Parkinson Disease
Conditions
Keywords
Parkinson's Disease, Parkinson Disease, End-Stage, Progressed, Advanced Parkinson's Disease, End-Stage Parkinson's Disease, Clinical intervention, Double-blind, randomized
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.
Interventions
DRUGPF-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.
DRUGStandard of Care Placebo
25/100 mg tablet(s) of carbidopa/levodopa will be encapsulated and administered according to the subject's home regimen.
Sponsors
Pfizer
Milton S. Hershey Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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.
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.
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of PF-06412562 assessed by Columbia Suicide Rating | 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 blood sample results | Day 1 | NA (mmol/L), K(mmol/L), HCO3(mmol/L) |
| Safety and tolerability of PF-06412562 assessed by vital signs | Time Frame: Vital signs: X2 on Day 1 | height (inches) |
| Safety and tolerability of PF-06412562 assessed by cardiology testing/cardiac autonomic function | 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 UPDRS-IV | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | • 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
| Measure | Time frame | Description |
|---|---|---|
| Pilot data on potential efficacy of PF 06412562 on individual domains of alertness | 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 | 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 | 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 | 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) |
Countries
United States
Outcome results
None listed