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PF 06412562 in Subjects With Advanced Stage Parkinson's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03665454
Recruitment Status : Completed
First Posted : September 11, 2018
Last Update Posted : July 31, 2019
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Xuemei Huang, MD, PhD, 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.

Condition or disease Intervention/treatment Phase
Parkinson Disease Drug: PF-06412562 Drug: Standard of Care Placebo Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Investigational Drug Services, which is the investigational drug pharmacy at Hershey Medical Center, will be preparing and dispensing the drug. They will be the only party that is unblinded. Pfizer will provide placebo pills that are identical in appearance to the PF-06412562 study drug. The standard of care treatment, carbidopa/levodopa, is different in appearance to PF-06412562 and its corresponding matching placebo. In order to blind for this, Investigational Drug Services will encapsulate the carbidopa/levodopa pills. Thus, subjects may receive either an encapsulated carbidopa/levodopa pill or an empty non-active capsule, depending on the treatment arm and dosing they are scheduled to receive.
Primary Purpose: Treatment
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
Actual Study Start Date : September 24, 2018
Actual Primary Completion Date : March 21, 2019
Actual Study Completion Date : April 21, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PF-06412562
Subjects 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.
Drug: PF-06412562
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.

Active Comparator: Standard of Care carbidopa/levodopa
Subjects 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.
Drug: Standard of Care Placebo
25/100 mg tablet(s) of carbidopa/levodopa will be encapsulated and administered according to the subject's home regimen.
Other Name: Sinemet




Primary Outcome Measures :
  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 Outcome Measures :
  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 Outcome Measures:
  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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03665454


Locations
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United States, Pennsylvania
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Sponsors and Collaborators
Milton S. Hershey Medical Center
Pfizer
Investigators
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Principal Investigator: Xuemei Huang, MD, PhD Milton S. Hershey Medical Center

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Responsible Party: Xuemei Huang, MD, PhD, Professor, Department of Neurology, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT03665454     History of Changes
Other Study ID Numbers: 9437
First Posted: September 11, 2018    Key Record Dates
Last Update Posted: July 31, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Xuemei Huang, MD, PhD, Milton S. Hershey Medical Center:
Parkinson's Disease
Parkinson Disease
End-Stage
Progressed
Advanced Parkinson's Disease
End-Stage Parkinson's Disease
Clinical intervention
Double-blind, randomized

Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Levodopa
Carbidopa
Carbidopa, levodopa drug combination
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Aromatic Amino Acid Decarboxylase Inhibitors
Enzyme Inhibitors
Adjuvants, Immunologic
Immunologic Factors
Dopamine Agonists