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PF 06412562 in Subjects With Advanced Stage Parkinson's Disease

Phase 1
Completed
Conditions
Parkinson Disease
Interventions
Drug: Standard of Care Placebo
Registration Number
NCT03665454
Lead Sponsor
Milton S. Hershey Medical Center
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
8
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
PF-06412562PF-06412562Subjects will receive 25 mg of PF-06412562 twice daily on study Days 2 and 3, along with placebo carbidopa/levodopa dosed at these times. Additional carbidopa/levodopa placebo capsules also will be administered according to the subject's home regimen.
Standard of Care carbidopa/levodopaStandard of Care PlaceboSubjects will take placebo tablets for the PF-06412562 twice daily on study Days 2 and 3, along with active carbidopa/levodopa (25/100 mg) administered at these times. Additional active carbidopa/levodopa capsules also will be administered according to the subject's home regimen.
Primary Outcome Measures
NameTimeMethod
Safety and tolerability of PF-06412562 assessed by blood sample resultsDay 4

Red blood cell count (M/uL)

Safety and tolerability of PF-06412562 assessed by cardiology testing/cardiac autonomic functionX3 on Days 3 over 15 min each time

heart rate (beats/min), sinus arrhythmia (beats/min)

Safety and tolerability of PF-06412562 assessed by Columbia Suicide RatingX1 on Day 4

C-SSRS measures suicidal ideation and/or behavior. Rated from Category 1-10 with Category 1 being the least severe, and Category 10 representing the most severe, i.e. completing suicide.

Safety and tolerability of PF-06412562 assessed by vital signsX2 on Day 4

temperature (F)

Safety and tolerability of PF-06412562 assessed by UPDRS-IVX3 on Days 3

UPDRS-IV (United Parkinson's Disease Rating Scale): each questions scored on scale of 0 to 4, where 0= not present, 4= severe; subscales are summed to yield a total score, min total score:0, max total score:81; higher score corresponds to increased disease severity

Secondary Outcome Measures
NameTimeMethod
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 PDGlobal Impression of Change: X3 on Days 2 and 3; Caregiver Perception of Change: X1 on Day 3

• Clinician Global Impression of Change score: measures change in disease symptoms per clinician's judgement. Each item rated 1-7, 1=marked improvement, 7= marked worsening; min Caregiver perception of change interview: interviews with participants' caregiver(s). Open-ended questions elicit open-ended answers about subject's behavior, appearance, cognition, etc. over the study

Trial Locations

Locations (1)

Penn State Milton S. Hershey Medical Center

🇺🇸

Hershey, Pennsylvania, United States

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