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

Pfizer

Status and phase: Completed; Phase 1

Conditions: Parkinson's Disease

Treatments: Drug: PF-06649751

Study type: Interventional

Funder types: Industry

Identifiers

NCT02224664

2014-003472-22 (EudraCT Number)

B7601005

Details and patient eligibility

About

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.

Enrollment: 50 patients

Sex: All

Ages: 30 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

50 participants in 4 patient groups

Cohort 3

Experimental group

Description:

Titration of PF-06649751 up to 5 mg QD

Treatment:

Drug: PF-06649751

Drug: PF-06649751

Drug: PF-06649751

Drug: PF-06649751

Cohort 4

Experimental group

Description:

Titration of PF-06649751 up to 15 mg QD

Treatment:

Drug: PF-06649751

Drug: PF-06649751

Drug: PF-06649751

Drug: PF-06649751

Cohort 5

Experimental group

Description:

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

Treatment:

Drug: PF-06649751

Drug: PF-06649751

Drug: PF-06649751

Drug: PF-06649751

Cohort 6

Experimental group

Description:

Titration of PF-0649751 up to 25 mg QD

Treatment:

Drug: PF-06649751

Drug: PF-06649751

Drug: PF-06649751

Drug: PF-06649751