A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD7594 Inhaled Formulation in Healthy Japanese Men
Condition: Asthma; Chronic Obstructive Pulmonary Disease COPD
MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: AZD7594 inhalation powder (200 μg); AZD7594 inhalation powder (400 μg); AZD7594 pressurized inhalation suspension (200 μg); AZD7594 placebo inhalation powder; AZD7594 placebo pressurized inhalation suspension
Intervention description: 200 μg AZD7594 inhalation powder via multi-dose dry powder inhaler (DPI); Cohort 2: 400 μg AZD7594 inhalation powder via multi-dose DPI Cohort 3: 1600 μg (4 x 400 μg inhalations) AZD7594 inhalation powder via multi-dose DPI; 400 μg (2 x 200 μg inhalations) AZD7594 pressurized inhalation suspension via pressurized metered dose inhaler (pMDI); AZD7594 placebo inhalation powder via multi-dose DPI; AZD7594 placebo pressurized inhalation suspension via pressurized metered dose inhaler (pMDI)
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Enrollment: 27.0
Sex: Male
Minimum age: 20 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Safety; Pharmacokinetics; Pharmacodynamics; Glucocorticoid receptor modulator; Healthy male subjects

Summary:

      This is a randomized, single-blind, placebo-controlled, sequential-group study to assess the
      safety and tolerability as well as how the drug (AZD7594) affects the body (pharmacodynamics
      [PD]) and how the body affects the drug (pharmacokinetics [PK]) when AZD7594 is given as
      single and multiple ascending doses once daily by inhalation to healthy male Japanese
      subjects, compared with placebo (non-active drug)
    

Eligibility criteria:

        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