PET Study in Parkinson's Disease Patients

Study Overview
=================
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

Official Title
-----------------
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

Conditions
-----------------
Parkinson's Disease

Intervention / Treatment
-----------------
* Drug: ER tablet 25 mg AZD3241
* Drug: ER tablet 100 mg AZD3241
* Drug: Placebo for AZD3241 25 mg
* Drug: Placebo for AZD3241 100 mg


Participation Criteria
=================
Eligibility Criteria
-----------------
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;

Ages Eligible for Study
-----------------
Minimum Age: 45 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD3241<br>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 | Drug: ER tablet 25 mg AZD3241<br>* 2 tablets twice daily for Day 1<br>Drug: ER tablet 100 mg AZD3241<br>* 1-6 tablets twice daily from Day 2 until Day 56±3 days<br>|
| Experimental: Placebo<br>AZD3241 placebo bid for 8 weeks | Drug: Placebo for AZD3241 25 mg<br>* 2 tablets twice daily for Day 1<br>Drug: Placebo for AZD3241 100 mg<br>* 1-6 tablets twice daily from Day 2 until Day 56±3 days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Phase IIa, AZD3241, microglia activation, safety, Pharmacodynamics and pharmacokinetics analyses, Parkinson patients