Study to Evaluate the Pharmacokinetics and Pharmacodynamics of AZD4604 Given Via the Turbuhaler® Device in Adults With Mild Asthma.

A Phase Ib, Multicentre, Randomised, Single-blind, Parallel-group, Placebo-controlled, Study to Characterise the Pharmacokinetics and Pharmacodynamics of AZD4604 Administered Via the Turbuhaler® Device in Adults With Mild Asthma

The study will investigate the Pharmacokinetic (PK), Pharmacodynamic (PD), the safety and tolerability of AZD4604, as well as to examine the effect of Fractional exhaled Nitric Oxide (FeNO) following the administration of the multiple doses of AZD4604 via Turbuhaler device.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: AZD4604; Device: Genuair; Device: Turbuhaler; Other: Placebo

Detailed Description

This is a multicentre, randomised, placebo-controlled, single-blind study to characterise PK and PD of AZD4604, administered twice daily (BID) using a Turbuhaler or a Genuair device.

Participants who have mild asthma with a raised FeNO will be randomised into the study to evaluate AZD4604 versus placebo, at 2 dose levels delivered via: a) the Turbuhaler device and b) the Genuair device.

The study will be comprised of:

• A screening period (Day -42 to Day-3)
• Participants will be randomised to one of 5 treatment arms where participants will either receive BID doses of AZD4604 or placebo from Day 1 to Day 9 and a single dose on Day 10.
• A follow-up Visit on Day 16

The total duration of the study will be for 58 days.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10119
    • Research Site
  • Berlin, Germany, 10787
    • Research Site
  • Frankfurt, Germany, 60596
    • Research Site
  • Großhansdorf, Germany, 22927
    • Research Site
  • Lübeck, Germany, 23552
    • Research Site
• United Kingdom
  • Cambridge, United Kingdom, CB2 0AY
    • Research Site
  • Harrow, United Kingdom, HA1 3UJ
    • Research Site
  • Liverpool, United Kingdom, L7 8XP
    • Research Site
  • London, United Kingdom, N12 8BU
    • Research Site
  • Wythenshawe, United Kingdom, M23 9QZ
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria:

• Participant must be 18 to 65 years of age inclusive with suitable veins for cannulation or repeated venepuncture.
• Participants must have Physician-diagnosed mild asthma for at least 6 months prior to Screening Visit.
• ≥ 70% predicted for FEV1 at the Screening Visit AND on Day -1.
• Have a FeNO of ≥ 40 ppb at the Screening Visit and on Day -2.
• Body weight at least 50 kg and BMI within the range 18 to 35 kg/m2 (inclusive).
• Female participants must have a negative pregnancy test at the Screening Visit and on admission to the clinical site or prior to randomisation and must not be lactating. However, there are no restrictions on male participants or their female partners.
• Contraceptive use by females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Capable of giving signed and dated informed consent prior to any study-specific procedure.

Main Exclusion Criteria:

• History of any clinically important disease or disorder which, in the opinion of the Principal Investigator (PI), may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
• 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 and disease history suggesting abnormal immune function.
• Participants with increased risk of infection.
• Have received any vaccine in the 30 days prior to the first dose.
• History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of the study intervention.
• History of serious or severe adverse reaction or known hypersensitivity to AZD4604 or any of its additive constituents
• High sensitivity C-reactive protein > Upper Limit of Normal (ULN) at Screening Visit and Baseline/Run-in Period.
• Any clinically important abnormalities in clinical chemistry, haematology or urinalysis results as judged by the PI. The PI may consider appropriate ethnicity adjusted local reference ranges for haematology or clinical chemistry measurements, when available.
• Known or suspected history of drug abuse as judged by the PI and current smokers.
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the PI or history of hypersensitivity to drugs with a similar chemical structure or class to AZD4604.
• Use of drugs with enzyme-inducing properties such as St John's wort within 3 weeks prior to the first administration of study intervention.
• History of alcohol abuse or excessive intake of alcohol as judged by the PI.
• 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.
• Participants who cannot communicate reliably with the PI or vulnerable participants.
• 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 investigator that may interfere with the interpretation of QTc interval changes.
• Female participants who are planning a pregnancy during the study period or within one month after the last dose of study intervention.
• Exacerbation of asthma symptoms within 6 months prior to Screening Visit and Day -1 requiring the use of oral, IM or IV steroids, antibiotics, accident and emergency visit, or hospital admission.
• If in the judgement of the PI, the participant has any ongoing or recent (ie, 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, the participant should not be enrolled.
• 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 study intervention in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD4604 dose A via Genuair; Participants will receive dose A of AZD4604 via Genuair device twice daily	Drug: AZD4604; Participants will receive AZD4604 via Genuair/Turbuhaler device.; Device: Genuair; Participants will either receive AZD4604 or placebo via Genuair device.
Experimental: AZD4604 dose A via Turbuhaler; Participants will receive dose A of AZD4604 via Turbuhaler device twice daily	Drug: AZD4604; Participants will receive AZD4604 via Genuair/Turbuhaler device.; Device: Turbuhaler; Participants will receive either AZD4604 or placebo via Turbuhaler device.
Experimental: AZD4604 dose B via Turbuhaler; Participants will receive dose B of AZD4604 via Turbuhaler device twice daily	Drug: AZD4604; Participants will receive AZD4604 via Genuair/Turbuhaler device.; Device: Turbuhaler; Participants will receive either AZD4604 or placebo via Turbuhaler device.
Placebo Comparator: Placebo via Genuair; Participants will receive placebo via Genuair device twice daily	Device: Genuair; Participants will either receive AZD4604 or placebo via Genuair device.; Other: Placebo; Participants will receive placebo via Genuair/Turbuhaler device.
Placebo Comparator: Placebo via Turbuhaler; Participants will receive placebo via Turbuhaler device twice daily	Device: Turbuhaler; Participants will receive either AZD4604 or placebo via Turbuhaler device.; Other: Placebo; Participants will receive placebo via Genuair/Turbuhaler device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed drug concentration (Cmax) of AZD4604	The Cmax of AZD4604 at Day 10 of dosing with dose A and dose B when delivered by the Turbuhaler device will be characterised.	Day 9 (Pre-dose) and Day 10 (Pre-dose and Post-dose)
Time to reach maximum observed concentration (tmax) of AZD4604	The tmax of AZD4604 at Day 10 of dosing with dose A and dose B when delivered by the Turbuhaler device will be characterised.	Day 9 (Pre-dose) and Day 10 (Pre-dose and Post-dose)
Area under concentration-time curve in the dosing interval (AUCtau) of AZD4604	The AUCtau of AZD4604 at Day 10 of dosing with dose A and dose B when delivered by the Turbuhaler device will be characterised.	Day 9 (Pre-dose) and Day 10 (Pre-dose and Post-dose)
Apparent total body clearance (CL/F) of AZD4604	The CL/F of AZD4604 at Day 10 of dosing with dose A and dose B when delivered by the Turbuhaler device will be characterised.	Day 10 (Pre-dose and Post-dose)
Apparent volume of distribution based on the terminal phase (VZ/F) of AZD4604	The VZ/F of AZD4604 at Day 10 of dosing with dose A and dose B when delivered by the Turbuhaler device will be characterised.	Day 10 (Pre-dose and Post-dose)
Dose normalised AUCtau (AUCtau/D) of AZD4604	The AUCtau/D of AZD4604 at Day 10 of dosing with dose A and dose B when delivered by the Turbuhaler device will be characterised.	Day 9 (Pre-dose) and Day 10 (Pre-dose and Post-dose)
Dose normalised Cmax (Cmax/D) of AZD4604	The Cmax/D of AZD4604 at Day 10 of dosing with dose A and dose B when delivered by the Turbuhaler device will be characterised.	Day 9 (Pre-dose) and Day 10 (Pre-dose and Post-dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline to end of treatment in FeNO levels	The change in FeNO levels from baseline to end of treatment after administration of AZD4604 delivered via Turbuhaler device will be evaluated.	From Screening visit (Day -42 to Day -3), Day -2 to Day 4, Day 9 to Day 10, Follow-up visit (Day 16)
Percentage of participants who achieve a FeNO < 25 ppb Cmax/D	The percentage of participants who achieve a FeNO <25 ppb after administration of AZD4604 delivered via Turbuhaler device will be evaluated.	From Screening visit (Day -42 to Day -3), Day -2 to Day 4, Day 9 to Day 10, Follow-up visit (Day 16)
Change from baseline to end of treatment in FeNO levels	The change in FeNO levels from baseline to end of treatment after administration of AZD4604 delivered via Turbuhaler and Genuair devices will be evaluated.	From Screening visit (Day -42 to Day -3), Day -2 to Day 4, Day 9 to Day 10, Follow-up visit (Day 16)
Maximum observed drug concentration (Cmax) of AZD4604	The Cmax of AZD4604 at Day 10 of dosing with dose A, when delivered by the Genuair device will be characterised.	Day 9 and Day 10
Time to reach maximum observed concentration (tmax) of AZD4604	The tmax of AZD4604 at Day 10 of dosing with dose A, when delivered by the Genuair device will be characterised.	Day 9 and Day 10
Area under concentration-time curve in the dosing interval (AUCtau) of AZD4604	The AUCtau of AZD4604 at Day 10 of dosing with dose A, when delivered by the Genuair device will be characterised.	Day 9 and Day 10
Apparent total body clearance (CL/F) of AZD4604	The CL/F of AZD4604 at Day 10 of dosing with dose A, when delivered by the Genuair device will be characterised.	Day 10
Apparent volume of distribution based on the terminal phase (VZ/F)	The VZ/F of AZD4604 at Day 10 of dosing with dose A, when delivered by the Genuair device will be characterised.	Day 10
Dose normalised AUCtau (AUCtau/D) of AZD4604	The AUCtau/D of AZD4604 at Day 10 of dosing with dose A, when delivered by the Genuair device will be characterised.	Day 9 and Day 10
Dose normalised Cmax (Cmax/D) of AZD4604	The Cmax/D of AZD4604 at Day 10 of dosing with dose A, when delivered by the Genuair device will be characterised.	Day 9 and Day 10
Maximum observed drug concentration (Cmax) of AZD4604	The Cmax of AZD4604 at Day 10 of dosing with dose A is compared via the Turbuhaler and Genuair devices.	Day 9 and Day 10
Area under concentration-time curve in the dosing interval (AUCtau)	The AUCtau of AZD4604 at Day 10 of dosing with dose A is compared via the Turbuhaler and Genuair devices.	Day 9 and Day 10

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2025
• Primary Completion (Actual): May 29, 2025
• Study Completion (Actual): May 29, 2025

Study Registration Dates

• First Submitted: December 10, 2024
• First Submitted That Met QC Criteria: December 10, 2024
• First Posted (Actual): December 13, 2024

Study Record Updates

• Last Update Posted (Estimated): June 5, 2025
• Last Update Submitted That Met QC Criteria: June 4, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Turbuhaler device; Genuair device; Janus Kinase 1 inhibitor
• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Asthma
• Other Study ID Numbers: D8210C00006; 2024-516474-30-00 (Other Identifier: EU CT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure."Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environmentVivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes