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

NCT02479412 | Completed Phase 2 Results

• 2 other identifiers: D3741C000032014-005306-37
• Study Type: interventional
• Target: 54
• Locations: 2 countries
• Sites: 10

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.

Conditions

Asthma; Efficacy; Safety

Keywords

Mild to moderate asthma; FEV1; efficacy; safety

Outcome Measures

Primary Outcomes (1)

• Efficacy of AZD7594 by Assessment of the Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 15

  Comparison of the efficacy of AZD7594 in terms of change from baseline in morning trough forced expiratory volume in 1 second (FEV1) on Day 15 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product \[IMP\] on Day 14) with placebo

  On Day 1 (pre-dose) and on Day 15 in each period

Secondary Outcomes (25)

• Efficacy of AZD7594 by Assessment of the Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) on Day 8

  On Day 1 (pre-dose) and on Day 8 in each period

• Efficacy of AZD7594 by Assessment of the Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) on Day 15

  On Day 1 (pre-dose) and on Day 15 in each period

• Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 8

  On Day 1 (pre-dose) and on Day 8 (pre-dose) in each period

• Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Vital Capacity (FVC) on Day 15

  On Day 1 (pre-dose) and on Day 15 (pre-dose) in each period

• Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Vital Capacity (FVC) on Day 8

  On Day 1 (pre-dose) and on Day 8 (pre-dose) in each period

Study Arms (9)

Sequence 1

EXPERIMENTAL

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

Drug: 250 µg AZD7594 once daily; Drug: 58 µg AZD7594 once daily; Drug: Placebo once daily; Drug: Salbutamol

Sequence 2

EXPERIMENTAL

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

Drug: 800 μg AZD7594 once daily; Drug: 250 µg AZD7594 once daily; Drug: Placebo once daily; Drug: Salbutamol

Sequence 3

EXPERIMENTAL

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

Drug: 800 μg AZD7594 once daily; Drug: 58 µg AZD7594 once daily; Drug: Placebo once daily; Drug: Salbutamol

Sequence 4

EXPERIMENTAL

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

Drug: 800 μg AZD7594 once daily; Drug: 58 µg AZD7594 once daily; Drug: Placebo once daily; Drug: Salbutamol

Sequence 6

EXPERIMENTAL

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

Drug: 250 µg AZD7594 once daily; Drug: 58 µg AZD7594 once daily; Drug: Placebo once daily; Drug: Salbutamol

Sequence 8

EXPERIMENTAL

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

Drug: 800 μg AZD7594 once daily; Drug: 250 µg AZD7594 once daily; Drug: Placebo once daily; Drug: Salbutamol

Sequence 5

EXPERIMENTAL

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

Drug: 800 μg AZD7594 once daily; Drug: 58 µg AZD7594 once daily; Drug: Placebo once daily; Drug: Salbutamol

Sequence 7

EXPERIMENTAL

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

Drug: 250 µg AZD7594 once daily; Drug: 58 µg AZD7594 once daily; Drug: Placebo once daily; Drug: Salbutamol

Sequence 9

EXPERIMENTAL

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

Drug: 800 μg AZD7594 once daily; Drug: 250 µg AZD7594 once daily; Drug: Placebo once daily; Drug: Salbutamol

Interventions

800 μg AZD7594 once daily 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

Also known as: High dose of AZD7594

Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 8; Sequence 9

250 µg AZD7594 once daily 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

Also known as: Medium dose of AZD7594

Sequence 1; Sequence 2; Sequence 6; Sequence 7; Sequence 8; Sequence 9

58 µg AZD7594 once daily 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

Also known as: Low dose of AZD7594

Sequence 1; Sequence 3; Sequence 4; Sequence 5; Sequence 6; Sequence 7

Placebo once daily 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

Also known as: Placebo

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6; Sequence 7; Sequence 8; Sequence 9

Salbutamol DRUG

Inhalation as needed

Also known as: Rescue medication

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6; Sequence 7; Sequence 8; Sequence 9

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (10)

Research Site

Sofia, 1612, Bulgaria

Location

Research Site

Berlin, 10717, Germany

Location

Research Site

Berlin, 10969, Germany

Location

Research Site

Berlin, 14050, Germany

Location

Research Site

Frankfurt, 60596, Germany

Location

Research Site

Großhansdorf, 22927, Germany

Location

Research Site

Hamburg, 20354, Germany

Location

Research Site

Hamburg, 22143, Germany

Location

Research Site

Lübeck, 23552, Germany

Location

Research Site

Wiesbaden, 65187, Germany

Location

Related Publications (1)

• 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.

  PMID: 30777086 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

velsecorat; Albuterol

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Results Point of Contact

• Title: Global Clinical Leader
• Organization: AstraZeneca AB

ClinicalTrialTransparency@astrazeneca.com

+46 31 7761000

Study Officials

• Rainard Fuhr, Dr. med.

  PAREXEL International GmbH, Berlin, Germany

  PRINCIPAL INVESTIGATOR

• Ulrike Westerhausen, Dr.

  Pneumologisches Studienzentrum, Berlin, Germany

  PRINCIPAL INVESTIGATOR

• Oliver Kornmann, Dr.

  IKF Pneumologie GmbH, Frankfurt, Germany

  PRINCIPAL INVESTIGATOR

• Jutta Beier, Dr. med.

  Insaf GmbH, Wiesbaden, Germany

  PRINCIPAL INVESTIGATOR

• Christine Grigat, Dr.

  Clinical Research Hamburg GmbH, Hamburg, Germany

  PRINCIPAL INVESTIGATOR

• Andrea Ludwig-Sengpiel, Dr.

  KLB Gesundheitsforschung Lübeck GmbH, Lübeck, Germany

  PRINCIPAL INVESTIGATOR

• Dirk Skowasch, Prof.

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

  PRINCIPAL INVESTIGATOR

• Anne-Marie Kirsten, Dr.

  Pneumologisches Forschungsinstitut an der LungenClinic Großhansdorf, Großhansdorf, Germany

  PRINCIPAL INVESTIGATOR

• Tanya Kralimarkova, Dr.

  COMAC Medical Ltd., Sofia, Bulgaria

  PRINCIPAL INVESTIGATOR

• Anneliese Linnhoff, Dr. med.

  Praxis für Lungen- und Bronchialheilkunde, Allergologie und Umweltmedizin

  PRINCIPAL INVESTIGATOR

• Margret Jandl, Dr.

  Hamburger Institut für Therapie Forschung GmbH

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2015
• First Posted: June 24, 2015
• Study Start: June 25, 2015
• Primary Completion: February 8, 2016
• Study Completion: February 8, 2016
• Last Updated: February 15, 2018
• Results First Posted: June 23, 2017

Record last verified: 2017-08

Locations

DE (9); BU (1)