PF 06412562 in Subjects With Advanced Stage Parkinson's Disease

NCT03665454 | Completed Phase 1 FDA Drug

• 1 other identifier: 9437
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson Disease

Keywords

Parkinson's Disease; Parkinson Disease; End-Stage; Progressed; Advanced Parkinson's Disease; End-Stage Parkinson's Disease; Clinical intervention; Double-blind, randomized

Outcome Measures

Primary Outcomes (46)

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

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

  Day 1

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

  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

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

  Day 1

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

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

  Day 1

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

  Hematocrit (%)

  Day 1

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

  hemoglobin (g/dL)

  Day 1

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

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

  Day 4

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

  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

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

  Day 4

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

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

  Day 4

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

  hematocrit (%)

  Day 4

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

  hemoglobin (g/dL)

  Day 4

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

  Red blood cell count (M/uL)

  Day 4

• Safety and tolerability of PF-06412562 assessed by vital signs

  height (inches)

  Time Frame: Vital signs: X2 on Day 1

• Safety and tolerability of PF-06412562 assessed by vital signs

  weight (lbs)

  X2 on Day 1

• Safety and tolerability of PF-06412562 assessed by vital signs

  blood pressure (mmHg)

  X2 on Day 1

• Safety and tolerability of PF-06412562 assessed by vital signs

  heart rate (bpm)

  X2 on Day 1

• Safety and tolerability of PF-06412562 assessed by vital signs

  respiratory rate (breathes/min)

  X2 on Day 1

• Safety and tolerability of PF-06412562 assessed by vital signs

  temperature (F)

  X2 on Day 1

• Safety and tolerability of PF-06412562 assessed by vital signs

  height (inches)

  X3 on Days 2

• Safety and tolerability of PF-06412562 assessed by vital signs

  blood pressure (mmHg)

  X3 on Days 2

• Safety and tolerability of PF-06412562 assessed by vital signs

  heart rate (bpm)

  X3 on Days 2

• Safety and tolerability of PF-06412562 assessed by vital signs

  respiratory rate (breathes/min)

  X3 on Days 2

• Safety and tolerability of PF-06412562 assessed by vital signs

  temperature (F)

  X3 on Days 2

• Safety and tolerability of PF-06412562 assessed by vital signs

  height (inches)

  X3 on Days 3

• Safety and tolerability of PF-06412562 assessed by vital signs

  weight (lbs)

  X3 on Days 3

• Safety and tolerability of PF-06412562 assessed by vital signs

  blood pressure (mmHg)

  X3 on Days 3

• Safety and tolerability of PF-06412562 assessed by vital signs

  heart rate (bpm)

  X3 on Days 3

• Safety and tolerability of PF-06412562 assessed by vital signs

  respiratory rate (breathes/min)

  X3 on Days 3

• Safety and tolerability of PF-06412562 assessed by vital signs

  temperature (F)

  X3 on Days 3

• Safety and tolerability of PF-06412562 assessed by vital signs

  height (inches)

  X2 on Day 4

• Safety and tolerability of PF-06412562 assessed by vital signs

  weight (lbs)

  X2 on Day 4

• Safety and tolerability of PF-06412562 assessed by vital signs

  blood pressure (mmHg)

  X2 on Day 4

• Safety and tolerability of PF-06412562 assessed by vital signs

  heart rate (bpm)

  X2 on Day 4

• Safety and tolerability of PF-06412562 assessed by vital signs

  respiratory rate (breathes/min)

  X2 on Day 4

• Safety and tolerability of PF-06412562 assessed by vital signs

  temperature (F)

  X2 on Day 4

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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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 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

  Global Impression of Change: X3 on Days 2 and 3; Caregiver Perception of Change: X1 on Day 3

Other Outcomes (4)

• Pilot data on potential efficacy of PF 06412562 on individual domains of alertness

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

• Pilot data on potential efficacy of PF 06412562 on individual domains of cogitation

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

• Pilot data on potential efficacy of PF 06412562 on individual domains of motor

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

Study Arms (2)

PF-06412562

EXPERIMENTAL

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

Standard of Care carbidopa/levodopa

ACTIVE COMPARATOR

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

Interventions

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.

PF-06412562

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.

Also known as: Sinemet

Standard of Care carbidopa/levodopa

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• Pfizer: collaborator

Study Sites (1)

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Related Publications (2)

• Fernandez-Mendoza J, Puzino K, Amatrudo G, Bourchtein E, Calhoun SL, Plante DT, Kaplan K. The Hypersomnia Severity Index: reliability, construct, and criterion validity in a clinical sample of patients with sleep disorders. J Clin Sleep Med. 2021 Nov 1;17(11):2249-2256. doi: 10.5664/jcsm.9426.

  PMID: 34032202 DERIVED

• Huang X, Lewis MM, Van Scoy LJ, De Jesus S, Eslinger PJ, Arnold AC, Miller AJ, Fernandez-Mendoza J, Snyder B, Harrington W, Kong L, Wang X, Sun D, Delnomdedieu M, Duvvuri S, Mahoney SE, Gray DL, Mailman RB. The D1/D5 Dopamine Partial Agonist PF-06412562 in Advanced-Stage Parkinson's Disease: A Feasibility Study. J Parkinsons Dis. 2020;10(4):1515-1527. doi: 10.3233/JPD-202188.

  PMID: 32986682 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Interventions

carbidopa, levodopa drug combination

Condition Hierarchy (Ancestors)

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

Study Officials

• Xuemei Huang, MD, PhD

  Milton S. Hershey Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Neurology

Model Details: 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.

Study Record Dates

• First Submitted: August 1, 2018
• First Posted: September 11, 2018
• Study Start: September 24, 2018
• Primary Completion: March 21, 2019
• Study Completion: April 21, 2019
• Last Updated: July 31, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)