Cadazolid
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Cadazolid (formerly ACT-179811) is a nonabsorbable, fluoroquinolone-oxazolidinone class antibiotic that inhibits bacterial protein synthesis. The substance is moderately lipophilic (log D = 1.2), acidic (pKa = 6.0), and poorly soluble in aqueous solution (150 ng/ml). Its chemical structure is formally [(R)-1-cyclopropyl-6-fluoro-7-{4-[2-fluoro-4-(5-hydroxymethyl-2-oxo-oxazolidin-3-yl)-phenoxymethyl]-4-hydroxy-piperidin-1-yl}-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid], and the molecular formula is C29H29N3O8F2 (Baldoni et al, 2014) (Figure 74.1).
Emerging drugs for the treatment of clostridium difficile
Published in Expert Opinion on Emerging Drugs, 2019
Giovanni Cammarota, Antonella Gallo, Gianluca Ianiro, Massimo Montalto
Phase-III studies are ongoing for cadazolid and results are still not available. Cadazolid, developed by Actelion, is a novel oxazolidinone, with a potent antimicrobial activity against C. difficile and spore formation in vitro, although the exact mechanism of action is not yet fully elucidated [54]. A phase-II study [58] showed lower recurrence rates and higher sustained clinical response in CDI patients when treated with cadazolid (ad doses of 250, 500 or 1,000 mg twice daily) vs. vancomycin treatment (at doses of 125 mg four times daily). Results were independently from different dosages of cadazolid.
Clinical review of Clostridium difficile infection: an update on treatment and prevention
Published in Expert Opinion on Pharmacotherapy, 2018
Lindsay M. Daniels, Wesley D. Kufel
Cadazolid is a poorly absorbed oxazolidinone antibiotic that works by inhibiting bacterial protein synthesis. Two phase 3 studies (NCT01983683 and NCT01987895) compared the safety and efficacy of cadazolid to vancomycin. These trials evaluated non-inferiority for clinical cure as the primary outcome and superiority for sustained cure as the secondary outcome. Results for these trials are currently available on clinicaltrials.gov. In one of these trials (NCT01983683), cadazolid did not meet criteria for non-inferiority for the primary end point or superiority for the secondary end point. Currently, development for cadazolid has been discontinued.
Investigational drug therapies currently in early-stage clinical development for the treatment of clostridioides (clostridium) difficile infection
Published in Expert Opinion on Investigational Drugs, 2019
Mai-Chi N. Tran, Ravina Kullar, Ellie J. C. Goldstein
Cadazolid (ACT-179,811) is a non-absorbable, narrow spectrum agent comprise an oxazolidinone pharmacophore with a substituted fluoroquinolone moiety [89,90]. The oxazolidinone moiety inhibited protein synthesis and the fluoroquinolone inhibited DNA synthesis. It was noted to be highly active against C. difficile both in vitro and in animal models and showed biological effects on both C. difficile toxin production and spore formation [91]. A Phase 2 multicenter, randomized, dose ranging, control trial of three different doses of cadazolid compared with vancomycin enrolled 84 patients and did not meet its endpoint due to rigid definitions of diarrhea and cure. Resolution of diarrhea was defined as ≤2 semi-formed or formed stools and no liquid or unformed stools for two consecutive 24-h periods and neither cadazolid nor the vancomycin comparator reached the primary endpoint [92,93]. However, this antibiotic was moved into Phase 3 because of demonstrated superiority to vancomycin for recurrence and sustained clinical cure. Two Phase 3 trials (IMPACT I and II, NCT01987895 and NCT01983683) that compared the efficacy of cadazolid 250 mg twice daily to vancomycin 125 mg four times daily also failed their endpoints. These studies developed a new patient-reported outcome questionnaire for symptoms of CDI as well as an Investigator’s assessment of clinical response (ICR) rate and sustained response rate (ISR Rate). Results have yet to be published, but after Actelion was acquired by Johnson and Johnson, that company noted that in two trials designed to be identical, cadazolid chalked up one success and one failure, after which they discontinued current development as it was uncertain if cadazolid as effective as vancomycin [94].
Related Knowledge Centers
- Antibiotic
- Chemical Structure
- Clinical Trial
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- Metronidazole
- Pharmacophore
- Diarrhea
- Vancomycin
- 2-Oxazolidone
- Clostridioides Difficile