PMID- 38352727
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240215
IS  - 2590-1362 (Electronic)
IS  - 2590-1362 (Linking)
VI  - 17
DP  - 2024 Mar
TI  - Compatible co-administration of BioThrax(R) vaccine and ciprofloxacin-Results of a 
      randomized open-label drug-vaccine interaction trial.
PG  - 100431
LID - 10.1016/j.jvacx.2024.100431 [doi]
LID - 100431
AB  - The recommended treatment for post-exposure prophylaxis (PEP) following 
      known/suspected exposure to Bacillus anthracis involves immunization with anthrax 
      vaccine adsorbed (AVA, i.e., BioThrax(R) vaccine) and a course of antimicrobial 
      therapy. A drug-vaccine interaction clinical trial was conducted to determine 
      whether this combined treatment might modify antimicrobial exposure or vaccine 
      immunogenicity. A Phase 2, randomized, open-label, multi-center trial involving 
      154 healthy adult participants was completed to evaluate the effect of AVA 
      immunization (three doses administered subcutaneously (SC) at weeks 0, 2 and 4) 
      on the pharmacokinetics (PK) of ciprofloxacin, as well as the effect of 
      ciprofloxacin administration (500 mg po bid) on the immunogenicity of AVA. PK 
      parameters were derived using noncompartmental analysis of ciprofloxacin serum 
      concentrations. Immunogenicity was assessed using a toxin neutralizing antibody 
      (TNA) assay resulting in 50 % neutralization factor (NF(50)) values. Safety was 
      assessed via reports of adverse events (AEs), clinically significant changes in 
      laboratory parameters and vital signs, and collection of solicited local and 
      systemic reactogenicity reactions. Statistical analyses of the steady state (SS) 
      and single dose PK parameters C(max) and AUC(0--12h) indicated that the AVA PEP 
      regimen did not significantly modify ciprofloxacin exposure. Comparison of the 
      geometric mean TNA NF(50) values between participants receiving 
      AVA + ciprofloxacin and those receiving AVA alone showed that the combined 
      treatment was non-inferior to AVA alone. The trial met all prospectively defined 
      success criteria for the primary PK endpoint and for the secondary PK and 
      immunogenicity endpoints. There were no deaths, SAEs or AEs leading to drug 
      discontinuation or study withdrawal during the trial. Overall, concomitant 
      administration of ciprofloxacin and AVA produced no significant changes in the PK 
      profile of ciprofloxacin nor in the immunogenicity of AVA. Furthermore, this 
      trial demonstrated that the co-administration of ciprofloxacin and AVA was well 
      tolerated in healthy adult participants.
CI  - (c) 2024 The Author(s).
FAU - Cassie, David
AU  - Cassie D
AD  - Emergent BioSolutions Canada Inc., 155 Innovation Drive, Winnipeg, MB R3T 5Y3, 
      Canada.
FAU - Longstreth, Janice
AU  - Longstreth J
AD  - The Institute for Global Risk Research, LLC, 9119 Kirkdale Road, Suite 200, 
      Bethesda, MD 20817, USA.
FAU - Hopkins, Robert
AU  - Hopkins R
AD  - Adaptive Phage Therapeutics, 708 Quince Drive, Gaithersburg, MD 20878, USA.
FAU - Hunter-Stitt, Ericka
AU  - Hunter-Stitt E
AD  - Emergent BioSolutions Inc., 400 Professional Drive, Gaithersburg, MD 20879, USA.
FAU - Drobic, Bojan
AU  - Drobic B
AD  - Emergent BioSolutions Canada Inc., 155 Innovation Drive, Winnipeg, MB R3T 5Y3, 
      Canada.
FAU - Bellani, Melisa
AU  - Bellani M
AD  - Emergent BioSolutions Canada Inc., 155 Innovation Drive, Winnipeg, MB R3T 5Y3, 
      Canada.
LA  - eng
PT  - Journal Article
DEP - 20240107
PL  - England
TA  - Vaccine X
JT  - Vaccine: X
JID - 101748769
PMC - PMC10863310
OTO - NOTNLM
OT  - Anthrax
OT  - BioThrax(R)
OT  - Drug-vaccine interaction, ciprofloxacin
OT  - Post-exposure prophylaxis
OT  - Vaccine
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2024/02/14 06:43
MHDA- 2024/02/14 06:44
PMCR- 2024/01/07
CRDT- 2024/02/14 03:57
PHST- 2023/11/16 00:00 [received]
PHST- 2023/12/19 00:00 [revised]
PHST- 2024/01/04 00:00 [accepted]
PHST- 2024/02/14 06:44 [medline]
PHST- 2024/02/14 06:43 [pubmed]
PHST- 2024/02/14 03:57 [entrez]
PHST- 2024/01/07 00:00 [pmc-release]
AID - S2590-1362(24)00004-4 [pii]
AID - 100431 [pii]
AID - 10.1016/j.jvacx.2024.100431 [doi]
PST - epublish
SO  - Vaccine X. 2024 Jan 7;17:100431. doi: 10.1016/j.jvacx.2024.100431. eCollection 
      2024 Mar.