Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PF-06649751 in Parkinson`s Disease

Parkinson`s Disease Clinical Trial

Official title:

A Phase 1b, 2-period, Open Label, Multicenter, Dose Escalation Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Pf-06649751 In Subjects With Parkinson`s Disease And Motor Fluctuations

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02224664
• Other study ID #: B7601005
• Secondary ID: 2014-003472-22
• Status: Completed
• Phase: Phase 1
• First received: August 15, 2014
• Last updated: May 6, 2016
• Start date: October 2014
• Est. completion date: March 2016

Study information

• Verified date: May 2016
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 80 Years

Eligibility

Inclusion Criteria:

• Clinical diagnosis of idiopathic Parkinson's Disease with at least 2 out of 3 cardinal characteristics (tremor, rigidity, bradykinesia)

• Mini-Mental State Examination (MMSE) = 25

• Hoehn & Yahr Stage I-III inclusive

• Documented history of end of L-Dopa wearing OFF

• Cohort 5 only: History of dyskinesia following L-Dopa dosing and Score of at least 2 on Part IV, item 4.2 (functional impact of dyskinesia) of the MDS-UPDRS

Exclusion Criteria:

• Atypical/secondary parkinsonism

• History of surgical intervention for Parkinson's Disease

• Dementia/cognitive impairment that can interfere with study assessments

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson`s Disease

Intervention

Drug:
• PF-06649751
Oral daily doses titrated up to 5mg QD
• PF-06649751
Oral daily doses titrated up to 15 mg QD
• PF-06649751
Oral daily doses titrated up to 15 mg QD (slow titration with option to down titrate)
• PF-06649751
Oral daily doses titrated up to 25 mg QD

Locations

Country	Name	City	State
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital -- FOR DRUG SHIPMENT ONLY	Boston	Massachusetts
United States	Neurology Consultants of Dallas, PA	Dallas	Texas
United States	Walnut Hill Medical Center	Dallas	Texas
United States	Rocky Mountain Movement Disorders Center	Englewood	Colorado
United States	Quest Research Institute	Farmington Hills	Michigan
United States	Orange Coast Memorial Medical Center	Fountain Valley	California
United States	The Parkinson's and Movement Disorder Institute	Fountain Valley	California
United States	MD Clinical	Hallandale Beach	Florida
United States	Davita Clinical Research Center	Lakewood	Colorado
United States	Collaborative Neuroscience Network, LLC	Long Beach	California
United States	PRA International	Marlton	New Jersey
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Compass Research, LLC	Orlando	Florida
United States	Carolina Phase I Research, LLC	Raleigh	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) at end of treatment (Day24) and follow up (Day 29)	Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to [study drug] was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.	baseline to day 24, day 29	Yes
Primary	Change from Baseline in Assessment of vital signs (pulse, blood pressure) at end of treatment (Day24) and follow up (Day 29)		baseline to day 24, day 29	Yes
Primary	Change from Baseline in Number of Participants With Laboratory Test Values of Potential Clinical Importance at end of treatment (Day24) and follow up (Day 29)	Pre-defined criteria were established for each laboratory test to define the values that would be identified as of potential clinical importance.	baseline to days 2, 6, 8, 12, 14, 18, 21 and 29	Yes
Primary	Change from Baseline in Assessment of electrocardiogram (ECG) parameters at end of treatment (Day24) and follow up (Day 29)	Measurement of standard 12-lead ECG, single or triplicate	baseline to days 1, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 22, 23, 24, 29	Yes
Primary	Change from Baseline in Number of Participants with categorical scores on the Columbia Suicide Severity Rating Scale (C-SSRS) at end of treatment (Day24) and follow up (Day 29)	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").	baseline to day 6, 12, 18, 24, 29	Yes
Primary	Parkinson's Disease Diary	Parkinson's disease diary based for subjects with motor fluctuations: Total OFF time (hours and percentage); Total ON time (hours and percentage); ON time without dyskinesia (hours and percentage); ON time with dyskinesia (hours and percentage); ON time without troublesome dyskinesia (hours and percentage); ON time with troublesome dyskinesia (hours and percentage); Good ON time (ON time without dyskinesia and ON time without troublesome dyskinesia) (hours and percentage); Total Awake time (hours and percentage); Total Asleep time (hours and percentage).	baseline to day 24	No
Secondary	Maximum Observed Plasma Concentration (Cmax)		Day 3, Day 4, Day 7, Day 8, Day 11, Day 13, Day 14, Day 17, Day 20, Day 22, Day 23, Day 24.	No
Secondary	Area Under the Curve from Time Zero to end of dosing interval (AUCtau)		Day 3, Day 4, Day 7, Day 8, Day 11, Day 13, Day 14, Day 17, Day 20, Day 22, Day 23, Day 24.	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax)		Day 3, Day 4, Day 7, Day 8, Day 11, Day 13, Day 14, Day 17, Day 20, Day 22, Day 23, Day 24.	No
Secondary	Plasma Decay Half-Life (t1/2)		Day 3, Day 4, Day 7, Day 8, Day 11, Day 13, Day 14, Day 17, Day 20, Day 22, Day 23, Day 24.	No
Secondary	Apparent Oral Clearance (CL/F)		Day 3, Day 4, Day 7, Day 8, Day 11, Day 13, Day 14, Day 17, Day 20, Day 22, Day 23, Day 24.	No
Secondary	Trough Concentration (Ctrough)		Day 3, Day 4, Day 7, Day 8, Day 11, Day 13, Day 14, Day 17, Day 20, Day 22, Day 23, Day 24.	No
Secondary	Area under the plasma concentration versus time curve from zero to infinity (AUCinf)		Day 7, Day 13, Day 22	No
Secondary	Area under the plasma concentration versus time curve from zero to the last quantifiable concentration (AUClast)		Day 7, Day 13, Day 22	No
Secondary	Apparent Volume of Distribution (Vz/F)		Day 7, Day 13, Day 22	No
Secondary	Ratio of accumulation for AUCtau (Rac AUCtau)		Day 3, Day 4, Day 7, Day 8, Day 11, Day 13, Day 14, Day 17, Day 20, Day 22, Day 23, Day 24.	No

External Links

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