PET Study in Parkinson's Disease Patients

NCT01527695 | Completed Phase 2

• 1 other identifier: D0490C00004
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

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.

Conditions

Parkinson's Disease

Keywords

Phase IIa; AZD3241; microglia activation; safety; Pharmacodynamics and pharmacokinetics analyses; Parkinson patients

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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

Study Arms (2)

AZD3241

EXPERIMENTAL

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; Drug: ER tablet 100 mg AZD3241

Placebo

EXPERIMENTAL

AZD3241 placebo bid for 8 weeks

Drug: Placebo for AZD3241 25 mg; Drug: Placebo for AZD3241 100 mg

Interventions

ER tablet 25 mg AZD3241 DRUG

2 tablets twice daily for Day 1

AZD3241

ER tablet 100 mg AZD3241 DRUG

1-6 tablets twice daily from Day 2 until Day 56±3 days

AZD3241

Placebo for AZD3241 25 mg DRUG

2 tablets twice daily for Day 1

Placebo

Placebo for AZD3241 100 mg DRUG

1-6 tablets twice daily from Day 2 until Day 56±3 days

Placebo

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (3)

Reserach Site

Stockholm, Sweden

Location

Research Site

Uppsala, Sweden

Location

Research Site

Vällingby, Sweden

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

AZD3241

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Per Svenningsson, MD, PHD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

• Bjorn Paulsson, MD

  AstraZeneca Medical Science Director

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2011
• First Posted: February 7, 2012
• Study Start: April 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: January 1, 2013
• Last Updated: January 31, 2013

Record last verified: 2013-01

Locations

SE (3)