PF 06412562 in Subjects With Advanced Stage Parkinson's Disease

Parkinson Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03665454
• Other study ID #: 9437
• Status: Completed
• Phase: Phase 1
• Start date: September 24, 2018
• Est. completion date: April 21, 2019

Study information

• Verified date: July 2019
• Source: Milton S. Hershey Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: April 21, 2019
• Est. primary completion date: March 21, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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)

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

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

Locations

Country	Name	City	State
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pilot data on potential efficacy of PF 06412562 on individual domains of alertness	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
Other	Pilot data on potential efficacy of PF 06412562 on individual domains of cogitation	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
Other	Pilot data on potential efficacy of PF 06412562 on individual domains of motor	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
Other	Pilot data on potential efficacy of PF 06412562 on individual domains of sleep	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
Primary	Safety and tolerability of PF-06412562 assessed by blood sample results	NA (mmol/L), K(mmol/L), HCO3(mmol/L)	Day 1
Primary	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
Primary	Safety and tolerability of PF-06412562 assessed by blood sample results	AST (U/L), ALT (U/L)	Day 1
Primary	Safety and tolerability of PF-06412562 assessed by blood sample results	white blood cell count (K/uL), platelets (K/uL)	Day 1
Primary	Safety and tolerability of PF-06412562 assessed by blood sample results	Hematocrit (%)	Day 1
Primary	Safety and tolerability of PF-06412562 assessed by blood sample results	hemoglobin (g/dL)	Day 1
Primary	Safety and tolerability of PF-06412562 assessed by blood sample results	NA (mmol/L), K(mmol/L), HCO3(mmol/L)	Day 4
Primary	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
Primary	Safety and tolerability of PF-06412562 assessed by blood sample results	AST (U/L), ALT (U/L)	Day 4
Primary	Safety and tolerability of PF-06412562 assessed by blood sample results	white blood cell count (K/uL), platelets (K/uL)	Day 4
Primary	Safety and tolerability of PF-06412562 assessed by blood sample results	hematocrit (%)	Day 4
Primary	Safety and tolerability of PF-06412562 assessed by blood sample results	hemoglobin (g/dL)	Day 4
Primary	Safety and tolerability of PF-06412562 assessed by blood sample results	Red blood cell count (M/uL)	Day 4
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	height (inches)	Time Frame: Vital signs: X2 on Day 1
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	weight (lbs)	X2 on Day 1
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	blood pressure (mmHg)	X2 on Day 1
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	heart rate (bpm)	X2 on Day 1
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	respiratory rate (breathes/min)	X2 on Day 1
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	temperature (F)	X2 on Day 1
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	height (inches)	X3 on Days 2
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	blood pressure (mmHg)	X3 on Days 2
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	heart rate (bpm)	X3 on Days 2
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	respiratory rate (breathes/min)	X3 on Days 2
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	temperature (F)	X3 on Days 2
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	height (inches)	X3 on Days 3
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	weight (lbs)	X3 on Days 3
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	blood pressure (mmHg)	X3 on Days 3
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	heart rate (bpm)	X3 on Days 3
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	respiratory rate (breathes/min)	X3 on Days 3
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	temperature (F)	X3 on Days 3
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	height (inches)	X2 on Day 4
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	weight (lbs)	X2 on Day 4
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	blood pressure (mmHg)	X2 on Day 4
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	heart rate (bpm)	X2 on Day 4
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	respiratory rate (breathes/min)	X2 on Day 4
Primary	Safety and tolerability of PF-06412562 assessed by vital signs	temperature (F)	X2 on Day 4
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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	• 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