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

NCT ID: NCT02645253

Last Updated: 2018-02-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-12
• Study Completion Date: 2016-04-17

Brief 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)

Detailed Description

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

Conditions

Asthma; Chronic Obstructive Pulmonary Disease COPD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Cohort 1

AZD7594 inhalation powder (200 μg) or AZD7594 placebo inhalation powder via multi-dose dry powder inhaler (DPI)

Group Type: EXPERIMENTAL

AZD7594 inhalation powder (200 μg)

Intervention Type: DRUG

200 μg AZD7594 inhalation powder via multi-dose dry powder inhaler (DPI)

AZD7594 placebo inhalation powder

Intervention Type: DRUG

AZD7594 placebo inhalation powder via multi-dose DPI

Cohort 2

AZD7594 inhalation powder (400 μg) or AZD7594 placebo inhalation powder via multi-dose dry powder inhaler (DPI)

Group Type: EXPERIMENTAL

AZD7594 inhalation powder (400 μg)

Intervention Type: DRUG

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

AZD7594 placebo inhalation powder

Intervention Type: DRUG

AZD7594 placebo inhalation powder via multi-dose DPI

Cohort 3

1600 μg AZD7594 inhalation powder (4 x 400 μg) or AZD7594 placebo inhalation powder via multi-dose dry powder inhaler (DPI)

Group Type: EXPERIMENTAL

AZD7594 inhalation powder (400 μg)

Intervention Type: DRUG

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

AZD7594 placebo inhalation powder

Intervention Type: DRUG

AZD7594 placebo inhalation powder via multi-dose DPI

Cohort 4

400 μg AZD7594 pressurized inhalation suspension (2 x 200 μg inhalations) or placebo pressurized inhalation suspension via pressurized metered dose inhaler (pMDI)

Group Type: EXPERIMENTAL

AZD7594 pressurized inhalation suspension (200 μg)

Intervention Type: DRUG

400 μg (2 x 200 μg inhalations) AZD7594 pressurized inhalation suspension via pressurized metered dose inhaler (pMDI)

AZD7594 placebo pressurized inhalation suspension

Intervention Type: DRUG

AZD7594 placebo pressurized inhalation suspension via pressurized metered dose inhaler (pMDI)

Interventions

AZD7594 inhalation powder (200 μg)

200 μg AZD7594 inhalation powder via multi-dose dry powder inhaler (DPI)

Intervention Type: DRUG

AZD7594 inhalation powder (400 μg)

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

Intervention Type: DRUG

AZD7594 pressurized inhalation suspension (200 μg)

400 μg (2 x 200 μg inhalations) AZD7594 pressurized inhalation suspension via pressurized metered dose inhaler (pMDI)

Intervention Type: DRUG

AZD7594 placebo inhalation powder

AZD7594 placebo inhalation powder via multi-dose DPI

Intervention Type: DRUG

AZD7594 placebo pressurized inhalation suspension

AZD7594 placebo pressurized inhalation suspension via pressurized metered dose inhaler (pMDI)

Intervention Type: 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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Esther Yoon, M.D

Role: PRINCIPAL_INVESTIGATOR

California Clinical Trials Medical Group

Locations

Research Site

Glendale, California, United States

Countries

United States

Other Identifiers

D3741C00005

Identifier Type: -

Identifier Source: org_study_id