A PHASE 2 MULTICENTER, RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED STUDY OF THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF MULTIPLE DOSES OF PF 04360365 IN PATIENTS WITH MILD TO MODERATE ALZHEIMER'S DISEASE.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 198
- 试验地点
- 41
- 主要终点
- Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 60
研究概览
简要总结
Purpose of the study is to determine whether multiple dose administration of PF-04360365 is safe and well tolerated in patient with mild to moderate Alzheimer's disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females of non childbearing potential, age > or = 50
- •Diagnosis of probable Alzheimer's disease, consistent with criterial from both:
- •National Institute of Neurological and Communicable Disease and Stroke and Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA)
- •Diagnostic and Statistical Manual of Mental Disorders (DSM IV)
- •Mini-mental status exam score of 16-26 inclusive
- •Rosen-Modified Hachinski Ischemia Score of < or = 4
排除标准
- •Diagnosis or history of other demential or neurodegenerative disorders
- •Diagnosis or history of clinically significant cerebrovascular disease
- •Specific findings on magnetic resonance imaging (MRI); cortical infarct, micro hemorrhage, multiple white matter lacunes, extensive white matter abnormalities
- •History of autoimmune disorders
- •History of allergic or anaphylactic reactions
研究组 & 干预措施
PF-04360365 3 mg/kg
干预措施: PF-04360365 3 mg/kg (Biological)
PF-04360365 0.1 mg/kg
干预措施: PF-04360365 0.1 mg/kg (Biological)
PF-04360365 0.5 mg/kg
干预措施: PF-04360365 0.5 mg/kg (Biological)
PF-04360365 1 mg/kg
干预措施: PF-04360365 1 mg/kg (Biological)
Placebo
干预措施: Placebo (Drug)
PF-04360365 8.5 mg/kg
干预措施: PF-04360365 8.5 mg/kg (Biological)
结局指标
主要结局
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 60
时间窗: 0 Hour (pre-dose) on Day 60
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 90
时间窗: Day 90
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 on Day 150
时间窗: Day 150
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 240
时间窗: 2 Hours on Day 240
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 300
时间窗: 0 Hour (pre-dose) on Day 300
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 300
时间窗: 2 Hours on Day 300
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 360
时间窗: 0 Hour (pre-dose) on Day 360
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 360
时间窗: 2 Hours on Day 360
Only participants received PF-04360365 were analyzed for this outcome measure.
Number of Participants With Gadolinium Use in Brain Magnetic Resonance Imaging (MRI)
时间窗: Baseline up to Month 24
Brain MRI included gadolinium contrast if investigator determined this was necessary for participant care either based on clinical signs or the non-contrast MRI. This decision was made by the investigator on the basis of change in the clinical examination or in response to a possible abnormality seen on the non-contrast brain MRI. Baseline was defined as the last assessment prior to the first study drug infusion.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 60
时间窗: 2 Hours on Day 60
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 on Day 210
时间窗: Day 210
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 240
时间窗: 0 Hour (pre-dose) on Day 240
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 on Day 660
时间窗: Day 660
Only participants received PF-04360365 were analyzed for this outcome measure.
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
时间窗: Day 1 up to 6 months after last dose of study medication, assessed up to Month 24
An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. SAE: an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events between first dose of study medication and up to 6 months after last dose that were absent before treatment or worsened relative to pre-treatment state.
Number of Participants With Change From Baseline in Brain Magnetic Resonance Imaging (MRI) Abnormalities
时间窗: Baseline up to Month 24
Number of participants with new clinical findings not evident on the baseline scans, such as brain edema, hemorrhage, encephalitis and other pathology (cerebral/meningeal enhancement, parenchymal hematoma, subarachnoid hemorrhage, subdural hematoma, cortical infarcts, subcortical grey matter infarcts, white matter infarcts and white matter hyperintensities) were assessed from structural MRI. Participants with brain abnormality other than those listed above, assessed using MRI scan, were reported under other abnormality. Baseline was defined as the last assessment prior to the first study drug infusion.
Mean Cerebrospinal Fluid (CSF) Concentration of PF-04360365 at 0 Hour on Day 0
时间窗: 0 Hour on Day 0
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 1
时间窗: 0 Hour (pre-dose) on Day 1
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 1
时间窗: 2 Hours on Day 1
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 120
时间窗: 0 Hour (pre-dose) on Day 120
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 120
时间窗: 2 Hours on Day 120
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 180
时间窗: 0 Hour (pre-dose) on Day 180
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 180
时间窗: 2 Hours on Day 180
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 on Day 390
时间窗: Day 390
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 420
时间窗: 0 Hour (pre-dose) on Day 420
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 420
时间窗: 2 Hours on Day 420
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 480
时间窗: 0 Hour (pre-dose) on Day 480
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 480
时间窗: 2 Hours on Day 480
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 0 Hour on Day 540
时间窗: 0 Hour (pre-dose) on Day 540
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 at 2 Hours on Day 540
时间窗: 2 Hours on Day 540
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma and Cerebrospinal Fluid (CSF) Concentration of PF-04360365 on Day 570
时间窗: Day 570
Only participants received PF-04360365 were analyzed for this outcome measure.
Mean Plasma Concentration of PF-04360365 on Day 720
时间窗: Day 720
Only participants received PF-04360365 were analyzed for this outcome measure.
次要结局
- Mean Plasma Concentration of Amyloid Beta 1-40 (Aβ1-40)(0 Hour (pre-dose) and 2 hours on Day 1, 60, 120, 180, 240, 300, 360, 420, 480, 540; Day 90, 150, 210, 390, 570, 660, 720)
- Mean Plasma Concentration of Amyloid Beta 1-42 (Aβ1-42)(0 Hour (pre-dose) and 2 hours on Day 1, 60, 120, 180, 240, 300, 360, 420, 480, 540; Day 90, 150, 210, 390, 570, 660, 720)
- Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-x (Aβ1-x)(Day 0 (Hour 0), 90, 570)
- Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-40 (Aβ1-40)(Day 0 (Hour 0), 90, 570)
- Mean Cerebrospinal Fluid (CSF) Concentration of Amyloid Beta 1-42 (Aβ1-42)(Day 0 (Hour 0), 90, 570)
- Mean Cerebrospinal Fluid (CSF) Concentration of Total Tau and Phospho-tau (P-tau)(Day 0 (Hour 0), 90, 570)
- Number of Participants With Abnormal Cerebrospinal Fluid (CSF) Protein, Red Blood Cells (RBCs), White Blood Cells (WBCs), and Glucose Concentration(Baseline up to Month 24)
- Number of Participants With Serum Anti-Drug Anti Body (ADA)(Day 1 up to Month 24)
- Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) Score at Baseline(Baseline)
- Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) Score at Month 19(Baseline and Month 19)
- Disability Assessment for Dementia (DAD) Score at Baseline(Baseline)
- Change From Baseline in Disability Assessment for Dementia (DAD) Score at Month 19(Baseline and Month 19)
- Mean Plasma Concentration of Amyloid Beta 1-x (Aβ1-x)(0 Hour (pre-dose) and 2 hours on Day 1, 60, 120, 180, 240, 300, 360, 420, 480, 540; Day 90, 150, 210, 390, 570, 660, 720)