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Trial record 1 of 1 for:    NCT03665454
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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

Tracking Information
First Submitted Date  ICMJE August 1, 2018
First Posted Date  ICMJE September 11, 2018
Last Update Posted Date July 31, 2019
Actual Study Start Date  ICMJE September 24, 2018
Actual Primary Completion Date March 21, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 7, 2018)
  • Safety and tolerability of PF-06412562 assessed by blood sample results [ Time Frame: Day 1 ]
    NA (mmol/L), K(mmol/L), HCO3(mmol/L)
  • 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)
  • Safety and tolerability of PF-06412562 assessed by blood sample results [ Time Frame: Day 1 ]
    AST (U/L), ALT (U/L)
  • Safety and tolerability of PF-06412562 assessed by blood sample results [ Time Frame: Day 1 ]
    white blood cell count (K/uL), platelets (K/uL)
  • Safety and tolerability of PF-06412562 assessed by blood sample results [ Time Frame: Day 1 ]
    Hematocrit (%)
  • Safety and tolerability of PF-06412562 assessed by blood sample results [ Time Frame: Day 1 ]
    hemoglobin (g/dL)
  • Safety and tolerability of PF-06412562 assessed by blood sample results [ Time Frame: Day 4 ]
    NA (mmol/L), K(mmol/L), HCO3(mmol/L)
  • 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)
  • Safety and tolerability of PF-06412562 assessed by blood sample results [ Time Frame: Day 4 ]
    AST (U/L), ALT (U/L)
  • Safety and tolerability of PF-06412562 assessed by blood sample results [ Time Frame: Day 4 ]
    white blood cell count (K/uL), platelets (K/uL)
  • Safety and tolerability of PF-06412562 assessed by blood sample results [ Time Frame: Day 4 ]
    hematocrit (%)
  • Safety and tolerability of PF-06412562 assessed by blood sample results [ Time Frame: Day 4 ]
    hemoglobin (g/dL)
  • Safety and tolerability of PF-06412562 assessed by blood sample results [ Time Frame: Day 4 ]
    Red blood cell count (M/uL)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: Time Frame: Vital signs: X2 on Day 1 ]
    height (inches)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X2 on Day 1 ]
    weight (lbs)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X2 on Day 1 ]
    blood pressure (mmHg)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X2 on Day 1 ]
    heart rate (bpm)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X2 on Day 1 ]
    respiratory rate (breathes/min)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X2 on Day 1 ]
    temperature (F)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X3 on Days 2 ]
    height (inches)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X3 on Days 2 ]
    blood pressure (mmHg)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X3 on Days 2 ]
    heart rate (bpm)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X3 on Days 2 ]
    respiratory rate (breathes/min)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X3 on Days 2 ]
    temperature (F)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X3 on Days 3 ]
    height (inches)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X3 on Days 3 ]
    weight (lbs)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X3 on Days 3 ]
    blood pressure (mmHg)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X3 on Days 3 ]
    heart rate (bpm)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X3 on Days 3 ]
    respiratory rate (breathes/min)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X3 on Days 3 ]
    temperature (F)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X2 on Day 4 ]
    height (inches)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X2 on Day 4 ]
    weight (lbs)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X2 on Day 4 ]
    blood pressure (mmHg)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X2 on Day 4 ]
    heart rate (bpm)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X2 on Day 4 ]
    respiratory rate (breathes/min)
  • Safety and tolerability of PF-06412562 assessed by vital signs [ Time Frame: X2 on Day 4 ]
    temperature (F)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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
  • 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
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2018)
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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 7, 2018)
  • 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
  • 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
  • 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
  • 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)
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE PF 06412562 in Subjects With Advanced Stage Parkinson's Disease
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE 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
Condition  ICMJE Parkinson Disease
Intervention  ICMJE
  • 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.
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: PF-06412562
  • 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.
    Intervention: Drug: Standard of Care Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 7, 2018)
8
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 21, 2019
Actual Primary Completion Date March 21, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03665454
Other Study ID Numbers  ICMJE 9437
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Xuemei Huang, MD, PhD, Milton S. Hershey Medical Center
Study Sponsor  ICMJE Milton S. Hershey Medical Center
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator: Xuemei Huang, MD, PhD Milton S. Hershey Medical Center
PRS Account Milton S. Hershey Medical Center
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP