A Phase IIA, Multi Centre, Double-blind, Randomised, Placebo-controlled, Parallel-group Study to Assess the Effect of 8 Weeks Treatment With Oral AZD3241 on Microglia Activation, as Measured by Positron Emission Tomography (PET), in Patients With Parkinson's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Change of binding of [11C]PBR28 to TSPO measured by PET.
研究概览
简要总结
This is a multi-centre study to be conducted in Sweden and Finland. Up to 24 male and/or female patients of non-childbearing potential aged 45 to 75 years (inclusive), with a clinical diagnosis Parkinson's Disease will be randomised in the study to allow for 20 patients to complete this study.The study will evaluate the effect of 8 weeks treatment with AZD3241 on microglia activation as measured via PET examinations.
详细描述
A Phase IIA, Multi centre, Double-blind, Randomised, Placebo-controlled, Parallel-group Study to Assess the Effect of 8 Weeks Treatment with Oral AZD3241 on Microglia Activation, as Measured by Positron Emission Tomography (PET), in Patients with Parkinson'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
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 45 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Female and male patients aged 45 to 75 years (inclusive) at the day of enrolment (Visit 1)
- •Female patients must have a negative pregnancy test at Screening, must not be lactating and must be of non childbearing potential, confirmed at Screening
- •Male patients should be willing to use barrier contraception, eg, condoms, even if their partners are post-menopausal, be surgically sterile or are using accepted contraceptive methods, from the administration of the first dose of the investigational
- •The clinical diagnosis of patients must meet the criteria for "diagnosis of idiopathic Parkinson's disease" according to the modified UKPDS Brain Bank criteria (see Appendix E)
- •Modified Hoehn and Yahr stage 1 to 2
排除标准
- •Diagnosis is unclear or a suspicion of other Parkinsonian syndromes exists, such as secondary Parkinsonism (caused by drugs, toxins, infectious agents, vascular disease, trauma, brain neoplasm), Parkinson-plus syndromes or heredodegenerative diseases
- •Patients who have undergone surgery for the treatment of Parkinson's disease (eg, pallidotomy, deep brain stimulation, foetal tissue transplantation) or have undergone any other brain surgery
- •Presence of significant dyskinesias, motor fluctuations, swallowing difficulties or loss of postural reflexes Patients with a history of non-response (according to both the clinician and the patient) to an adequate course of L-dopa or a DA agonist
- •Use of pergolide, selegiline, metoclopramide, strong CYP3A4 inhibitors, CYP3A4 inducers (including St John's Wort) and strong CYP1A2 inhibitors and inducers, within 1 month of randomisation;
研究组 & 干预措施
AZD3241
AZD3241 tablets 25 mg or 100 mg, titration first 5 days (50 mg bd on Day 1, 100 mg bd on Day 2, 200 mg bd on Day 3, 300 mg bd on Day 4, 400 mg bd on Day 5) Maintenance treatment from Day 6, 600 mg bd until Day 56±3 days
干预措施: ER tablet 25 mg AZD3241 (Drug)
AZD3241
AZD3241 tablets 25 mg or 100 mg, titration first 5 days (50 mg bd on Day 1, 100 mg bd on Day 2, 200 mg bd on Day 3, 300 mg bd on Day 4, 400 mg bd on Day 5) Maintenance treatment from Day 6, 600 mg bd until Day 56±3 days
干预措施: ER tablet 100 mg AZD3241 (Drug)
Placebo
AZD3241 placebo bid for 8 weeks
干预措施: Placebo for AZD3241 25 mg (Drug)
Placebo
AZD3241 placebo bid for 8 weeks
干预措施: Placebo for AZD3241 100 mg (Drug)
结局指标
主要结局
Change of binding of [11C]PBR28 to TSPO measured by PET.
时间窗: baseline, 7-8 weeks
Change of binding [11C]PBR28 to translocator protein (TSPO) measured by Positron Emission Tomography (PET).
时间窗: baseline, 2-4 weeks
次要结局
- Part of safety profile in terms of Columbia Suicide Severity Rating Scale.(Up to 10 weeks)
- Adverse events, vital signs, electrocardiogram (ECG), physical examination, clinical chemistry tests, height and weight measures for safety and tolerability profile.(Up to 10 weeks)
- Plasma concentrations of AZD3241.(Up to 8 weeks)
- Change in plasma activity of myeloperoxidase (MPO).(baseline, up to 10 weeks)