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Completed

NCT Number: NCT03665454

PF 06412562 in Subjects With Advanced Stage Parkinson's Disease

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.

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Key information

Conditions

Parkinson Disease Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Movement Disorders Nervous System Diseases Neurodegenerative Diseases Parkinsonian Disorders Synucleinopathies

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

PF-06412562

Drug

PF-06412562 is a dopamine agonist developed by Pfizer Inc. into a tablet form for oral usage. It will be provided as 5 mg tablets. Thus, to administer the 25 mg dose, 5 x 5 mg tablets will be given; and to administer the 20 mg dose, 4 x 5 mg tablets will be administered.

Standard of Care Placebo

Drug

25/100 mg tablet(s) of carbidopa/levodopa will be encapsulated and administered according to the subject's home regimen.

Other names: Sinemet

Primary outcomes

  1. Safety and tolerability of PF-06412562 assessed by blood sample results

    Time frame: Day 1

    NA (mmol/L), K(mmol/L), HCO3(mmol/L)

  2. Safety and tolerability of PF-06412562 assessed by blood sample results

    Time frame: Day 1

    Ca (mg/dL), Mg (mg/dL), BUN( mg/dL), Creatinine (mg/dL), Bilirubin (mg/dL)

  3. Safety and tolerability of PF-06412562 assessed by blood sample results

    Time frame: Day 1

    AST (U/L), ALT (U/L)

  4. Safety and tolerability of PF-06412562 assessed by blood sample results

    Time frame: Day 1

    white blood cell count (K/uL), platelets (K/uL)

  5. Safety and tolerability of PF-06412562 assessed by blood sample results

    Time frame: Day 1

    Hematocrit (%)

  6. Safety and tolerability of PF-06412562 assessed by blood sample results

    Time frame: Day 1

    hemoglobin (g/dL)

  7. Safety and tolerability of PF-06412562 assessed by blood sample results

    Time frame: Day 4

    NA (mmol/L), K(mmol/L), HCO3(mmol/L)

  8. Safety and tolerability of PF-06412562 assessed by blood sample results

    Time frame: Day 4

    Ca (mg/dL), Mg (mg/dL), BUN (mg/dL), creatinine (mg/dL), bilirubin (mg/dL)

  9. Safety and tolerability of PF-06412562 assessed by blood sample results

    Time frame: Day 4

    AST (U/L), ALT (U/L)

  10. Safety and tolerability of PF-06412562 assessed by blood sample results

    Time frame: Day 4

    white blood cell count (K/uL), platelets (K/uL)

  11. Safety and tolerability of PF-06412562 assessed by blood sample results

    Time frame: Day 4

    hematocrit (%)

  12. Safety and tolerability of PF-06412562 assessed by blood sample results

    Time frame: Day 4

    hemoglobin (g/dL)

  13. Safety and tolerability of PF-06412562 assessed by blood sample results

    Time frame: Day 4

    Red blood cell count (M/uL)

  14. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: Time Frame: Vital signs: X2 on Day 1

    height (inches)

  15. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X2 on Day 1

    weight (lbs)

  16. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X2 on Day 1

    blood pressure (mmHg)

  17. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X2 on Day 1

    heart rate (bpm)

  18. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X2 on Day 1

    respiratory rate (breathes/min)

  19. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X2 on Day 1

    temperature (F)

  20. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X3 on Days 2

    height (inches)

  21. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X3 on Days 2

    blood pressure (mmHg)

  22. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X3 on Days 2

    heart rate (bpm)

  23. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X3 on Days 2

    respiratory rate (breathes/min)

  24. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X3 on Days 2

    temperature (F)

  25. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X3 on Days 3

    height (inches)

  26. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X3 on Days 3

    weight (lbs)

  27. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X3 on Days 3

    blood pressure (mmHg)

  28. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X3 on Days 3

    heart rate (bpm)

  29. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X3 on Days 3

    respiratory rate (breathes/min)

  30. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X3 on Days 3

    temperature (F)

  31. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X2 on Day 4

    height (inches)

  32. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X2 on Day 4

    weight (lbs)

  33. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X2 on Day 4

    blood pressure (mmHg)

  34. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X2 on Day 4

    heart rate (bpm)

  35. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X2 on Day 4

    respiratory rate (breathes/min)

  36. Safety and tolerability of PF-06412562 assessed by vital signs

    Time frame: X2 on Day 4

    temperature (F)

  37. Safety and tolerability of PF-06412562 assessed by cardiology testing/cardiac autonomic function

    Time frame: X1 on Day 1 over 15 min

    Blood pressure (mmHg), cold pressor test measuring blood pressure (mmHg)

  38. Safety and tolerability of PF-06412562 assessed by cardiology testing/cardiac autonomic function

    Time frame: X1 on Day 1 over 15 min

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

  39. Safety and tolerability of PF-06412562 assessed by cardiology testing/cardiac autonomic function

    Time frame: X3 on Days 2 over 15 min each time

    Blood pressure (mmHg), cold pressor test measuring blood pressure (mmHg)

  40. Safety and tolerability of PF-06412562 assessed by cardiology testing/cardiac autonomic function

    Time frame: X3 on Days 2 over 15 min each time

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

  41. Safety and tolerability of PF-06412562 assessed by cardiology testing/cardiac autonomic function

    Time frame: X3 on Days 3 over 15 min each time

    Blood pressure (mmHg), cold pressor test measuring blood pressure (mmHg)

  42. Safety and tolerability of PF-06412562 assessed by cardiology testing/cardiac autonomic function

    Time frame: X3 on Days 3 over 15 min each time

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

  43. Safety and tolerability of PF-06412562 assessed by UPDRS-IV

    Time frame: X3 on Days 2

    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

  44. Safety and tolerability of PF-06412562 assessed by UPDRS-IV

    Time frame: X3 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

  45. Safety and tolerability of PF-06412562 assessed by Columbia Suicide Rating

    Time frame: X1 on Day 1

    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.

  46. Safety and tolerability of PF-06412562 assessed by Columbia Suicide Rating

    Time frame: X1 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.

Secondary outcomes

  1. 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

    Time frame: Global 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

Other outcomes

  1. Pilot data on potential efficacy of PF 06412562 on individual domains of alertness

    Time frame: Once before and X2 after drug administration on Days 2 & 3

    Glasgow Coma scale (GCS): records consciousness; each item rated 1-6; score range: 3-14, where 3=deep unconsciousness, 15=totally alert Stanford Sleepiness Scale (SSS): measure of alertness; rated 1-7, 1=fully alert, 7=almost asleep, min total score=1, max total score=7

  2. Pilot data on potential efficacy of PF 06412562 on individual domains of cogitation

    Time frame: Once before and X2 after drug administration on Days 2 & 3

    a. Severe Impairment Battery (SIB): evaluates cognition; min total score=0, max total score=100, higher score=lower cognition COGNISTAT: cognitive screening that assesses different domains of cognition Frontal Assessment Battery (FAB): used to assess different types of dementias. Min total score=0, max total score=18, higher scores=better performance

  3. Pilot data on potential efficacy of PF 06412562 on individual domains of motor

    Time frame: Once before and X2 after drug administration on Days 2 & 3

    MDS-UPDRS-motor (III) (United Parkinson's Disease Rating Scale): each question scored on scale of 0 to 4, where 0= not present, 4= severe; min total score:0, max total score:81; higher score corresponds to increased disease severity

  4. Pilot data on potential efficacy of PF 06412562 on individual domains of sleep

    Time frame: PSG sleep study: Days 1-3 at bedtime

    8 hour overnight polysomnography (PSG): sleep study monitoring body functions, brain activity (EEG), eye movements (EOG), muscle activity (EMG), and heart rhythm (ECG) Qualitative caregiver interview: (see outcome 2 description)

Sponsors and collaborators

Lead sponsor

Milton S. Hershey Medical Center

Other

Collaborators

  • Pfizer

Registry information

Official study 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

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Sep 11, 2018
Registry last updated
Jul 31, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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