APPA trial is a placebo controlled trial aiming to determine the safety and tolerability of ascending single and multiple
oral doses of APPA-1 along with the single and multiple oral dose pharmacokinetics (what the body does to a drug) of
APPA-1 constituents (paeonol/apocynin) in healthy subjects and osteoarthritis patients.
The trial will be conducted at the Clinical Research Unit (CRU) at the Royal Liverpool and Broadgreen University
Hospital Trust and will be split into two parts.
Part A will involve 20 healthy subjects studied in 5 groups (group A1 to A5) of 4 subjects receiving a single dose.
Groups A1 to A4 will be male subjects only, Group A5 will consist of female subjects only to assess potential gender
effects. In each group, 3 subjects will receive APPA-1 and 1 will receive placebo, by way of randomisation. All doses
will be administered in a fasted state on day 1. Subjects in group A3 will receive a second dose at least 7 days after
first dose, which will be administered 30 minutes after a high fat breakfast to assess potential food effect. Subjects
will be reviewed 7-10 days post their last dose.
There will be a minimum of 10 days between dose escalations.
Part B will involve 12 patients with osteoarthritis studied in 3 groups (groups B1 to B3) of 4 subjects receiving multiple
doses. Osteoarthritis patients will be assessed to determine the potential for pain relief. In each group, 3 patients will
received APPA-1 and 1 will receive placebo. The dose levels and dietary state for dosing in part B will be subject to
review of safety and pharmacokinetic data from Part A. For all patients, up to two times daily dosing will occur on Days
1 to 13 inclusive and a final single dose will be administered on day 14.