Analysis of Pooled Phase 3 Safety Data for Delafloxacin in Acute Bacterial Skin and Skin Structure Infections.
Acute Disease
Administration, Intravenous
Administration, Oral
Aged
Aged, 80 and over
Anti-Bacterial Agents
/ pharmacology
Drug Therapy, Combination
Female
Fluoroquinolones
/ pharmacology
Humans
Incidence
Male
Middle Aged
Skin Diseases, Bacterial
/ drug therapy
Soft Tissue Infections
/ drug therapy
Treatment Outcome
ABSSSI
delafloxacin
fluoroquinolone
safety
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
08 04 2019
08 04 2019
Historique:
entrez:
9
4
2019
pubmed:
9
4
2019
medline:
1
7
2020
Statut:
ppublish
Résumé
Through improved understanding of the structure-activity relationship attributes of fluoroquinolones, molecule development has improved efficacy, safety, and tolerability of the class. Adverse events (AEs) associated with the fluoroquinolones are well defined and a prospective part of the development process. However, not all fluoroquinolones have the same AE profile with different substitutions on the core molecule resulting in differences in side effects and spectrum of activity. Unique structural attributes of delafloxacin (DLX) may differentiate its AE profile compared to other fluoroquinolones. This analysis compared the incidence of AEs between DLX and vancomycin/aztreonam across two phase 3 ABSSSI studies in order to provide a broader overview of DLX safety. Safety events occurring in all subjects in the pivotal phase 3 trials were pooled to provide a broad overview of DLX safety. DLX was safe and well-tolerated in the pooled phase 3 ABSSSI trial population of 741 subjects. Treatment-emergent AEs (TEAEs) were seen in the DLX group versus the comparator group at 45.1% and 47.7%, respectively. Most were mild or moderate in severity. Treatment-related TEAEs were reported in the DLX group versus the comparator group at rates of 22.1% and 26.1%, respectively. Available data show DLX is well tolerated in both intravenous and oral formulation for the treatment of ABSSSI and does not appear to be associated with increased risk of AEs associated with other fluoroquinolones. It remains important to monitor for potential AEs that have been observed with other fluoroquinolones.
Sections du résumé
BACKGROUND
Through improved understanding of the structure-activity relationship attributes of fluoroquinolones, molecule development has improved efficacy, safety, and tolerability of the class. Adverse events (AEs) associated with the fluoroquinolones are well defined and a prospective part of the development process. However, not all fluoroquinolones have the same AE profile with different substitutions on the core molecule resulting in differences in side effects and spectrum of activity. Unique structural attributes of delafloxacin (DLX) may differentiate its AE profile compared to other fluoroquinolones. This analysis compared the incidence of AEs between DLX and vancomycin/aztreonam across two phase 3 ABSSSI studies in order to provide a broader overview of DLX safety.
METHODS
Safety events occurring in all subjects in the pivotal phase 3 trials were pooled to provide a broad overview of DLX safety.
RESULTS
DLX was safe and well-tolerated in the pooled phase 3 ABSSSI trial population of 741 subjects. Treatment-emergent AEs (TEAEs) were seen in the DLX group versus the comparator group at 45.1% and 47.7%, respectively. Most were mild or moderate in severity. Treatment-related TEAEs were reported in the DLX group versus the comparator group at rates of 22.1% and 26.1%, respectively.
CONCLUSIONS
Available data show DLX is well tolerated in both intravenous and oral formulation for the treatment of ABSSSI and does not appear to be associated with increased risk of AEs associated with other fluoroquinolones. It remains important to monitor for potential AEs that have been observed with other fluoroquinolones.
Identifiants
pubmed: 30957169
pii: 5428810
doi: 10.1093/cid/ciy1080
pmc: PMC6451993
doi:
Substances chimiques
Anti-Bacterial Agents
0
Fluoroquinolones
0
delafloxacin
6315412YVF
Types de publication
Clinical Trial, Phase III
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
S233-S240Informations de copyright
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.
Références
Clin Ther. 2016 Jan 1;38(1):53-65
pubmed: 26718605
Expert Opin Drug Metab Toxicol. 2015 Jan;11(1):25-39
pubmed: 25423877
Int J Infect Dis. 2015 Jan;30:67-73
pubmed: 25448332
Clin Infect Dis. 2005 Jul 15;41 Suppl 2:S144-57
pubmed: 15942881
Clin Infect Dis. 2001 Sep 15;33 Suppl 3:S180-6
pubmed: 11524717
Open Forum Infect Dis. 2018 Sep 10;5(10):ofy220
pubmed: 30349845
Curr Med Chem. 2001 Mar;8(4):371-84
pubmed: 11172695
J Antimicrob Chemother. 2016 Mar;71(3):821-9
pubmed: 26679243
Clin Infect Dis. 2018 Aug 16;67(5):657-666
pubmed: 29518178
Antimicrob Agents Chemother. 2004 Mar;48(3):799-803
pubmed: 14982767
Photochem Photobiol Sci. 2018 Jun 13;17(6):773-780
pubmed: 29721574
Clin Ther. 2017 Jun;39(6):1182-1190
pubmed: 28495029
J Antimicrob Chemother. 2017 Dec 1;72(12):3471-3480
pubmed: 29029278
Future Microbiol. 2015;10(7):1111-23
pubmed: 26119479
Am J Med. 2005 Mar;118(3):259-68
pubmed: 15745724
Expert Opin Drug Metab Toxicol. 2017 Nov;13(11):1193-1200
pubmed: 28988505