PF 06412562 in Subjects With Advanced Stage Parkinson's Disease

July 30, 2019 updated by: Xuemei Huang, MD, PhD, Milton S. Hershey Medical Center

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
8

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Milton S. Hershey Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • Sinemet

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety and tolerability of PF-06412562 assessed by blood sample results
Time Frame: Day 1
NA (mmol/L), K(mmol/L), HCO3(mmol/L)
Day 1
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)
Day 1
Safety and tolerability of PF-06412562 assessed by blood sample results
Time Frame: Day 1
AST (U/L), ALT (U/L)
Day 1
Safety and tolerability of PF-06412562 assessed by blood sample results
Time Frame: Day 1
white blood cell count (K/uL), platelets (K/uL)
Day 1
Safety and tolerability of PF-06412562 assessed by blood sample results
Time Frame: Day 1
Hematocrit (%)
Day 1
Safety and tolerability of PF-06412562 assessed by blood sample results
Time Frame: Day 1
hemoglobin (g/dL)
Day 1
Safety and tolerability of PF-06412562 assessed by blood sample results
Time Frame: Day 4
NA (mmol/L), K(mmol/L), HCO3(mmol/L)
Day 4
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)
Day 4
Safety and tolerability of PF-06412562 assessed by blood sample results
Time Frame: Day 4
AST (U/L), ALT (U/L)
Day 4
Safety and tolerability of PF-06412562 assessed by blood sample results
Time Frame: Day 4
white blood cell count (K/uL), platelets (K/uL)
Day 4
Safety and tolerability of PF-06412562 assessed by blood sample results
Time Frame: Day 4
hematocrit (%)
Day 4
Safety and tolerability of PF-06412562 assessed by blood sample results
Time Frame: Day 4
hemoglobin (g/dL)
Day 4
Safety and tolerability of PF-06412562 assessed by blood sample results
Time Frame: Day 4
Red blood cell count (M/uL)
Day 4
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: Time Frame: Vital signs: X2 on Day 1
height (inches)
Time Frame: Vital signs: X2 on Day 1
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X2 on Day 1
weight (lbs)
X2 on Day 1
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X2 on Day 1
blood pressure (mmHg)
X2 on Day 1
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X2 on Day 1
heart rate (bpm)
X2 on Day 1
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X2 on Day 1
respiratory rate (breathes/min)
X2 on Day 1
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X2 on Day 1
temperature (F)
X2 on Day 1
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X3 on Days 2
height (inches)
X3 on Days 2
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X3 on Days 2
blood pressure (mmHg)
X3 on Days 2
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X3 on Days 2
heart rate (bpm)
X3 on Days 2
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X3 on Days 2
respiratory rate (breathes/min)
X3 on Days 2
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X3 on Days 2
temperature (F)
X3 on Days 2
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X3 on Days 3
height (inches)
X3 on Days 3
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X3 on Days 3
weight (lbs)
X3 on Days 3
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X3 on Days 3
blood pressure (mmHg)
X3 on Days 3
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X3 on Days 3
heart rate (bpm)
X3 on Days 3
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X3 on Days 3
respiratory rate (breathes/min)
X3 on Days 3
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X3 on Days 3
temperature (F)
X3 on Days 3
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X2 on Day 4
height (inches)
X2 on Day 4
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X2 on Day 4
weight (lbs)
X2 on Day 4
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X2 on Day 4
blood pressure (mmHg)
X2 on Day 4
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X2 on Day 4
heart rate (bpm)
X2 on Day 4
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X2 on Day 4
respiratory rate (breathes/min)
X2 on Day 4
Safety and tolerability of PF-06412562 assessed by vital signs
Time Frame: X2 on Day 4
temperature (F)
X2 on Day 4
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)
X1 on Day 1 over 15 min
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)
X1 on Day 1 over 15 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)
X3 on Days 2 over 15 min each time
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)
X3 on Days 2 over 15 min each time
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)
X3 on Days 3 over 15 min each time
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)
X3 on Days 3 over 15 min each time
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
X3 on Days 2
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
X3 on Days 3
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.
X1 on Day 1
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.
X1 on Day 4

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Global Impression of Change: X3 on Days 2 and 3; Caregiver Perception of Change: X1 on Day 3

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Once before and X2 after drug administration on Days 2 & 3
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
Once before and X2 after drug administration on Days 2 & 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
Once before and X2 after drug administration on Days 2 & 3
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)
PSG sleep study: Days 1-3 at bedtime

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Milton S. Hershey Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Pfizer

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Xuemei Huang, MD, PhD, Milton S. Hershey Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 24, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 21, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 21, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 1, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 7, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 11, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 31, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 30, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 9437

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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