Clinical trial NCT03665454: PF 06412562 in Subjects With Advanced Stage Parkinson's Disease
Official title: A Phase Ib Safety, Tolerability, and Efficacy Study of Two Days of Oral Split Dose (25/20 mg) Administration of PF 06412562 in Subjects With Advanced Stage Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson Disease
Keywords: Parkinson's Disease
Parkinson Disease
End-Stage
Progressed
Advanced Parkinson's Disease
End-Stage Parkinson's Disease
Clinical intervention
Double-blind, randomized
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2018-09-11
Enrollment: 8
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Subjects will participate in study for 2 consecutive weeks. Days 2-3 of Week 1, they will be blindly and randomly assigned to one of two treatment arms (study drug PF-06412562 or standard of care carbidopa/levodopa). Whichever treatment arm they did not receive during Week 1, they will receive during Days 2-3 of Week 2.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test the safety and tolerability of the investigational drug PF-06412562 compared to the current medical standard of care medication for Parkinson's disease, carbidopa/levodopa. This research also is being done to find out if the investigational drug PF-06412562 can help improve the motor (movement) function, alertness, and cognitive (thinking) skills of people who are considered to be in the advanced-stage of Parkinson's disease. In this study, PF06412562 is 'investigational,' which means that it is experimental and has not been approved by the US Food and Drug Administration (FDA), but can be used in clinical research studies such as this one.

Detailed description: The investigators are conducting a randomized, double-blind, carbidopa/levodopa-controlled crossover safety, tolerability, and efficacy study of the investigational compound, PF-06412562, in advanced Parkinson's patients. The primary purpose of this study is to test the safety and tolerability of the investigational drug PF-06412562 compared to the current medical standard of care medication for Parkinson's disease, carbidopa/levodopa, in these patients. This secondary purpose of this research is to find out if the investigational drug PF-06412562 can help improve the motor (movement) function, alertness, and cognitive (thinking) skills of people who are considered to be in the advanced-stage of Parkinson's disease. This study will inform the field as to whether PF-06412562 is safe and well-tolerated in advanced Parkinson's patients, and also may provide preliminary data on its efficacy in several domains.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of classic PD with history of clinically meaningful response to levodopa
* Disease duration \>15 years since diagnosis
* Hoehn \& Yahr stage \>IV "on" or "off" levodopa
* Consent signed by subject, if possible
* If subject is cognitively impaired, consent signed by power of attorney or legally authorized subject representative
* Assent from the study subject, if possible
* Stable dose of all medications for 60 days prior to Day 1 of first week of study

Exclusion Criteria:

* Atypical parkinsonian syndrome (e.g., never responded to levodopa, and/or atypical signs)
* Acute or unstable medical condition such as heart disease, kidney and liver failure
* History of HIV, hepatitis B and C
* Use of moderate to strong CYP 3A4 modulators (see both inhibitors and inducers in Appendix BB)

Primary outcomes:
measure: Safety and tolerability of PF-06412562 assessed by blood sample results
timeFrame: Day 1
measure: Safety and tolerability of PF-06412562 assessed by blood sample results
timeFrame: Day 1
measure: Safety and tolerability of PF-06412562 assessed by blood sample results
timeFrame: Day 1
measure: Safety and tolerability of PF-06412562 assessed by blood sample results
timeFrame: Day 1
measure: Safety and tolerability of PF-06412562 assessed by blood sample results
timeFrame: Day 1
measure: Safety and tolerability of PF-06412562 assessed by blood sample results
timeFrame: Day 1
measure: Safety and tolerability of PF-06412562 assessed by blood sample results
timeFrame: Day 4
measure: Safety and tolerability of PF-06412562 assessed by blood sample results
timeFrame: Day 4
measure: Safety and tolerability of PF-06412562 assessed by blood sample results
timeFrame: Day 4
measure: Safety and tolerability of PF-06412562 assessed by blood sample results
timeFrame: Day 4
measure: Safety and tolerability of PF-06412562 assessed by blood sample results
timeFrame: Day 4
measure: Safety and tolerability of PF-06412562 assessed by blood sample results
timeFrame: Day 4
measure: Safety and tolerability of PF-06412562 assessed by blood sample results
timeFrame: Day 4
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: Time Frame: Vital signs: X2 on Day 1
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X2 on Day 1
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X2 on Day 1
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X2 on Day 1
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X2 on Day 1
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X2 on Day 1
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X3 on Days 2
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X3 on Days 2
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X3 on Days 2
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X3 on Days 2
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X3 on Days 2
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X3 on Days 3
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X3 on Days 3
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X3 on Days 3
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X3 on Days 3
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X3 on Days 3
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X3 on Days 3
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X2 on Day 4
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X2 on Day 4
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X2 on Day 4
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X2 on Day 4
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X2 on Day 4
measure: Safety and tolerability of PF-06412562 assessed by vital signs
timeFrame: X2 on Day 4
measure: Safety and tolerability of PF-06412562 assessed by cardiology testing/cardiac autonomic function
timeFrame: X1 on Day 1 over 15 min
measure: Safety and tolerability of PF-06412562 assessed by cardiology testing/cardiac autonomic function
timeFrame: X1 on Day 1 over 15 min
measure: Safety and tolerability of PF-06412562 assessed by cardiology testing/cardiac autonomic function
timeFrame: X3 on Days 2 over 15 min each time
measure: Safety and tolerability of PF-06412562 assessed by cardiology testing/cardiac autonomic function
timeFrame: X3 on Days 2 over 15 min each time
measure: Safety and tolerability of PF-06412562 assessed by cardiology testing/cardiac autonomic function
timeFrame: X3 on Days 3 over 15 min each time
measure: Safety and tolerability of PF-06412562 assessed by cardiology testing/cardiac autonomic function
timeFrame: X3 on Days 3 over 15 min each time
measure: Safety and tolerability of PF-06412562 assessed by UPDRS-IV
timeFrame: X3 on Days 2
measure: Safety and tolerability of PF-06412562 assessed by UPDRS-IV
timeFrame: X3 on Days 3
measure: Safety and tolerability of PF-06412562 assessed by Columbia Suicide Rating
timeFrame: X1 on Day 1
measure: Safety and tolerability of PF-06412562 assessed by Columbia Suicide Rating
timeFrame: X1 on Day 4
Secondary outcomes:
measure: Pilot data on potential efficacy of PF-06412562 compared to the standard of care treatment (i.e., carbidopa/levodopa) on overall signs and quality of life in subjects with advanced PD
timeFrame: Global Impression of Change: X3 on Days 2 and 3; Caregiver Perception of Change: X1 on Day 3
Other outcomes:
measure: Pilot data on potential efficacy of PF 06412562 on individual domains of alertness
timeFrame: Once before and X2 after drug administration on Days 2 & 3
measure: Pilot data on potential efficacy of PF 06412562 on individual domains of cogitation
timeFrame: Once before and X2 after drug administration on Days 2 & 3
measure: Pilot data on potential efficacy of PF 06412562 on individual domains of motor
timeFrame: Once before and X2 after drug administration on Days 2 & 3
measure: Pilot data on potential efficacy of PF 06412562 on individual domains of sleep
timeFrame: PSG sleep study: Days 1-3 at bedtime
Locations:
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
Study officials:
affiliation: Milton S. Hershey Medical Center
name: Xuemei Huang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fernandez-Mendoza J, Puzino K, Amatrudo G, Bourchtein E, Calhoun SL, Plante DT, Kaplan K. The Hypersomnia Severity Index: reliability, construct, and criterion validity in a clinical sample of patients with sleep disorders. J Clin Sleep Med. 2021 Nov 1;17(11):2249-2256. doi: 10.5664/jcsm.9426.
citation: Huang X, Lewis MM, Van Scoy LJ, De Jesus S, Eslinger PJ, Arnold AC, Miller AJ, Fernandez-Mendoza J, Snyder B, Harrington W, Kong L, Wang X, Sun D, Delnomdedieu M, Duvvuri S, Mahoney SE, Gray DL, Mailman RB. The D1/D5 Dopamine Partial Agonist PF-06412562 in Advanced-Stage Parkinson's Disease: A Feasibility Study. J Parkinsons Dis. 2020;10(4):1515-1527. doi: 10.3233/JPD-202188.