TABLE 2.
Summary of the population pharmacokinetic models used to guide ceftazidime-avibactam dosage regimen selection and validation in adultsa
| Population PK model (reference) | Clinical trials included | No. of subjects in population PK model dataset |
|---|---|---|
| Early population PK model (12) | Five phase 1 studies, one phase 2 study (cIAI) | Ceftazidime, 103; avibactam, 288 |
| Iteration 1b (13) | Ten phase 1 studies, two phase 2 studies (cIAI and cUTI) | Ceftazidime, 227; avibactam. 486 |
| Iteration 2 (14) | Studies included in iteration 1, and the following added studies: one phase 1 study, two phase 3 studies (RECLAIM, REPRISE first data-cutoff)c | Ceftazidime, 780; avibactam, 1,057 |
| Iteration 3 (15) | Studies included in iteration 2, final data from REPRISE and the following added studies: two phase 3 studies (RECAPTURE and RECLAIM 3) | Ceftazidime, 1,563; avibactam, 1,836 |
| Iteration 4 (16) | Studies included in iteration 3 and the REPROVE phase 3 study | Ceftazidime, 1,975; avibactam, 2,249 |
a
cIAI, complicated intra-abdominal infection; cUTI, complicated urinary tract infection; PK, pharmacokinetic.
b
The ceftazidime and avibactam population PK models in iteration 1 were built from the ground up using available clinical data and did not use the prior early population PK model as a basis for development.
c
The first data cutoff for REPRISE comprised 126 patients of the 333 patients eventually randomized.