The goals of this study are to evaluate the safety and tolerability of multiple ascending doses of PF-04634817 administered orally to healthy adult subjects. In additional, the plasma and urinary pharmacokinetics of multiple ascending doses of PF-04634817 administered orally to healthy adult subjects will be evaluated. Finally, the effect of multiple doses of PF-04634817 on circulating monocytes will be explored.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
48
Oral solution of PF-04634817 at 3 mg will be given once daily for 14 days.
Oral solution of PF-04634817 at 3 mg will be given once daily for 14 days.
Oral solution of PF-04634817 at 30 mg will be given once daily for 14 days.
Pfizer Investigational Site
New Haven, Connecticut, United States
Adverse events, supine and standing vital sign measurements, 12-lead ECGs, blood and urine safety tests.
Time frame: 14 days
Plasma PK Day 1: Cmax, Tmax, AUClast, AUCtau at all dose levels. Plasma PK Day 14: Cmax, Tmax, AUClast, AUCtau, AUCinf, t½, CL/F and Vss/F at all dose levels.
Time frame: 14 days
AUCtau (Day 14) vs. AUCtau (Day 1) - estimate of accumulation ratio; Cmax (Day 14) vs. Cmax (Day 1); Tmax (Day 14) vs. Tmax (Day 1).
Time frame: 14 days
Urinary PK: Aet (amount excreted in urine); Aet% at all doses of PF-04634817 where t = 24 hours on Day 1 and 14; CLr at all doses on Day 14.
Time frame: 14 days
Pharmacodynamic: MCP-1 change from baseline.
Time frame: 14 days
Pharmacodynamic: p-ERK Inhibition in human monocytes: percent inhibition of monocyte p-ERK activity relative to the pre-dose baseline value
Time frame: 14 days
MIP-1β stimulated CCR5 receptor internalization: percent inhibition of internalization relative to the pre-dose baseline value
Time frame: 14 days
Absolute and percent change in circulating monocytes; Absolute and percent change in CD14+CD16+ monocytes.
Time frame: 14 days
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Oral solution of PF-04634817 at 100 mg will be given once daily for 14 days.
Oral solution of PF-04634817 at 300 mg will be given once daily for 14 days.
Cohort will only be dosed if necessary. Dose selected for this cohort may be a repeat of a previous cohort or intermediate dose not to exceed 300 mg.