
Methods:
This study is a randomized, double blinded (investigator and subject blinded, sponsor-open), placebo-controlled, multiple dose study in healthy volunteers of PF-03709270, with or without co-administration of probenecid, in fed or fasted state. Subjects were dosed twice a day for 6 days and once on Day 7. For the treatment groups dosed in the fed state, subjects were dosed approximately 30 minutes after the start of their meal. Pharmacokinetic sampling was done in 8 subjects per treatment group.
Results:
Treatment |
Fed / Fasted |
Descriptive Statistic |
Parameter (Day 1) |
|||
Cmax (ng/mL) |
AUCTAU (hr*ng/mL) |
T>MIC (0.5µg/ml) [hr] |
T> MIC (0.5 µg/ml) [%] |
|||
500 mg PF-03709270 |
Fasted |
Mean |
1770.000 |
3683.093 |
2.660 |
22.2 |
SD |
529.474 |
728.892 |
|
|
||
Median |
1720.00 |
3478.43 |
|
|
||
CV% |
29.9 |
19.8 |
15.0 |
|
||
500 mg PF-03709270 |
Fed |
Mean |
1869.875 |
4545.342 |
3.127 |
26.1 |
SD |
741.019 |
1131.901 |
|
|
||
Median |
1725.00 |
4509.96 |
|
|
||
CV% |
39.6 |
24.9 |
27.9 |
|
||
500 mg PF-03709270 + 500 mg probenecid |
Fasted |
Mean |
1773.750 |
3952.865 |
3.063 |
25.5 |
SD |
465.463 |
893.698 |
|
|
||
Median |
1830.00 |
4238.98 |
|
|
||
CV% |
26.2 |
22.6 |
23.2 |
|
||
500 mg PF-03709270 + 500 mg probenecid |
Fed |
Mean |
1690.000 |
6396.538 |
5.364 |
44.7 |
SD |
576.517 |
1415.977 |
|
|
||
Median |
1500.00 |
6301.46 |
|
|
||
CV% |
34.1 |
22.1 |
41.9 |
|
Conclusion: Both food and probenecid increase the absorption of PF-03709270 and consequently serum levels of sulopenem. The combination of food and probenecid further increases serum exposures of sulopenem. Probenecid, food, or the combination of both, all significantly prolong the T>MIC for sulopenem. These data will help inform PKPD modelling in selection of a dose for Phase 3 studies.

M. Dunne,
Iterum Therapeutics:
Employee
and
Shareholder
,
Salary
S. Puttagunta, Iterum Therapeu: Employee and Shareholder , Salary
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