Parkinson's Disease
Conditions
Keywords
Phase IIa, AZD3241, microglia activation, safety, Pharmacodynamics and pharmacokinetics analyses, Parkinson patients
Brief summary
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.
Detailed description
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
Interventions
DRUGER tablet 25 mg AZD3241
2 tablets twice daily for Day 1
DRUGER tablet 100 mg AZD3241
1-6 tablets twice daily from Day 2 until Day 56±3 days
DRUGPlacebo for AZD3241 25 mg
2 tablets twice daily for Day 1
DRUGPlacebo for AZD3241 100 mg
1-6 tablets twice daily from Day 2 until Day 56±3 days
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change of binding [11C]PBR28 to translocator protein (TSPO) measured by Positron Emission Tomography (PET). | baseline, 2-4 weeks |
| Change of binding of [11C]PBR28 to TSPO measured by PET. | baseline, 7-8 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Adverse events, vital signs, electrocardiogram (ECG), physical examination, clinical chemistry tests, height and weight measures for safety and tolerability profile. | Up to 10 weeks |
| Change in plasma activity of myeloperoxidase (MPO). | baseline, up to 10 weeks |
| Plasma concentrations of AZD3241. | Up to 8 weeks |
| Part of safety profile in terms of Columbia Suicide Severity Rating Scale. | Up to 10 weeks |
Countries
Sweden
Outcome results
None listed