Abstract
AIMS
The objectives of this phase 1 study were to confirm the tolerability of single
ascending subcutaneous doses of PP 1420 in healthy subjects, to assess its
adverse effects and to investigate the drug’s pharmacokinetics and dose
proportionality.
METHODS
This was a double-blind, placebo-controlled, randomized study. There were three
dosing periods. Each subject (n = 12) was randomized to receive one dose of
placebo and two ascending doses of PP 1420, given as a subcutaneous
injection. Blood samples were taken over 24 h to assess pharmacokinetics.
Standard safety and laboratory data were collected. The primary endpoint was
the tolerability of PP 1420. The secondary endpoint was exposure to PP 1420 as
assessed by Cmax and AUC(0,∞).
RESULTS
PP 1420 was well tolerated by all subjects with no serious adverse effects.
Following single subcutaneous doses of PP 1420 at 2, 4 and 8 mg to male
subjects, Cmax was reached at a median tmax of approximately 1 h post dose
(range 0.32–2.00 h). Thereafter, plasma concentrations of PP 1420 declined with
geometric mean apparent terminal elimination t1/2 ranging from 2.42–2.61 h
(range 1.64–3.95 h) across all dose levels.
CONCLUSIONS
Subcutaneous PP 1420 was well tolerated in healthy human subjects at single
doses between 2–8 mg, with no tolerability issues arising. Where observed,
adverse events were not serious, and there was no evidence of a
dose-relationship to frequency of adverse events. The results therefore support
the conduct of clinical trials to investigate efficacy, tolerability and
pharmacokinetics during repeated dosing.