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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Safety and tolerability of PF-06412562 assessed by blood sample results
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
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.
干预措施: PF-06412562 (Drug)
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.
干预措施: Standard of Care Placebo (Drug)
结局指标
主要结局
Safety and tolerability of PF-06412562 assessed by blood sample results
时间窗: Day 4
Red blood cell count (M/uL)
Safety and tolerability of PF-06412562 assessed by cardiology testing/cardiac autonomic function
时间窗: 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 Columbia Suicide Rating
时间窗: 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.
Safety and tolerability of PF-06412562 assessed by vital signs
时间窗: X2 on Day 4
temperature (F)
Safety and tolerability of PF-06412562 assessed by UPDRS-IV
时间窗: 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
次要结局
- 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)
研究者
Xuemei Huang, MD, PhD
Professor, Department of Neurology
Milton S. Hershey Medical Center