A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of PF-06649751 in Subjects With Idiopathic Parkinson's Disease

Study Overview
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Brief Summary
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This is a study with two sequential cohorts, each with three treatment periods. Single doses of PF-06649751 will be tested in this study, starting at a low dose and escalating to a dose projected to be under the current limits for drug concentration. Each cohort will aim to achieve approximately 9 completers. Primary endpoint is safety and tolerability, secondary endpoint is MDS-UPDRS part III.

Official Title
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A Phase 1, Double Blind, Sponsor Open, Randomized, Placebo-controlled, Single Ascending Dose Study To Investigate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Pf-06649751 In Subjects With Idiopathic Parkinson's Disease

Conditions
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Idiopathic Parkinson Disease

Intervention / Treatment
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* Drug: PF-06649751
* Drug: Trimethobenzamide Hydrochloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: L-DOPA-responsiveness Hoehn & Yahr Stage II-III inclusive Experiencing motor fluctuations Stable daily dose of L-DOPA of at least 300 mg Females on non-childbearing potential and male subjects Exclusion Criteria: History of troublesome dyskinesias History of surgical intervention for Parkinson's disease

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 85 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Three single doses over three periods. For each of the three periods, subjects will be crossed-over from placebo or PF-06649751. Each PF-06649751 dose is separated by at least one week. | Drug: PF-06649751<br>* Subjects completing all three treatment periods will be administered two doses. Doses: 0.75mg, 1.5mg, 3mg, 6mg, 9mg. Tablets in the form of 0.25mg or 1 mg.<br>Drug: Trimethobenzamide Hydrochloride<br>* 300mg TID, Capsules. Optional in both Cohorts.<br>Drug: Placebo<br>* Subjects completing all three treatment periods will be receiving placebo once.<br>|
| Experimental: Cohort 2<br>Three single doses over three periods. For each of the three periods, subjects will be crossed-over from placebo or PF-06649751. Each PF-06649751 dose is separated by at least one week. | Drug: PF-06649751<br>* Subjects completing all three treatment periods will be administered two doses. Doses: 0.75mg, 1.5mg, 3mg, 6mg, 9mg. Tablets in the form of 0.25mg or 1 mg.<br>Drug: Trimethobenzamide Hydrochloride<br>* 300mg TID, Capsules. Optional in both Cohorts.<br>Drug: Placebo<br>* Subjects completing all three treatment periods will be receiving placebo once.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and proportion of subjects with Adverse Events (AEs) |  | Day 1 through 61 | 
| Number of participants with vital signs data that meet criteria of potential clinical concern |  | Day 1 through 61 | 
| Number of participants with ECG data that meet criteria of potential clinical concern |  | Day 1 through 61 | 
| Number of participants with abnormal clinically significant laboratory measurements |  | Day 1 through 61 | 
| C-SSRS (suicidality assessment) |  | Day 1 through 61 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MDS-UPDRS part III | MDS - Unified Parkinson's Disease Rating Scale Part III | Day 1, Periods 1-3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pakinson's Disease, Movement Disorders