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AZD3241 PET MSA Trial, Phase 2, Randomized,12 Week Safety and Tolerability Trial With PET in MSA Patients

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ClinicalTrials.gov Identifier: NCT02388295
Recruitment Status : Completed
First Posted : March 17, 2015
Results First Posted : September 25, 2017
Last Update Posted : September 25, 2017
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
AZD3241 myeloperoxidase (MPO) inhibitor trial is assessing safety and tolerability, randomized trial, in patients with Multiple System Atrophy.

Condition or disease Intervention/treatment Phase
Multiple System Atrophy, MSA Drug: AZD3241 Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 59 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 12-Week, Multicenter, Randomized, Parallel-Group Study to Assess the Safety, Tolerability, Pharmacokinetics, Biomarker Effects, Efficacy, and Effect on Microglia Activation, as Measured by Positron Emission Tomography, of AZD3241 in Subjects With Multiple System Atrophy
Actual Study Start Date : April 27, 2015
Actual Primary Completion Date : September 19, 2016
Actual Study Completion Date : September 19, 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: AZD3241
Subjects will be randomized to one of the two doses of AZD3241 or placebo in a 1:1:1 ratio.
Drug: AZD3241
Drug: AZD3241 administered for 12 weeks orally as a tablet.
Other Name: AZD3241 to match placebo administered for 12 weeks.

Placebo Comparator: Placebo to match AZD3241
Subjects will be randomized to one of the two doses of AZD3241 or placebo in a 1:1:1 ratio.
Drug: Placebo
Placebo to match AZD3241 administered for 12 weeks orally as a tablet.
Other Name: Placebo to match AZD3241 administered for 12 weeks.




Primary Outcome Measures :
  1. Striatum Brain Region: Change From Baseline in Microglia Activation Via Positron Emission Tomography(PET) [ Time Frame: Baseline (pre randomization) and Week 12 ]
    Striatum Brain region: Change from baseline in microglia activation via PET By [11C]PBR28 binding to translocator protein


Secondary Outcome Measures :
  1. Myeloperoxidase (MPO) Inhibition in Plasma (Change From Baseline), Specific Activity [ Time Frame: Baseline (Day -1) and week 12 ]
    Myeloperoxidase (MPO) inhibition in plasma (change from baseline), on samples collected and analyzed, specific activity (activity/protein)


Other Outcome Measures:
  1. Exploratory Efficacy: Unified Multiple System Atropy Rating Scale, Change From Baseline (Total Score, Part 1 + Part 2) [ Time Frame: Baseline to final treatment visit ]
    Exploratory efficacy: Unified Multiple System Atropy Rating Scale, change from baseline (total Score, Part 1 + Part 2) : Score range 0 to 104, positive value indicates worsening symptoms



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Ages Eligible for Study:   30 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, age 30-80 years, inclusive, at screen.
  2. Meet criteria for diagnosis of probable or possible MSA according to the consensus criteria (Gilman et al. 2008 ).
  3. "High-affinity binder" or "mixed-affinity binder" for TSPO, as confirmed by prospective genotyping of TSPO polymorphism during screen.
  4. Subjects must understand the nature of the study and must provide signed and dated written informed consent in accordance with local regulations before the conduct of any study-related procedures. The informed consent should reflect the protocol stipulations concerning the use of contraception.
  5. Medical treatment of MSA and co-morbid medical conditions must be stable for at least 30 days prior to screen and between screen and baseline.
  6. Written and oral fluency in the local language.
  7. Able and willing to participate in all scheduled evaluations, abide by all study restrictions, and complete all required tests and procedures.
  8. In the opinion of the investigator, the subject must be considered likely to comply with the study protocol and to have a high probability of completing the study.
  9. Able to swallow tablets whole.

Exclusion Criteria:

  1. Prior participation in any AZD3241 study.
  2. Magnetic resonance imaging (MRI) performed during screen not consistent with diagnosis of MSA.
  3. Received a PET scan within the last 12 months.
  4. Negative Allen test in both hands, unless the brachial artery is used for arterial cannulation.
  5. Subjects determined to be "low affinity binders" by TSPO genotyping.
  6. Claustrophobia that would contraindicate a brain MRI scan or brain PET scan.
  7. Pregnancy, lactation, or, if female of childbearing potential, positive serum β-hCG at screen or positive urine β-hCG at baseline (Day -1).
  8. Initiation or change in pharmacologic therapy for symptoms of MSA within 30 days prior to screen or between screen and baseline (Day -1).
  9. Significant neurological disease affecting the central nervous system (CNS), other than MSA
  10. History of brain surgery for parkinsonism.
  11. History of stem cell treatment.
  12. Seizure disorder, unless well controlled and for which treatment has been stable for at least 30 days prior to screen and between screen and baseline (Day -1).
  13. Presence of any clinically significant medical condition
  14. History or presence of thyroid disease.
  15. Any abnormal TSH or Free T4 test result at screen or baseline (Day -1).
  16. History or presence of gastrointestinal disorders or other disease known to interfere with absorption, distribution, metabolism or excretion of drugs
  17. History or presence of renal disease or impaired renal function.
  18. A QT interval corrected according to the Fridericia procedure (QTcF) interval measurement > 450 msec at screen (single ECG) or baseline (Day -1) (mean of three ECG measurements) or a family history of long-QT syndrome.
  19. Uncontrolled hypertension
  20. History or presence of diabetes, unless glucose levels have been well controlled and for which treatment has been stable for at least 30 days prior to screen and between screen and baseline (Day -1).
  21. History of cancer within the last 5 years, with the exception of nonmetastatic basal cell carcinoma of the skin.
  22. Any clinically important abnormality, as determined by the investigator, on physical examination or vital signs, ECG, or clinical laboratory test results other than abnormality due to a stable, well-controlled medical condition; or any abnormality that could be detrimental to the subject or could compromise the study.
  23. Use of potent inhibitors of CYP3A4, Use of potent inducers of CYP3A4 and/or Use of drugs mainly metabolized by CYP3A4
  24. Treatment with any investigational drug or device within 60 days or five half-lives prior to screen, whichever is longer, or between screen and baseline (Day -1).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02388295


Locations
United States, California
Research Site
Stanford, California, United States, 94305
United States, Connecticut
Research Site
New Haven, Connecticut, United States, 06520-8048
United States, Florida
Research Site
Tampa, Florida, United States, 33613
United States, Massachusetts
Research Site
Boston, Massachusetts, United States, 02215
United States, Michigan
Research Site
Ann Arbor, Michigan, United States, 48105-2945
United States, Minnesota
Research Site
Rochester, Minnesota, United States, 55905
United States, New York
Research Site
New York, New York, United States, 10016
Research Site
New York, New York, United States, 10032
Austria
Research Site
Innsbruck, Austria, 6020
Finland
Research Site
Turku, Finland, 20520
France
Research Site
Bordeaux Cedex, France, 33076
Research Site
Toulouse Cedex 9, France, 31059
Italy
Research Site
Salerno, Italy, 84131
Sweden
Research Site
Stockholm, Sweden, 141 86
United Kingdom
Research Site
London, United Kingdom, SE5 9RJ
Research Site
London, United Kingdom, W12 0NN
Research Site
Oxford, United Kingdom, OX3 9DU
Sponsors and Collaborators
AstraZeneca

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02388295     History of Changes
Other Study ID Numbers: D0490C00023
First Posted: March 17, 2015    Key Record Dates
Results First Posted: September 25, 2017
Last Update Posted: September 25, 2017
Last Verified: July 2017

Keywords provided by AstraZeneca:
Multiple System Atrophy (MSA), PET imaging, myeloperoxidase (MPO) inhibitor

Additional relevant MeSH terms:
Atrophy
Multiple System Atrophy
Shy-Drager Syndrome
Pathological Conditions, Anatomical
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Hypotension
Vascular Diseases
Cardiovascular Diseases