A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD7594 Inhaled Formulation in Healthy Japanese Men

This is a phase I, randomized, single-blind, placebo controlled, sequential-group design
study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of
AZD7594 after single and multiple ascending doses given once daily by inhalation in healthy
male Japanese subjects, compared with placebo

Inclusion Criteria:

1. Provision of signed and dated, written informed consent prior to any study specific
procedures.

2. Healthy male Japanese subjects aged 20 to 45 years with suitable veins for cannulation
or repeated venipuncture.

A Japanese male subject is defined as being born in Japan, having both parents and
four grandparents who are Japanese. The subject must not have lived outside of Japan
for more than 5 years.

3. Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 45
kg and no more than 100 kg inclusive.

4. Provision of signed, written and dated informed consent for optional genetic research
Note: If a subject declines to participate in the genetic component of the study,
there will be no penalty or loss of benefit to the subject. The subject will not be
excluded from other aspects of the study described in this protocol.

Exclusion Criteria:

1. History of any clinically significant disease or disorder which, in the opinion of the
investigator, may either put the subject at risk because of participation in the
study, or influence the results or the subject's ability to participate in the study.

2. History or presence of gastrointestinal (GI), hepatic or renal disease, or any other
condition known to interfere with absorption, distribution, metabolism, or excretion
of drugs.

3. Any clinically significant illness, medical/surgical procedure, or trauma within 4
weeks of the first administration of investigational drug administration.

4. Any contraindication against the use of vagolytic or sympaticomimetic drugs, as judged
by the investigator.

5. Any clinically significant abnormalities in clinical chemistry, hematology,
urinalysis, physical examination, vital signs, electrocardiogram (ECG) or lung
function results at baseline, as judged by the investigator.

6. Known Gilbert's syndrome, family history of Gilbert's syndrome or suspicion of
Gilbert's syndrome based on liver function tests.

7. Use of systemic glucocorticosteroids within 6 weeks of enrollment.

8. Any positive result on screening for serum hepatitis B surface antigen (HBsAg),
hepatitis C antibody and human immunodeficiency virus (HIV).

9. Known or suspected hypersensitivity to investigational product or excipients.

10. Plasma donation within one month of screening or any blood donation/blood loss > 500
mL during the 3 months prior to screening.

11. Abnormal vital signs, after 10 minutes supine rest, defined as any of the following:

- Systolic blood pressure (BP) < 90mmHg or > 140 mmHg

- Diastolic BP < 60mmHg or > 90 mmHg

- Pulse rate < 40 or > 85 beats per minute (bpm)

12. Any clinically significant abnormalities in rhythm, conduction or morphology of the
resting ECG and any clinically significant abnormalities in the 12-lead ECG, as
considered by the investigator that may interfere with the interpretation of QTc
interval changes, including abnormal ST-T-wave morphology, particularly in the
protocol defined primary lead or left ventricular hypertrophy.

13. Prolonged QT interval corrected for heart rate (HR) using Fridericia's formula (QTcF)
> 450 ms or family history of long QT syndrome.

14. PR(PQ) interval shortening < 120 ms (PR > 110 ms but < 120 ms is acceptable if there
is no evidence of ventricular pre-excitation).

15. PR (PQ) interval prolongation (> 240 ms) intermittent second (Wenckebach block while
asleep is not exclusive) or third degree AV block, or AV dissociation.

16. Persistent or intermittent complete bundle branch block (BBB), incomplete bundle
branch block (IBBB), or intraventricular conduction delay (IVCD) with QRS > 110 ms.
Subjects with QRS > 110 ms but < 115 ms are acceptable if there is no evidence of, for
example, ventricular hypertrophy or pre-excitation.

17. Known or suspected history of drug abuse, as judged by the investigator.

18. Current smokers or those who have smoked or used nicotine products within the previous
3 months.

19. History of alcohol abuse or excessive intake of alcohol, as judged by the
investigator.

20. Positive screen for drugs of abuse or cotinine (nicotine) at screening or admission to
the unit.

21. History of severe allergy/hypersensitivity or ongoing clinically significant
allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity
to drugs with a similar chemical structure or class to ADZ7594.

22. Excessive intake of caffeine containing drinks or food (e.g., coffee, tea, chocolate),
as judged by the investigator.

23. Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks
prior to the first administration of investigational drug.

24. Use of any prescribed or non-prescribed medication including antacids, analgesics
(other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of
20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to
the first administration of investigational drug or longer if the medication has a
long half-life.

25. Has received another new chemical entity (defined as a compound which has not been
approved for marketing in the US) within 30 days or at least 5 half-lives (whichever
is longer) of the first administration of investigational drug in this study. The
period of exclusion begins 3 months after the final dose or 1 month after the last
visit whichever is the longest.

Note: Subjects consented and screened, but not randomized in this study or a previous
phase I study, are not excluded.

26. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship,
trusteeship, or committed to an institution by governmental or juridical order.

27. Subjects who have previously received AZD7594.

28. Involvement of any Astra Zeneca or study site employee or their close relatives.

29. Judgment by the investigator that the subject should not participate in the study if
they have any ongoing or recent (i.e., during the screening period) minor medical
complaints that may interfere with the interpretation of study data or are considered
unlikely to comply with study procedures, restrictions and requirements.

30. Subjects who are vegans or have medical dietary restrictions.

31. Subjects who cannot communicate reliably with the investigator. It is acceptable to
make use of an interpreter. The informed consent document (ICD) must be available in
the Japanese language.

In addition, any of the following is regarded as a criterion for exclusion from the
genetic research:

32. Previous bone marrow transplant.

33. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the
genetic sample collection