Clinical trial NCT01527695: PET Study in Parkinson's Disease Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson's Disease
Keywords: Phase IIa
AZD3241
microglia activation
safety
Pharmacodynamics and pharmacokinetics analyses
Parkinson patients
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2012-02-07
Enrollment: 24
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

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;

Primary outcomes:
measure: Change of binding [11C]PBR28 to translocator protein (TSPO) measured by Positron Emission Tomography (PET).
timeFrame: baseline, 2-4 weeks
measure: Change of binding of [11C]PBR28 to TSPO measured by PET.
timeFrame: baseline, 7-8 weeks
Secondary outcomes:
measure: Adverse events, vital signs, electrocardiogram (ECG), physical examination, clinical chemistry tests, height and weight measures for safety and tolerability profile.
timeFrame: Up to 10 weeks
measure: Change in plasma activity of myeloperoxidase (MPO).
timeFrame: baseline, up to 10 weeks
measure: Plasma concentrations of AZD3241.
timeFrame: Up to 8 weeks
measure: Part of safety profile in terms of Columbia Suicide Severity Rating Scale.
timeFrame: Up to 10 weeks
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Reserach Site
city: Uppsala
country: Sweden
facility: Research Site
city: Vallingby
country: Sweden
facility: Research Site
Study officials:
affiliation: Karolinska University Hospital
name: Per Svenningsson, MD, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca Medical Science Director
name: Bjorn Paulsson, MD
role: STUDY_DIRECTOR
References: