Effect of Co-administration of the anthrax vaccine adsorbed, adjuvanted with ciprofloxacin or doxycycline on antibiotic pharmacokinetics and the vaccine immunogenicity: A phase 2 drug-vaccine interaction study
Bibliographic record
Abstract
CYFENDUS® vaccine (Anthrax Vaccine Adsorbed, Adjuvanted) with the recommended antibacterial drugs is licensed for post-exposure prophylaxis (PEP) following suspected or confirmed Bacillus anthracis exposure. This pre-licensure study examined potential interaction of CYFENDUS vaccine with ciprofloxacin and doxycycline when administered concomitantly. In this Phase 2, open-label study, healthy adult participants (18 to 45 years of age; n = 210) were randomized to receive either ciprofloxacin+CYFENDUS vaccine, doxycycline+CYFENDUS vaccine, or CYFENDUS vaccine only. Pharmacokinetic (PK) parameters of antibacterials such as steady-state maximum concentration (C max ) and area under the curve from 0 to 12 h (AUC 0-12h ) were assessed. Immunogenicity of the vaccine was evaluated using 50 % neutralizing factor (NF 50 ) values generated by toxin neutralizing antibody (TNA) assay. Solicited reactogenicity and adverse events (AEs) were collected for safety evaluation. The PK endpoint was met for ciprofloxacin. The vaccine had no effect on PK with 90 % confidence intervals (CIs) of the mean ratios for AUC 0-12h [90 % CI: 0.8895,1.0718] and C max [90 % CI: 0.8693,1.0838] contained within the predefined equivalence criteria [0.80, 1.25]. The PK endpoint was not met for doxycycline, wherein the 90 % of the mean ratios for AUC 0-12h [90 % CI: 0.8187,1.0278] was within the equivalence criteria, but the lower bound of the 90 % CI for C max [90 % CI: 0.7841,1.0271] was below the equivalence limits [0.80, 1.25]; this impact on C max may be negligible to the extent that doxycycline efficacy is correlated with AUC. The immunogenicity endpoint was met, wherein the lower bound 95 % CIs for geometric mean ratio of TNA NF 50 for the vaccine with ciprofloxacin (0.78) or doxycycline (0.81) to vaccine alone were above the non-inferiority margin (0.5). Most solicited reactogenicities and AEs were Grade 1 or 2 in severity. CYFENDUS vaccination with or without ciprofloxacin or doxycycline had an acceptable safety profile and co-administration did not affect the relevant PK and immunogenicity parameters. ClinicalTrials.gov Identifier: NCT04067011
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".