PF 06412562 in Subjects With Advanced Stage Parkinson's Disease

A Phase Ib Safety, Tolerability, and Efficacy Study of Two Days of Oral Split Dose (25/20 mg) Administration of PF 06412562 in Subjects With Advanced Stage Parkinson's Disease

The purpose of this study is to test the safety and tolerability of the investigational drug PF-06412562 compared to the current medical standard of care medication for Parkinson's disease, carbidopa/levodopa. This research also is being done to find out if the investigational drug PF-06412562 can help improve the motor (movement) function, alertness, and cognitive (thinking) skills of people who are considered to be in the advanced-stage of Parkinson's disease. In this study, PF06412562 is 'investigational,' which means that it is experimental and has not been approved by the US Food and Drug Administration (FDA), but can be used in clinical research studies such as this one.

The investigators are conducting a randomized, double-blind, carbidopa/levodopa-controlled crossover safety, tolerability, and efficacy study of the investigational compound, PF-06412562, in advanced Parkinson's patients. The primary purpose of this study is to test the safety and tolerability of the investigational drug PF-06412562 compared to the current medical standard of care medication for Parkinson's disease, carbidopa/levodopa, in these patients. This secondary purpose of this research is to find out if the investigational drug PF-06412562 can help improve the motor (movement) function, alertness, and cognitive (thinking) skills of people who are considered to be in the advanced-stage of Parkinson's disease. This study will inform the field as to whether PF-06412562 is safe and well-tolerated in advanced Parkinson's patients, and also may provide preliminary data on its efficacy in several domains.

Inclusion Criteria:

• Diagnosis of classic PD with history of clinically meaningful response to levodopa
• Disease duration >15 years since diagnosis
• Hoehn & Yahr stage >IV "on" or "off" levodopa
• Consent signed by subject, if possible
• If subject is cognitively impaired, consent signed by power of attorney or legally authorized subject representative
• Assent from the study subject, if possible
• Stable dose of all medications for 60 days prior to Day 1 of first week of study

Exclusion Criteria:

• Atypical parkinsonian syndrome (e.g., never responded to levodopa, and/or atypical signs)
• Acute or unstable medical condition such as heart disease, kidney and liver failure
• History of HIV, hepatitis B and C
• Use of moderate to strong CYP 3A4 modulators (see both inhibitors and inducers in Appendix BB)