Conditions: Parkinson's Disease
Allocation: NON_RANDOMIZED | Intervention model: 
Enrollment: 50
Healthy volunteers: no

Brief summary:
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.

Detailed description:

Arms:
arm 1: Titration of PF-06649751 up to 5 mg QD arm 2: Titration of PF-06649751 up to 15 mg QD arm 3: Titration of PF-06649751 up to 15 mg QDi n subjects with Levodopa-induced dyskinesias (LID) arm 4: Titration of PF-0649751 up to 25 mg QD

Interventions: intervention 1: PF-06649751 intervention 2: PF-06649751 intervention 3: PF-06649751 intervention 4: PF-06649751
Intervention descriptions: intervention 1: Oral daily doses titrated up to 5mg QD intervention 2: Oral daily doses titrated up to 15 mg QD intervention 3: Oral daily doses titrated up to 15 mg QD (slow titration with option to down titrate) intervention 4: Oral daily doses titrated up to 25 mg QD

Protocol document: