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

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).