A Multiple Dosing (14 Days) Study to Assess Efficacy and Safety of Three Dose Levels of AZD7594, Given Once Daily by Inhalation, in Patients With Mild to Moderate Asthma

NCT ID: NCT02479412

Last Updated: 2018-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-25
• Study Completion Date: 2016-02-08

Brief Summary

This study will be a randomised, double-blind, multiple dose (14 days), placebo-controlled, multi-center study to assess efficacy and safety of three dose levels of AZD7594, given once daily by inhalation, in patients with mild to moderate asthma.

Detailed Description

This is a randomized, double-blind, multiple dosing (14 ± 1 days), placebo-controlled, incomplete block crossover, multi-center study to assess efficacy and safety of 3 dose levels of AZD7594, given once daily by inhalation, in patients with mild to moderate asthma.

This multi-center study will be conducted at multiple sites in Europe. It is planned that approximately 48 patients with mild to moderate asthma will be randomized into the study

Conditions

Asthma; Efficacy; Safety

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Sequence 1

Placebo once daily for 14 days in Period 1, 58 µg AZD7594 once daily for 14 days in Period 2 and 250 µg AZD7594 once daily for 14 days in Period 3

Group Type: EXPERIMENTAL

250 µg AZD7594 once daily

Intervention Type: DRUG

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

58 µg AZD7594 once daily

Intervention Type: DRUG

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Placebo once daily

Intervention Type: DRUG

Once daily dosing of Placebo to AZD7594 for 14 days; each dose of Placebo inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Salbutamol

Intervention Type: DRUG

Inhalation as needed

Sequence 2

Placebo once daily for 14 days in Period 1, 250 µg AZD7594 once daily for 14 days in Period 2 and 800 µg AZD7594 once daily for 14 days in Period 3

Group Type: EXPERIMENTAL

800 μg AZD7594 once daily

Intervention Type: DRUG

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

250 µg AZD7594 once daily

Intervention Type: DRUG

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Placebo once daily

Intervention Type: DRUG

Once daily dosing of Placebo to AZD7594 for 14 days; each dose of Placebo inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Salbutamol

Intervention Type: DRUG

Inhalation as needed

Sequence 3

Placebo once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and 58 µg AZD7594 once daily for 14 days in Period 3

Group Type: EXPERIMENTAL

800 μg AZD7594 once daily

Intervention Type: DRUG

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

58 µg AZD7594 once daily

Intervention Type: DRUG

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Placebo once daily

Intervention Type: DRUG

Once daily dosing of Placebo to AZD7594 for 14 days; each dose of Placebo inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Salbutamol

Intervention Type: DRUG

Inhalation as needed

Sequence 4

58 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 800 µg AZD7594 once daily for 14 days in Period 3

Group Type: EXPERIMENTAL

800 μg AZD7594 once daily

Intervention Type: DRUG

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

58 µg AZD7594 once daily

Intervention Type: DRUG

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Placebo once daily

Intervention Type: DRUG

Once daily dosing of Placebo to AZD7594 for 14 days; each dose of Placebo inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Salbutamol

Intervention Type: DRUG

Inhalation as needed

Sequence 6

250 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 58 µg AZD7594 once daily for 14 days in Period 3

Group Type: EXPERIMENTAL

250 µg AZD7594 once daily

Intervention Type: DRUG

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

58 µg AZD7594 once daily

Intervention Type: DRUG

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Placebo once daily

Intervention Type: DRUG

Once daily dosing of Placebo to AZD7594 for 14 days; each dose of Placebo inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Salbutamol

Intervention Type: DRUG

Inhalation as needed

Sequence 8

800 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 250 µg AZD7594 once daily for 14 days in Period 3

Group Type: EXPERIMENTAL

800 μg AZD7594 once daily

Intervention Type: DRUG

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

250 µg AZD7594 once daily

Intervention Type: DRUG

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Placebo once daily

Intervention Type: DRUG

Once daily dosing of Placebo to AZD7594 for 14 days; each dose of Placebo inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Salbutamol

Intervention Type: DRUG

Inhalation as needed

Sequence 5

58 µg AZD7594 once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3

Group Type: EXPERIMENTAL

800 μg AZD7594 once daily

Intervention Type: DRUG

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

58 µg AZD7594 once daily

Intervention Type: DRUG

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Placebo once daily

Intervention Type: DRUG

Once daily dosing of Placebo to AZD7594 for 14 days; each dose of Placebo inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Salbutamol

Intervention Type: DRUG

Inhalation as needed

Sequence 7

250 µg AZD7594 once daily for 14 days in Period 1, 58 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3

Group Type: EXPERIMENTAL

250 µg AZD7594 once daily

Intervention Type: DRUG

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

58 µg AZD7594 once daily

Intervention Type: DRUG

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Placebo once daily

Intervention Type: DRUG

Once daily dosing of Placebo to AZD7594 for 14 days; each dose of Placebo inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Salbutamol

Intervention Type: DRUG

Inhalation as needed

Sequence 9

800 µg AZD7594 once daily for 14 days in Period 1, 250 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3

Group Type: EXPERIMENTAL

800 μg AZD7594 once daily

Intervention Type: DRUG

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

250 µg AZD7594 once daily

Intervention Type: DRUG

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Placebo once daily

Intervention Type: DRUG

Once daily dosing of Placebo to AZD7594 for 14 days; each dose of Placebo inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Salbutamol

Intervention Type: DRUG

Inhalation as needed

Interventions

800 μg AZD7594 once daily

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Intervention Type: DRUG

250 µg AZD7594 once daily

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Intervention Type: DRUG

58 µg AZD7594 once daily

Once daily dosing of 800 µg AZD7594 for 14 days; each dose of AZD7594 inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Intervention Type: DRUG

Placebo once daily

Once daily dosing of Placebo to AZD7594 for 14 days; each dose of Placebo inhalation powder will be administered via a dry powder monodose inhaler as 2 hard capsules with 2 inhalations per capsule

Intervention Type: DRUG

Salbutamol

Inhalation as needed

Intervention Type: DRUG

Other Intervention Names

High dose of AZD7594; Medium dose of AZD7594; Low dose of AZD7594; Placebo; Rescue medication

Eligibility Criteria

Inclusion Criteria

• Body mass index of 18 to 35 kg/m2
• Men and women 18 to 75 years of age, inclusive
• Patients need to be non-smokers or ex-smokers (quit ≥ 6 months before the Visit 1) with total smoking history of < 10 pack years
• Documented clinical diagnosis of asthma for ≥ 6 months before the Visit 1
• Patients on low-dose inhaled corticosteroids (ICS) (equivalent of budesonide ≤ 400 μg per day) or low-dose ICS/long-acting β-2 agonist (LABA), or not on any inhaled steroids, or patients on montelukast
• Patients should be controlled on low dose budesonide during the first 14 ±2 days of Run-in Part 1, i.e., they need to have ACQ-5 of ≤ 1.5 at Visit 2.
• Prebronchodilator FEV1 at Visit 3 should be between 40% and 90% of predicted (mean of 2 predose measurements taken 30 minutes apart).
• All patients need to have FeNO concentrations of ≥ 25 parts per billion at Visit 3
• Demonstrate the ability to use the study inhalation device properly
• Women must be of nonchildbearing potential defined as meeting 1 of the following criteria:

• Permanently or surgically sterilized, including hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy
• Postmenopausal; aged ≤ 50 years and have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle stimulating hormone levels in the postmenopausal range
• Postmenopausal; aged > 50 years and have been amenorrheic for 12 months or more, following cessation of all exogenous hormonal treatments
• Male patients should be willing to use a condom to prevent pregnancy and exposure of a female partner to AZD7594 and should refrain from donating sperm or fathering a child from the first day of dosing until 3 months after the last dose of IMP.

Exclusion Criteria

• Known or suspected hypersensitivity to the IMPs or excipients, including lactose
• Systemic steroid use in the 6 weeks before Visit 1
• Any active disease other than asthma
• Patients on medium to high-dose ICS (equivalent of budesonide > 400 μg per day) or on inhaled anticholinergic combination within the 6 weeks prior to Visit 1
• Compliance with the eDiary of at least 80% of the days is expected in both Run-in and Treatment Periods. Patients with < 80% eDiary compliance during Run-in Periods would not be randomized
• Treatment with biologicals such as monoclonal antibodies or chimeric biomolecules including omalizumab within 6 months or 5 half-lives before Visit 1, whichever is longer
• History or clinical suspicion of any clinically relevant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study, or any other safety concerns in the opinion of the Investigator
• ACQ-5 ≥ 3 at any time between Visits 1 and 3
• Any contraindication against the use of vagolytic or sympathomimetic drugs as judged by the Investigator.
• Patients with hepatitis B surface antigen, hepatitis C virus antibody or human immunodeficiency virus (HIV)
• Donation of blood (≥ 450 mL) within 3 months or donation of plasma within 14 days before Visit 1
• Pregnant woman or a nursing mother
• Suspicion of Gilbert's syndrome
• Vulnerable persons (e.g., persons kept in detention)
• ACQ-5 of ≥ 3 or daily rescue use of ≥ 12 puffs for ≥ 3 consecutive days during the enrollment period
• Hypersensitivity to the active substance or to any of the excipients of the Run-in medication (i.e., budesonide)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rainard Fuhr, Dr. med.

Role: PRINCIPAL_INVESTIGATOR

PAREXEL International GmbH, Berlin, Germany

Ulrike Westerhausen, Dr.

Role: PRINCIPAL_INVESTIGATOR

Pneumologisches Studienzentrum, Berlin, Germany

Oliver Kornmann, Dr.

Role: PRINCIPAL_INVESTIGATOR

IKF Pneumologie GmbH, Frankfurt, Germany

Jutta Beier, Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Insaf GmbH, Wiesbaden, Germany

Christine Grigat, Dr.

Role: PRINCIPAL_INVESTIGATOR

Clinical Research Hamburg GmbH, Hamburg, Germany

Andrea Ludwig-Sengpiel, Dr.

Role: PRINCIPAL_INVESTIGATOR

KLB Gesundheitsforschung Lübeck GmbH, Lübeck, Germany

Dirk Skowasch, Prof.

Role: PRINCIPAL_INVESTIGATOR

University hospital of Bonn, Department of Internal Medicine II, Bonn, Germany

Anne-Marie Kirsten, Dr.

Role: PRINCIPAL_INVESTIGATOR

Pneumologisches Forschungsinstitut an der LungenClinic Großhansdorf, Großhansdorf, Germany

Tanya Kralimarkova, Dr.

Role: PRINCIPAL_INVESTIGATOR

COMAC Medical Ltd., Sofia, Bulgaria

Anneliese Linnhoff, Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Praxis für Lungen- und Bronchialheilkunde, Allergologie und Umweltmedizin

Margret Jandl, Dr.

Role: PRINCIPAL_INVESTIGATOR

Hamburger Institut für Therapie Forschung GmbH

Locations

Research Site

Sofia, , Bulgaria

Research Site

Berlin, , Germany

Research Site

Berlin, , Germany

Research Site

Berlin, , Germany

Research Site

Frankfurt, , Germany

Research Site

Großhansdorf, , Germany

Research Site

Hamburg, , Germany

Research Site

Hamburg, , Germany

Research Site

Lübeck, , Germany

Research Site

Wiesbaden, , Germany

Countries

Bulgaria; Germany

References

Brown MN, Fuhr R, Beier J, Su HL, Chen Y, Forsman H, Hamren UW, Jackson H, Aggarwal A. Efficacy and safety of AZD7594, an inhaled non-steroidal selective glucocorticoid receptor modulator, in patients with asthma: a phase 2a randomized, double blind, placebo-controlled crossover trial. Respir Res. 2019 Feb 18;20(1):37. doi: 10.1186/s12931-019-1000-7.

Reference Type: DERIVED

PMID: 30777086 (View on PubMed)

Other Identifiers

2014-005306-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D3741C00003

Identifier Type: -

Identifier Source: org_study_id