PF-06669571 In Subjects With Idiopathic Parkinson's Disease

Study Overview
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Brief Summary
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This study is designed to assess safety, tolerability and pharmacokinetic data for multiple doses of PF-06669571 in subjects with idiopathic Parkinson's disease. In addition, this study will assess whether PF-06669571 is able to demonstrate superior efficacy compared with placebo in the treatment of the motor symptoms of idiopathic Parkinson's disease.

Official Title
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A Phase 1b, Double Blind, Sponsor Open, Randomized, Parallel, Group Multiple Dose Study Examining The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Pf-06669571 In Subjects With Idiopathic Parkinson's Disease.

Conditions
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Idiopathic Parkinson's Disease

Intervention / Treatment
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* Drug: PF-06669571
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have a clinical diagnosis of idiopathic Parkinson's disease and presence of at least 2 out of 3 cardinal characteristics (tremor, rigidity and/or bradykinesia). Must be Hoehn & Yahr Stage II-III inclusive and experiencing motor fluctuations in the form of end-of-dose wearing off during the morning hours or early morning akinesia. Subjects should be able to recognize their wearing off symptoms and verify that they usually improve after their next dose of Parkinson's disease medication. Subjects should be able to recognize drug-induced dyskinesias and verify whether or not they are troublesome. Exclusion Criteria: - History or clinical features consistent with an atypical parkinsonian syndrome, (for example: ataxia, dystonia, clinically significant orthostatic hypotension.

Ages Eligible for Study
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Minimum Age: 45 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: PF-06669571<br>Once daily (QD) for 7 days | Drug: PF-06669571<br>* 1 milligram (mg) QD for 3 days followed by 3 mg QD for 4 days<br>|
| Placebo Comparator: Placebo<br>QD for 7 days | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Percent Change From Baseline in Movement Disorder Society-Sponsor Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III at Day 7. | The total MDS-UPDRS score is the most common method of evaluating the severity of Parkinson's disease across behaviors, activities of daily living, motor abilities, and other complications of Parkinson's disease. The MDS-UPDRS focuses primarily on measuring impairments associated with Parkinson's disease, with subsections organized according to motor and non-motor aspects of the disease. Part III assesses the motor signs of Parkinson's disease. Higher total scores indicate more severe motor signs of Parkinson's disease. Negative changes from baseline indicate improvement. MDS-UPDRS Part III total motor score is comprised of 33 sub-scores based on 18 items, several with right, left or other body distribution scores. Each question is anchored with five responses that are linked to commonly accepted clinical terms: 0 = normal, 1 = slight, 2 = mild, 3 = moderate and 4 = severe. | Day 7 | 
| Number of Participants in Each Columbia Classification Algorithm of Suicide Assessment (C-CASA) Category by Study Visit on Day -2, Day 8 or Early Withdrawal, and Early Withdrawal/Follow-Up Visit | The number of participants in each C-CASA category was mapped from Columbia-Suicide Severity Rating Scale (C-SSRS) data. 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 or some intent to act, 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). | Day -2, Day 8, and follow-up visit (Day 7 - 14 after last dose of PF-06669571) | 
| Number of Participants With New Onset and Worsening of Post-Baseline Suicidality. | Number of participants with new onset and worsening of post-baseline suicidality was reported | Day 8 or follow-up visit (Day 7 - 14 after last dose of PF-06669571) | 
| Number of Participants With Treatment Emergent Adverse Events (All Causalities) | An adverse event (AE) was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. | Day 1 to 28 calendar days after the last dose of investigational product | 
| Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Absolute Values) | Number of participants with supine and standing vital signs data of absolute values meeting criteria of potential clinical concern. Absolute values were analyzed for supine/standing systolic blood pressure (SBP), supine/standing diastolic blood pressure (DBP), and supine/standing pulse rate. Number of participants with vital signs data meeting the following criteria was reported: (1) absolute supine SBP <90 millimeters of mercury (mmHg); (2) absolute standing SBP <90 mmHg; (3)absolute supine DBP<50mmHg; (4)absolute standing DBP<50mmHg (5) absolute supine pulse rate <40 beats per minute (bpm); (6) absolute supine pulse rate >120 bpm;(7) absolute standing pulse rate <40 bpm; (8) absolute standing pulse rate >140 bpm. | Screening, Days -1, 1, 7 and 8, and follow-up visit | 
| Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Increase From Baseline) | The number of participants with vital signs data of maximum increase from baseline meeting the following criteria was reported: Criterion A: maximum increase from baseline in supine systolic BP (SBP) >=30 millimeters of mercury (mmHg); Criterion B maximum increase from baseline in standing SBP >=30 mmHg; Criterion C: maximum increase from baseline in supine diastolic BP(DBP) >=20 mmHg; Criterion D: maximum increase from baseline in standing diastolic BP(DBP) >=20 mmHg | Screening, Days -1, 1, 7 and 8, and follow-up visit | 
| Number of Participants With Supine and Standing Vital Sign Abnormalities (Decrease From Baseline) | The number of participants with vital signs data of maximum decrease from baseline meeting the following criteria was reported: Criterion A: maximum decrease from baseline in supine systolic BP (SBP) >=30 mmHg; Criterion B: maximum decrease from baseline in standing SBP >=30 mmHg; Criterion C: maximum decrease from baseline in supine diastolic BP(DBP) >=20 mmHg; Criterion D: maximum decrease from baseline in standing diastolic BP(DBP) >=20 mmHg | Screening, Days -1, 1, 7 and 8, and follow-up visit | 
| Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern (Absolute Value) | The number of participants with ECG absolute values meeting the following criteria was reported: Criterion A: maximum PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization) >=300 msec; Criterion B: maximum QRs complex(time from Q wave to the end of S wave, corresponding to ventricle depolarization) >=140 msec; Criterion C: maximum QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole, corrected for heart rate using Fridericia's formula) 450-<480 msec; Criterion D: maximum QTcF interval 480-<500 msec; Criterion E: maximum QTcF interval (Fridericia's correction) >=500 msec | Screening, Days 1, 7, and 8, and follow-up visit | 
| Primary: Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern(Increase From Baseline) | Number of participants with ECG(standard 12-lead) meeting the following criteria was reported: Criterion A: maximum PR interval increase from baseline percentage change (PctChg)>=25/50%; Criterion B: maximum QRs complex increase from baseline PctChg >=50%; Criterion C: maximum QTcF interval increase from baseline 30<=change<60 msec; Criterion D: maximum QTcF interval increase from baseline change >=60 msec. | Screening, Days 1, 7, and 8, and follow-up visit | 
| Number of Participants With Laboratory Abnormalities That Met Categorical Criteria for Concern (Without Regard to Baseline Abnormality) | Number of participants with a laboratory abnormality meeting specified criteria. The laboratory test included: hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, absolute total neutrophils, absolute eosinophils, absolute basophils, absolute monocytes, and absolute lymphocytes),liver function(total bilirubin, direct bilirubin, aspartate, aspartate aminotransferase, alanine, alanine aminotransferase, alkaline phosphatase, total protein, and albumin), renal function (blood urea nitrogen, creatinine, and uric acid), electrolytes (sodium, potassium, chloride, calcium, and venous bicarbonate), clinical chemistry(glucose) ,and urinalysis (pH, qualitative glucose, qualitative protein, qualitative blood, qualitative ketones, qualitative bilirubin, nitrites, leukocyte esterase, urine urobilinogen, urine leukocyte, esterase and microscopy). | Screening, Days 1, 4, and 7, and follow-up visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of PF-06669571 on Day 1 and Day 7 | Cmax of PF-06669671 was observed directly from data on Day 1 and Day 7 | 0, 1, 3, 5, 8 and 12 hours post-dose on both Day 1 and Day 7 | 
| Area Under Curve From Time Zero to 12 Hours (AUC12) of PF-06669571 on Day 1 and Day 7 | AUC12 of PF-06669571 refers to the area under the curve from time zero to 12 hours post dose on Day 1 and Day 7. AUC12 was determined by using linear/log trapezoidal method. | 0, 1, 3, 5, 8 and 12 hours post-dose on both Day 1 and Day 7 | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06669571 on Day 1 and Day 7 | Tmax of PF-06669571 was observed directly from data on Day 1 and Day 7, as time of first occurrence. | 0, 1, 3, 5, 8 and 12 hours post-dose on both Day 1 and Day 7 | 
| Area Under Curve From Time Zero to 24 Hours (AUC24) of PF-06669571 on Day 7 | AUC24 of PF-06669571 refers to the area under the curve from time zero to 24 hours post dose on Day 7. AUC24 was determined by using linear/log trapezoidal method | 0, 1, 3, 5, 8, 12 and 24 hours post-dose on Day 7 |