agents such as cefiderocol, plazomicin, eravacycline, and sulbactam/ETX2514 combination are promising options for the treatment of different infection pathologies caused by MDR A. baumannii, but these have yet to be evaluated in randomized controlled trials. A better understanding of the pharmacokinetics (PK)/pharmacodynamics (PD) of the "old" antibiotics is required to optimize their dosing regimens to maximize bacterial killing, minimize toxicities and improve clinical outcomes.
- |||||||||| Vabomere (meropenem/vaborbactam) / Cempra, Xerava (eravacycline) / Tetraphase
Novel Therapeutic Options for the Treatment of Multi-Drug Resistant Achromobacter Respiratory Infections () - Aug 26, 2019 - Abstract #IDWeek2019IDWeek_2687; Inpatient all-cause mortality was 11%.Conclusion : Antibiotics available to treat MDR Achromobacter infections are limited and lack standard susceptbility breakpoint recommendations. Based on this evaluation, novel agents, such as eravacycline or meropenem/vaborbactam, may be viable treatment options for patients with MDR Achromobacter respiratory infections.
- |||||||||| Nuzyra (omadacycline) / Paratek, Xerava (eravacycline) / Tetraphase
Assessment of Translational In Vitro and Animal Pharmacokinetic-Pharmacodynamic Data Used to Support Drug Development of Recent Tetracycline Derivatives () - Aug 26, 2019 - Abstract #IDWeek2019IDWeek_2136; Higher values of the MIC cutoff signify that the drug can treat larger proportions of the bacterial population; therefore, high clinical to nonclinical MIC cutoff ratios signify that the drugs had more activity in reducing the bacterial population in clinical than in nonclinical studies.Conclusion : Thus, the nonclinical models for ERV and OMD under-predicted microbiological response and breakpoints. While nonclinical models are generally useful, more characterization of translational factors may be needed to allow nonclinical models to be more predictive of clinical trial outcomes.
- |||||||||| Xerava (eravacycline) / Tetraphase
Activity of Eravacycline Against Contemporary Gram-negative Clinical Isolates from New York City Hospitals () - Aug 26, 2019 - Abstract #IDWeek2019IDWeek_1461; Clinicians should be aware of the nuances of ERV susceptibility testing and recognize that the modal distribution of ERV MICs against CRE lies on either side of the susceptibility breakpoint. ERV possesses significant in vitro activity against contemporary clinical isolates of Enterobacteriaceae and A. baumannii from NYC, including many carbapenemase producing strains.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono, paclitaxel / Generic Mfg., Opdivo (nivolumab) / Ono Pharma, BMS
Review, Journal: Systemic Therapies for Advanced Squamous Cell Anal Cancer. (Pubmed Central) - Aug 23, 2019 Other cytotoxic agents, especially docetaxel and paclitaxel, have shown activity in both the chemotherapy-naive and chemo-refractory setting and are currently being investigated in clinical trials. Finally, further to the promising results of early clinical trials, immunotherapy with checkpoint inhibitors (i.e. nivolumab and pembrolizumab) is likely to become a standard second-line treatment option.
- |||||||||| Comtan (entacapone) / Novartis, Orion, tolcapone (CRX-1008) / Corino Therap, SOM Biotech, Tasmar (tolcapone) / Endo, Bausch Health
Journal: Effect of the catechol-O-methyltransferase inhibitors tolcapone and entacapone on fatty acid metabolism in HepaRG cells. (Pubmed Central) - Jul 28, 2019 Tolcapone increased mRNA expression of fatty acid transporters, inhibited activation of long-chain fatty acids and impaired VLDL secretion, causing hepatocellular triglyceride accumulation. The findings may be relevant in patients with a high tolcapone exposure and preexisting mitochondrial dysfunction.
- |||||||||| Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
Trial completion date, Trial primary completion date: A Safety and PK Study of IV Eravacycline (clinicaltrials.gov) - Jul 22, 2019 P1, N=20, Recruiting, The findings may be relevant in patients with a high tolcapone exposure and preexisting mitochondrial dysfunction. Trial completion date: Oct 2019 --> Nov 2020 | Trial primary completion date: Jun 2019 --> Aug 2020
- |||||||||| Journal: New antibiotics for ventilator-associated pneumonia. (Pubmed Central) - Jul 19, 2019
Newly approved and investigational drugs for the treatment of VAP are expected to offer many advantages for the management of patients with respiratory infections caused by MDR. Promising characteristics of new compounds include high activity against both methicillin-resistant Staphylococcus aureus and MDR Gram-negative bacteria and a favorable safety profile.
- |||||||||| Flagyl (metronidazole) / SLA
Journal: Substrate selectivity of human aldehyde oxidase 1 in reduction of nitroaromatic drugs. (Pubmed Central) - Jul 6, 2019 ...Recently, we found that AOX1 catalyzed the reduction of drugs such as nitrazepam and dantrolene...We found that clonazepam, flunitrazepam, flutamide, nilutamide, nimesulide, and nimetazepam were substantially reduced by recombinant AOX1 and HLC, whereas azelnidipine, nifedipine, and nimodipine were slightly reduced and metronidazole and tolcapone were not reduced...Inhibition studies using known AOX1 inhibitors supported the role of AOX1 in the reduction of drugs in HLC. In conclusion, this provides new information related to the substrate selectivity of human AOX1 for the reduction of nitroaromatic drugs.
- |||||||||| Review, Journal: The "Old" and the "New" Antibiotics for MDR Gram-Negative Pathogens: For Whom, When, and How. (Pubmed Central) - Jun 28, 2019
Eravacycline holds promise in the treatment of infections by CRAB, with a broad spectrum of activity similar to tigecycline, and improved pharmacokinetics...Finally, fosfomycin as part of combination treatment for CRE infections and P. aeruginosa, deserves a greater attention. Optimal conditions for monotherapy and the "when and how" of combination treatments integrating the novel agents will be discussed.
- |||||||||| Xerava (eravacycline) / Tetraphase
Clinical, Journal: Evaluation of theactivity of eravacycline against a broad spectrum of recent clinical anaerobic isolates. (Pubmed Central) - Jun 22, 2019 Eravacycline and 11 comparator antibiotics were tested against recent anaerobic clinical isolates, including MDRspp. andEravacycline was potentagainst all the isolates tested, including strains with tetracycline-specific resistance determinants and MDR anaerobic pathogens resistant to carbapenems and/or β-lactam/β-lactamase inhibitor combinations.
- |||||||||| Xerava (eravacycline) / Tetraphase
Retrospective data, Review, Journal: The Efficacy and Safety of Eravacycline in the Treatment of Complicated Intra-Abdominal Infections: A Systemic Review and Meta-Analysis of Randomized Controlled Trials. (Pubmed Central) - Jun 21, 2019 Although eravacycline was associated with higher risk of treatment-emergent adverse event than comparators (RR, 1.34; 95% CI, 1.13-1.58; I = 0%), no significant differences were found between eravacycline and comparators for the risk of serious adverse event (RR, 1.04; 95% CI, 0.65-1.65; I = 0%), discontinuation of study drug because of adverse event (RR, 0.68; 95% CI, 0.23-1.99; I = 13%), and all-cause mortality (RR, 1.09; 95% CI, 0.41-2.9; I = 28%). In conclusion, the clinical efficacy of eravacycline is as high as that of the comparator drugs in the treatment of cIAIs and this antibiotic is as well tolerated as the comparators.
- |||||||||| prexasertib (ACR-368) / Acrivon Therap
Enrollment change, Trial completion date, Trial termination, Trial primary completion date, Combination therapy: Prexasertib in Combination With MEC in Relapsed/Refractory AML and High Risk MDS - a Phase I Trial (clinicaltrials.gov) - Jun 12, 2019 P1, N=2, Terminated, Active, not recruiting --> Completed N=28 --> 2 | Trial completion date: Jun 2021 --> Mar 2019 | Recruiting --> Terminated | Trial primary completion date: Jul 2020 --> Mar 2019; Sponsor Decision
- |||||||||| Review, Journal: Infections by multidrug-resistant Gram-negative Bacteria: what's new in our arsenal and what's in the pipeline? (Pubmed Central) - Jun 9, 2019
This vulnerability, along with strategies to tackle antimicrobial resistance development, prompts the development of new antibiotic agents as well as exploration of alternative treatment options. This article summarises the new antibiotics that have recently been approved for Gram-negative bacterial infections, looks down the pipeline at promising agents currently in phase I, II, or III clinical trials, and introduces new alternative avenues that show potential in combating multidrug-resistant Gram-negative bacteria.
- |||||||||| Comtan (entacapone) / Novartis, Orion
PK/PD data, Journal: Pharmacodynamic Evaluation of novel Catechol-O-methyltransferase Inhibitors. (Pubmed Central) - Jun 6, 2019 The cytotoxicity of tolcapone and CNCAPE in human neuroblastoma SK-N-SH cells and human liver adenocarcinoma SK-HEP-1 cells was also assessed. At lower concentrations, CNCAPE did not reduce cell viability, suggesting that CNCAPE may have a potential therapeutic role as a centrally active COMT inhibitor.
- |||||||||| Review, Journal: Treatment of Infections Due to MDR Gram-Negative Bacteria. (Pubmed Central) - May 2, 2019
Despite important progresses, pharmacokinetic/pharmacodynamic optimization of dosages and treatment duration in critically ill patients has still some areas of uncertainty requiring further study, that should take into account also resistance selection as a major endpoint. Treatment of severe MDR-GNB infections in critically ill patients in the near future will require an expert and complex clinical reasoning, of course taking into account the peculiar characteristics of the target population, but also the need for adequate empirical coverage and the more and more specific enzyme-level activity of novel antimicrobials with respect to the different resistance mechanisms of MDR-GNB.
- |||||||||| tolcapone (CRX-1008) / Corino Therap, SOM Biotech
Enrollment closed: Short-term Effects of TOLCAPONE on Transthyretin Stability in Subjects With Leptomeningeal TTR Amyloidosis (ATTR) (clinicaltrials.gov) - May 1, 2019 P1, N=10, Active, not recruiting, Treatment of severe MDR-GNB infections in critically ill patients in the near future will require an expert and complex clinical reasoning, of course taking into account the peculiar characteristics of the target population, but also the need for adequate empirical coverage and the more and more specific enzyme-level activity of novel antimicrobials with respect to the different resistance mechanisms of MDR-GNB. Recruiting --> Active, not recruiting
- |||||||||| tolcapone (CRX-1008) / Corino Therap, SOM Biotech, Tasmar (tolcapone) / Endo, Bausch Health
Preclinical, Journal: COMT Inhibition Alters Cue-Evoked Oscillatory Dynamics during Alcohol Drinking in the Rat. (Pubmed Central) - Apr 20, 2019 These results suggest a link between corticostriatal synchrony and genetic risk for excessive drinking. Moreover, inhibition of COMT within these systems may result in reduced attribution of salience to reward paired stimuli via modulation of stimulus-evoked changes to cortical oscillations in genetically susceptible populations.
- |||||||||| prexasertib (ACR-368) / Acrivon Therap
Trial completion date, Trial primary completion date, BRCA Biomarker, Metastases: A Phase II Single Arm Pilot Study of the Chk1/2 Inhibitor (LY2606368) in BRCA1/2 Mutation Associated Breast or Ovarian Cancer, Triple Negative Breast Cancer, High Grade Serous Ovarian Cancer, and Metastatic Castrate-Resistant Prostate Cancer (clinicaltrials.gov) - Apr 19, 2019 P2, N=153, Recruiting, Moreover, inhibition of COMT within these systems may result in reduced attribution of salience to reward paired stimuli via modulation of stimulus-evoked changes to cortical oscillations in genetically susceptible populations. Trial completion date: Jun 2020 --> Dec 2020 | Trial primary completion date: Jun 2019 --> Jun 2020
- |||||||||| Xerava (eravacycline) / Tetraphase, SOM Biotech, Ewha Womans University
Surveillance of the in vitro activity of eravacycline and comparators against clinical isolates from Europe during 2017 () - Apr 5, 2019 - Abstract #ECCMID2019ECCMID_2269; Trial completion date: Jun 2020 --> Dec 2020 | Trial primary completion date: Jun 2019 --> Jun 2020 Overall, eravacycline exhibited excellent in vitro activity against the vast majority of Enterobacteriaceae, including isolates that produced ESBL and was 2-4 fold more active than tigecycline Against A baumannii, eravacycline was at least 8 fold more active than tigecycline.
- |||||||||| bevantolol (SOM3355) / SOM Biotech
Enrollment closed, Trial completion date, Trial primary completion date: Efficacy and Safety of SOM3355 in Huntington's Disease Chorea (clinicaltrials.gov) - Mar 18, 2019 P2a, N=30, Active, not recruiting, Based on this data, minocycline is the lead agent for further studies and should be considered for S. maltophilia infections, including those resistant to levofloxacin and/or sulfamethoxazole-trimethoprim. Recruiting --> Active, not recruiting | Trial completion date: Jun 2019 --> Sep 2019 | Trial primary completion date: Apr 2019 --> Aug 2019
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