A Clinical Trial in Healthy Volunteers to Investigate a New Medicine (AZD4604) for the Treatment of Asthma

• Status: Recruiting
• Trial end date: 2022-09-26
• Target enrollment: 0
• Participant gender: All

Summary

This first in human clinical study will assess the safety and tolerability, as well as the single dose pharmacokinetics (PK), of inhaled AZD4604 in healthy volunteers (Part 1a, single ascending dose [SAD]). The single dose administration will be performed with dry powder inhaler (DPI) formulation of AZD4604. When at least 4 cohorts of the SAD part of the study have been completed, AZD4604 will be administered as a single intravenous (IV) or oral (PO) dose to 2 different cohorts of healthy volunteers (Part 1b). The main purpose is to compare the PK between IV and inhaled administration as well as between oral and inhaled administration to further characterize the PK properties of AZD4604 by the various administration routes. The results will be used to improve future study design and interpretation.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: AstraZeneca

Criteria

Inclusion Criteria:

Part 1a, 1b, and Part 2

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

2. Healthy male and female (including women of childbearing potential [WOCBP]) volunteers aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.

3. Female volunteers must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit, must not be lactating. Women of non- childbearing potential, must fulfill one of the following criteria:

1. Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle stimulating hormone levels in the postmenopausal range.

2. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not bilateral tubal ligation.

4. Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 60 kg.

5. Healthy volunteer must have a forced expiratory volume (FEV) 1 ≥ 80% of the predicted value regarding age, height, gender and ethnicity at the Screening and randomization Visits.

6. Male volunteers and their WOCBP partners should be willing to use highly effective contraception measures and should refrain from donating sperm or fathering a child from the first day of dosing until 3 months after the last dose of investigational medicinal product (IMP).

7. WOCBP must be willing to use highly effective contraception measures from the first day of dosing until at least 1 month after the last dose of IMP, such as measures that results in low failure rate, ie, less than 1% per year.

Exclusion Criteria for Part 1a, 1b, and Part 2:

1. History of any clinically important disease or disorder.

2. History of any respiratory disorders.

3. Healthy volunteer having an increased risk of infection.

4. History of cancer within the last 10 years (20 years for breast cancer) except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured. Any history of lymphoma is not allowed.

5. Disease history suggesting abnormal immune function.

6. Have received any vaccine in the 30 days prior to the first dose.

7. Has a body temperature of > 37.7°C on Day -1.

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

9. Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP.

10. Any clinically important abnormalities in clinical chemistry, hematology or urinalysis results.

11. Abnormal vital signs.

12. Known or suspected history of drug abuse.

13. Current smokers or those who have smoked or used nicotine products.

14. History of alcohol abuse or excessive intake of alcohol.

15. Positive screen for drugs of abuse or cotinine (nicotine).

16. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Principal Investigator (PI) or history of hypersensitivity to drugs with a similar chemical structure or class to AZD4604.

17. History of serious or severe adverse reaction to AZD4604 or any of its additive constituents.

18. Excessive intake of caffeine containing drinks or food (eg, coffee, tea, chocolate).

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

20. Use of any prescribed or nonprescribed medication.

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

22. 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.

23. Judgment by the PI that the volunteer should not participate in the study if they have any ongoing or recent minor medical complaints that may interfere with the interpretation of study data.

24. Healthy volunteers who are vegans or have medical dietary restrictions.

25. Vulnerable healthy volunteers.

26. Any clinically important abnormalities in rhythm, conduction or morphology of the resting electrocardiogram (ECG) and any clinically important abnormalities in the 12 lead ECG as considered by the PI that may interfere with the interpretation of QTc interval changes, including abnormal ST T wave morphology.

Part 2

27. Exacerbation of asthma symptoms within 6 months prior to Screening Visit and Day 1.

28. Use of the following medicines within the specified time before Screening Visit:

1. Long-acting β2 agonists

2. Biologics for asthma.

3. Inhaled corticosteroids.

4. Oral or injectable steroids for treatment of asthma or respiratory tract infection.

5. Intranasal steroids.

6. Leukotriene antagonists.

7. Xanthines (excluding caffeine), anticholinergics, or cromoglycate.

8. Short acting bronchodilator other than for rescue.

9. Short acting bronchodilator other than for rescue and within 12 hours of Screening Visit and Day -1 spirometry assessments.

29. Non-sterilized male patients who are sexually active with a WOCBP and WOCBP who are sexually active with a fertile male partner and who do not agree to a highly effective method of contraception.

Genetic research:

30. Previous bone marrow transplant.

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