A Study to Assess the Bioavailability and to Compare the Pharmacokinetics of AZD7594 Inhaled Via Monodose Inhaler and Multiple-dose Dry Powder Inhalers (DPI) or Pressurized Metered-dose Inhaler (pMDI) in Healthy Male Subjects
Condition: Asthma; Chronic Obstructive Pulmonary Disease (COPD)
MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: AZD7594 Solution for infusion (150 μg intravenous formulation); AZD7594 Oral suspension (1200 μg oral formulation); AZD7594 Inhalation powder (400 μg) by DPI Device 1 (monodose inhaler); AZD7594 Inhalation powder (400 μg) by DPI device 2 (multiple-dose inhaler); AZD7594 Pressurized inhalation suspension (400 μg) by pMDI
Intervention description: Solution for infusion 0.01 mg/ml; AZD7594 150 μg IV; 0.1 - 10 mg/g oral solution; AZD7594 1200 μg oral; Inhalation powder, hard capsules 400 μg Monodose inhaler; AZD7594 400 μg by dry powder inhaler (DPI) Device 1 (Monodose inhaler); Inhalation powder, multiple-dose dry powder inhaler (DPI) 400 μg; AZD7594 400 μg by DPI Device 2 (multiple-dose DPI); Inhalation suspension 200 μg; AZD7594 400 μg by pressurized metered-dose inhaler (pMDI); 2 puffs x 200 μg = 400 μg
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: Male
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: AZD7594; Bioavailability; Healthy male subjects; Safety; Tolerability; Pharmacokinetics; Monodose inhaler; Multiple-dose dry powder inhaler

Summary:

      This is an open-label,partially randomized, four-period study in healthy male subjects to
      assess the bioavailability and pharmacokinetics of a single dose of AZD7594 when administered
      intravenously, orally and inhaled via two different dry powder inhalers (DPIs) and a
      pressurized meter-dose inhaler (pMDI)
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provision of signed and dated, written informed consent prior to any study specific
             procedures.

          2. Healthy male subjects aged 18 - 45 years with suitable veins for cannulation or
             repeated venipuncture.

          3. Have a body mass index (BMI) between 18 and 30 kg/m2, inclusive, and weigh at least 50
             kg.

          4. Subjects should be willing to follow reproductive restrictions to prevent pregnancy
             and drug exposure of a female partner and refrain from donating sperm or fathering a
             child from the first day of dosing until 3 months after the last dose of
             investigational product.

          5. Be able to inhale from the dry powder inhaler (DPI) devices and the pressurized
             metered-dose inhaler (pMDI) device according to given instructions.

        Exclusion Criteria:

          1. History of any clinically significant disease or disorder which, in the opinion of the
             Investigator, may either put the volunteer at risk because of participation in the
             study, or influence the results or the volunteer'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, major medical/surgical procedure, or trauma within
             4 weeks of the first administration of Investigational medicinal product (IMP).

          4. Any clinically significant abnormalities in clinical chemistry, hematology, or
             urinalysis results at screening and check-in, as judged by the investigator.

          5. Any clinically significant abnormal findings in vital signs after a 5 minute rest at
             screening and check-in, as judged by the investigator, defined as any of the
             following:

               -  Systolic blood pressure (BP) > 140 mm Hg;

               -  Systolic BP < 90 mm Hg;

               -  Diastolic BP > 90 mm Hg;

               -  Diastolic BP < 60 mm Hg; or

               -  Heart rate < 40 or > 85 beats per minute (bpm).

          6. Any clinically significant abnormities in physical examination or lung function, as
             judged by the investigator.

          7. Any clinically significant abnormalities on 12-lead electrocardiogram (ECG) at
             screening and check-in, as judged by the investigator.

          8. Any clinically important abnormalities in rhythm, conduction or morphology of resting
             ECG that may interfere with the interpretation of QTc (QT interval corrected) interval
             changes. This includes subjects with any of the following:

               -  Clinically significant PR (PQ) (ECG interval measured from the onset of the P
                  wave to the onset of the QRS complex) interval prolongation;

               -  Intermittent or persistent second or third degree AV block;

               -  Persistent or intermittent complete bundle branch block (BBB), incomplete bundle
                  branch block (IBBB), or intraventricular conduction delay (IVCD) with QRS (ECG
                  interval measured from the onset of the QRS complex to the J point) > 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; or

               -  Abnormal T wave morphology, particularly in the protocol defined primary lead.

          9. Prolonged QTcF (QT interval corrected for heart rate using Fridericia's formula) > 450
             msec or family history of long QT (ECG interval measured from the onset of the QRS
             complex to the end of the T wave) syndrome.

         10. Known or suspected history of drug abuse, as judged by the investigator

         11. Current smokers or those who have smoked or used nicotine products within the previous
             3 months.

         12. History of alcohol abuse or excessive intake of alcohol as judged by the investigator.

         13. Positive screen for drugs of abuse, alcohol, and cotinine at screening or on each
             admission to the study center.

         14. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as
             judged by the investigator or history of hypersensitivity to drugs with a similar
             chemical structure or class to AZD7594 or to excipients.

         15. Excessive intake of caffeine containing drinks e.g., coffee, tea, caffeine containing
             energy drinks and cola (in total no more than 3 cups per day).

         16. Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks
             prior to the first administration of IMP.

         17. Use of any prescribed or non-prescribed medication including vaccines, antacids,
             analgesics (other than paracetamol/acetaminophen), herbal remedies, vitamins and
             minerals during the 2 weeks prior to the first administration of IMP or longer if the
             medication has a long half-life. Occasional use of paracetamol/acetaminophen is
             allowed for minor pains and headaches (no more than 3000 mg/day).

         18. Plasma donation within 1 month of screening or any blood donation/loss more than 500
             mL during the 3 months prior to screening.

         19. Has participated in a clinical study investigating clinical evaluation methods 1 month
             (or at least 5 half-lives) prior to the administration of investigational product.

         20. Known Gilbert's syndrome, family history of Gilbert's syndrome or suspicion of
             Gilbert's syndrome based on liver function tests.

         21. Any contraindication against the use of vagolytic or sympaticomimetic drugs, as judged
             by the investigator.

         22. Involvement of any AstraZeneca, PAREXEL or study site employee or their close
             relatives.

         23. Any positive result on screening for serum hepatitis B surface antigen (HBsAg),
             hepatitis C antibody and human immunodeficiency virus (HIV) antibody.

         24. 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.

         25. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship,
             trusteeship, or committed to an institution by governmental or juridical order.