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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02224664
• Date of registration: 15/08/2014
• Prospective Registration: Yes
• Primary sponsor: Pfizer
• Public title: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PF-06649751 in Parkinson`s Disease
• Scientific 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
• Date of first enrolment: October 2014
• Target sample size: 50
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02224664
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Primary purpose: Basic Science. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Belgium, United States

Contacts

• Name: Pfizer CT.gov Call Center
• Affiliation: Pfizer

Key inclusion & exclusion 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



Age minimum: 30 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Parkinson`s Disease

Intervention(s)

Drug: PF-06649751

Primary Outcome(s)

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time Frame: Baseline (Day 1) up to Day 30]

Number of Participants With Clinically Significant Change From Baseline in Physical Examination Findings [Time Frame: Baseline up to Day 30]

Number of Participants With Clinically Significant Neurological Examination Abnormality [Time Frame: Baseline up to Day 30]

Change From Baseline in Parkinson's Disease Diary For Participants With Motor Fluctuations at Day 13 [Time Frame: Baseline, Day 13]

Number of Participants With Electrocardiogram (ECG) Abnormalities [Time Frame: Baseline up to Day 30]

Number of Participants With Laboratory Test Abnormalities [Time Frame: Baseline up to Day 30]

Change From Baseline in Parkinson's Disease Diary For Participants With Motor Fluctuations at Day 20 [Time Frame: Baseline, Day 20]

Number of Participants With Vital Sign Abnormalities [Time Frame: Baseline up to Day 30]

Number of Participants With Categorical Scores on The Columbia Suicide Severity Rating Scale (C-SSRS) [Time Frame: Baseline up to Day 30]

Secondary Outcome(s)

Time to Reach Maximum Observed Plasma Concentration (Tmax) of L-Dopa [Time Frame: Pre-dose, 0.5, 1, 2, 4 and 8 hours post-dose on Day 1]

Apparent Clearance (CL/F) of PF-06649751 [Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8 and 12 hour post-dose on Day 22]

Area Under the Curve From Time Zero Extrapolated to Infinite Time of L-Dopa [Time Frame: Pre-dose, 0.5, 1, 2, 4 and 8 hours post-dose on Day 1]

Area Under the Curve From Time Zero to End of Dosing Interval of PF-06649751 [Time Frame: Pre-dose on Day 3, 4, 8, 11, 14, 17, 20, Pre-dose, 0.5, 1, 1.5, 2, 4, 8 and 12 hour post-dose on Day 7, 13, 22]

Maximum Observed Plasma Concentration (Cmax) of PF-06649751 [Time Frame: Pre-dose on Day 3, 4, 8, 11, 14, 17, 20, Pre-dose, 0.5, 1, 1.5, 2, 4, 8 and 12 hour post-dose on Day 7, 13, 22]

Maximum Observed Plasma Concentration (Cmax) of L-Dopa [Time Frame: Pre-dose, 0.5, 1, 2, 4 and 8 hours post-dose on Day 1]

Apparent Clearance (CL/F) of L-Dopa [Time Frame: Pre-dose, 0.5, 1, 2, 4 and 8 hours post-dose on Day 1]

Apparent Volume of Distribution (Vz/F) of L-Dopa [Time Frame: Pre-dose, 0.5, 1, 2, 4 and 8 hours post-dose on Day 1]

Area Under the Curve From Time Zero to Last Quantifiable Concentration of L-Dopa [Time Frame: Pre-dose, 0.5, 1, 2, 4 and 8 hours post-dose on Day 1]

Minimum Observed Plasma Trough Concentration (Cmin) of PF-06649751 [Time Frame: Pre-dose on Day 3, 4, 8, 11, 14, 17, 20, Pre-dose, 0.5, 1, 1.5, 2, 4, 8 and 12 hour post-dose on Day 7, 13, 22]

Ratio of Accumulation for Area Under the Curve From Time Zero to End of Dosing Interval of PF-06649751 [Time Frame: Pre-dose on Day 3, 4, 8, 11, 14, 17, 20, Pre-dose, 0.5, 1, 1.5, 2, 4, 8 and 12 hour post-dose on Day 7, 13, 22]

Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06649751 [Time Frame: Pre-dose on Day 3, 4, 8, 11, 14, 17, 20, Pre-dose, 0.5, 1, 1.5, 2, 4, 8 and 12 hour post-dose on Day 7, 13, 22]

Terminal Half-Life (t1/2) of L-Dopa [Time Frame: Pre-dose, 0.5, 1, 2, 4 and 8 hours post-dose on Day 1]

Secondary ID(s)

B7601005

2014-003472-22

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 27/03/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02224664