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

NCT ID: NCT02224664

Last Updated: 2017-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2016-03-31

Brief 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.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Cohort 3

Titration of PF-06649751 up to 5 mg QD

Group Type: EXPERIMENTAL

PF-06649751

Intervention Type: DRUG

Oral daily doses titrated up to 5mg QD

Cohort 4

Titration of PF-06649751 up to 15 mg QD

Group Type: EXPERIMENTAL

PF-06649751

Intervention Type: DRUG

Oral daily doses titrated up to 15 mg QD

Cohort 5

Titration of PF-06649751 up to 15 mg QDi n subjects with Levodopa-induced dyskinesias (LID)

Group Type: EXPERIMENTAL

PF-06649751

Intervention Type: DRUG

Oral daily doses titrated up to 15 mg QD (slow titration with option to down titrate)

Cohort 6

Titration of PF-0649751 up to 25 mg QD

Group Type: EXPERIMENTAL

PF-06649751

Intervention Type: DRUG

Oral daily doses titrated up to 25 mg QD

Interventions

PF-06649751

Oral daily doses titrated up to 5mg QD

Intervention Type: DRUG

PF-06649751

Oral daily doses titrated up to 15 mg QD

Intervention Type: DRUG

PF-06649751

Oral daily doses titrated up to 15 mg QD (slow titration with option to down titrate)

Intervention Type: DRUG

PF-06649751

Oral daily doses titrated up to 25 mg QD

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

Orange Coast Memorial Medical Center

Fountain Valley, California, United States

The Parkinson's and Movement Disorder Institute

Fountain Valley, California, United States

Collaborative Neuroscience Network, LLC

Long Beach, California, United States

Rocky Mountain Movement Disorders Center

Englewood, Colorado, United States

Davita Clinical Research Center

Lakewood, Colorado, United States

MD Clinical

Hallandale, Florida, United States

Compass Research, LLC

Orlando, Florida, United States

Atlanta Center for Medical Research

Atlanta, Georgia, United States

Massachusetts General Hospital -- FOR DRUG SHIPMENT ONLY

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Quest Research Institute

Farmington Hills, Michigan, United States

PRA International

Marlton, New Jersey, United States

Carolina Phase I Research, LLC

Raleigh, North Carolina, United States

Lynn Health Science Institute

Oklahoma City, Oklahoma, United States

Neurology Consultants of Dallas, PA

Dallas, Texas, United States

Walnut Hill Medical Center

Dallas, Texas, United States

Pfizer Clinical Research Unit

Brussels, , Belgium

Countries

United States; Belgium

References

Sohur US, Gray DL, Duvvuri S, Zhang Y, Thayer K, Feng G. Phase 1 Parkinson's Disease Studies Show the Dopamine D1/D5 Agonist PF-06649751 is Safe and Well Tolerated. Neurol Ther. 2018 Dec;7(2):307-319. doi: 10.1007/s40120-018-0114-z. Epub 2018 Oct 25.

Reference Type: DERIVED

PMID: 30361858 (View on PubMed)

Related Links

https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B7601005&StudyName=Safety%2C%20Tolerability%2C%20Pharmacokinetics%20and%20Pharmacodynamics%20of%20PF-06649751%20in%20Parkinson%60s%20Disease%20

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Other Identifiers

2014-003472-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

B7601005

Identifier Type: -

Identifier Source: org_study_id