Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PF-06649751 in Parkinson`s Disease

This study will be an open label, dose escalation study to investigate the safety,
tolerability, pharmacokinetics and pharmacodynamics of repeated daily quaque die (QD) doses
given over 21 days (Day 3 to Day 23) to sequential cohorts of subjects with Parkinson's
disease. Each cohort will have 2 study periods. For each cohort, subjects will enter Period
1 and if they meet criteria, approximately 12 subjects will be enrolled into Period 2 and
dosed with PF 06649751. Based on results observed in a previous study, Cohorts 1 and 2 will
not be conducted. Cohorts 3 - 6 will test doses uptitrated to 5 mg, 15 mg and 25 mg QD.
Doses may be modified based on emerging safety, tolerability and PK data, but the maximum
daily dose that will be given in any cohort will have PK predictions at steady state that
are anticipated to be below toxicokinetic limits. An option for down titration to the
previous dose level is available should the investigator consider that an AE is intolerable.
Following down titration, a single up titration to the next dose level may be attempted if
the subject remains symptom free for at least 48 hrs. Safety, tolerability and PK data of
Cohort 3 will be reviewed prior to initiating the dosing in Cohorts 4 and 5. Available
safety, tolerability and PK data up to Day 24 of at least 5 subjects from Cohorts 4 will be
reviewed prior to initiating the dosing in Cohort 6.