A Study to Assess the Effect of Particle Size of AZD7594 on Pharmacokinetics (PK) After a Single Inhaled Dose When Administered Using the Dry Powder Inhaler in Healthy Volunteers

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02928354
• Date of registration: 07/10/2016
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: A Study to Assess the Effect of Particle Size of AZD7594 on Pharmacokinetics (PK) After a Single Inhaled Dose When Administered Using the Dry Powder Inhaler in Healthy Volunteers
• Scientific title: A Randomized Open Label Three-Way Crossover Study in Healthy Male Volunteers to Investigate the Effect of Particle Size on Pharmacokinetics Following a Single Inhaled Dose of AZD7594 Via a Dry Powder Inhaler
• Date of first enrolment: November 25, 2016
• Target sample size: 12
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02928354
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Germany

Contacts

• Name: Dr. Thomas Körnicke
• Affiliation: PAREXEL Early Phase Clinical Unit Berlin

Key inclusion & exclusion criteria

Inclusion Criteria:

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

2. Healthy male subjects aged 18 to 55 years (inclusive) with suitable veins for
cannulation or repeated venipuncture.

3. Have a body mass index (BMI) between 18 and 29.9 kg/m2 inclusive and weigh at least 50
kg and no more than 100 kg inclusive.

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 IMP.

5. Be able to inhale from the DPI devices according to given instructions.

6. Subjects must read, speak and understand German language.

Exclusion Criteria:

1. History of any clinically significant disease or disorder which, in the opinion of the
PI, 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, 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 IMP.

4. Any clinically significant abnormalities in clinical chemistry, hematology or
urinalysis results, at screening and first admission to the study unit as judged by
the PI.

5. Any clinically significant abnormal findings in vital signs at screening and first
admission to the study unit, as judged by the PI. Abnormal vital signs, after 10
minutes supine rest, defined as any of the following: - Systolic BP (SBP) < 90 mmHg or
> 140 mmHg - Diastolic BP (DBP) < 50 mmHg or > 90 mmHg - Heart rate < 45 or > 90 beats
per minute.

6. Any clinically significant abnormalities on 12-lead ECG at screening and first
admission to the study unit, as judged by the PI.

7. Any positive result on screening for serum hepatitis surface antigen or antiHBc
antibody suggestive of hepatitis B infection, hepatitis C antibody, and human
immunodeficiency virus (HIV) antibody.

8. Known or suspected history of drug abuse, as judged by the PI.

9. Has received another new chemical entity (defined as a compound which has not been
approved for marketing) within 3 months of the first administration of IMP in this
study. The period of exclusion begins 3 months after the final dose or one 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.

10. Plasma donation within 1 month of screening or any blood donation/loss more than 500
mL during the 3 months prior to screening.

11. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as
judged by the PI or history of hypersensitivity to drugs with a similar chemical
structure or class to AZD7594.

12. Current smokers or those who have smoked or used nicotine products within the 3 months
prior to screening.

13. Subjects who are not able to perform correct spirometry tests at screening.

14. Subjects with forced expiratory volume at one second (FEV1) and forced vital capacity
(FVC) <80% predicted (calculated) values and FEV1/FVC ratio <0.7 in pulmonary function
test (spirometry) at Screening Visit.

15. Positive screen for drugs of abuse or cotinine at screening or on each admission to
the study center or positive screen for alcohol on each admission to the study center.

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 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 IMP or longer if the medication has a long half-life.

18. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as
judged by the PI.

19. Involvement of any AstraZeneca, PAREXEL or study site employee or their close
relatives.

20. Subjects who have previously received AZD7594.

21. Judgment by the PI that the volunteer 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.

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



Age minimum: 18 Years
Age maximum: 55 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Asthma, Chronic Obstructive Pulmonary Disease (COPD)

Intervention(s)

Drug: Treatment A - AZD7594

Drug: Treatment B - AZD7594

Drug: Treatment C - AZD7594

Primary Outcome(s)

Maximum observed plasma concentration (Cmax) [Time Frame: Pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose]

Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC last) [Time Frame: Pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose]

Area under plasma concentration-time curve from time zero to infinity (AUC) [Time Frame: Pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose]

Secondary Outcome(s)

Apparent total body clearance of drug from plasma after extravascular administration, estimated as dose divided by AUC (CL/F) [Time Frame: pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose]

Electrocardiogram (ECG) [Time Frame: Safety ECG will be performed prior to IMP administration and 1, 4 and 24 hours post-IMP administration on Day 1 of each Treatment Period]

Mean residence time from zero to infinity (MRT) [Time Frame: pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose]

Time to reach maximum observed plasma concentration (tmax) [Time Frame: Pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose]

Apparent volume of distribution during the terminal phase after extravascular administration estimated by dividing CL/F by ?z (Vz/F) [Time Frame: pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose]

Adverse events (AEs) [Time Frame: Throughout the study ie. from screening (Day -28) upto follow up visit i.e.. 10 days after last IMP administration]

Clinical laboratory assessments (hematology, clinical chemistry (including serum potassium and glucose) [Time Frame: Safety laboratory tests will be performed at screening, Day 1, Day 11, 240 h post dose and follow up visit]

Vital signs (systolic and diastolic blood pressure [BP], pulse rate) [Time Frame: Vital signs: pulse, blood pressure and oral body temperature will be measured, pre-dose and 1, 4, 24 hours post dose of each Treatment Period]

Spirometry [Time Frame: On Day 1 of each Treatment Period spirometry will be performed pre-dose and at 0.5 and 1 hours post dose]

Terminal elimination rate constant, estimated by log-linear least squares regression of the terminal part of the concentration-time curve (?z) [Time Frame: Pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose]

Physical examination [Time Frame: On screening (Day -28), Day 1 to 3 and follow up visit i.e., 10 days after last IMP administration]

Half-life associated with terminal slope (?z) of a semi-logarithmic concentration-time curve (t ½,?z) [Time Frame: Pre-dose and at 15, 30, and 45 minutes, and 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48, 72, 96, 144 and 240 hours post dose]

Secondary ID(s)

D3741C00006

Source(s) of Monetary Support

Please refer to primary and secondary sponsors