Efficacy, Safety And Tolerability Study In Subjects With Parkinson's Disease

Study Overview
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Brief Summary
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The B7441003 study will assess PF-06412562 for motor benefit in Parkinson's disease subjects. Safety, tolerability and PK of PF-06412562 in Parkinson's disease subjects will also be evaluated.

Official Title
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A Phase 1b, Randomized, Subject And Investigator-Blinded, Sponsor-Open, Placebo Controlled, Cross-Over Efficacy, Safety And Tolerability Study Of Single Oral Split Dose Administration Of PF-06412562 In Subjects With Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: PF-06412562
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects with a diagnosis of idiopathic Parkinson's disease. Daily L-dopa dose between 300 and 1200 mg. MBRS score >1. Exclusion Criteria: Surgical intervention for Parkinson's disease. History of troublesome dyskinesias. Any significant AXIS I psychiatric disease.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: PF-06412562<br>* single oral split dose 30+20 mg QD<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* tablet, matching placebo, QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Finger tapping speed | maximum percent improvement from baseline in finger tapping speed as measured by the Kinesia Technology | 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) |  | 0, 0.5, 1, 2, 4, 5,8,12, 24 hours | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | 0, 0.5, 1, 2, 4, 0, 0.5, 1, 2, 4, 8, 12, 24 hours | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | 0, 0.5, 1, 2, 4, 0, 0.5, 1, 2, 4, 8, 12, 24 hours | 
| Apparent Oral Clearance (CL/F) |  | 0, 0.5, 1, 2, 4, 0, 0.5, 1, 2, 4, 8, 12, 24 hours | 
| Apparent Volume of Distribution (Vz/F) | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. | 0, 0.5, 1, 2, 4, 8, 12, 24 hours | 
| Plasma Decay Half-Life (t1/2) | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | 0, 0.5, 1, 2, 4, 8, 12, 24 hours | 
| Mean Residence Time (MRT) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 0, 0.5, 1, 2, 4, 8, 12, 24 hours | 
| Number of Participants with categorical scores on the Columbia Suicide Severity Rating Scale (C-SSRS) | C-SSRS assessed whether participant experienced following: completed suicide (1), suicide attempt (2) (response of Yes on actual attempt), preparatory acts toward imminent suicidal behavior (3)(Yes on preparatory acts or behavior), suicidal ideation (4) (Yes on wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7)(Yes on Has subject engaged in non-suicidal self-injurious behavior). | 24 hours |