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

AstraZeneca

Status and phase: Completed; Phase 2

Conditions: Asthma; Efficacy; Safety

Treatments: Drug: Salbutamol; Drug: Placebo once daily; Drug: 800 μg AZD7594 once daily; Drug: 250 µg AZD7594 once daily; Drug: 58 µg AZD7594 once daily

Study type: Interventional

Funder types: Industry

Identifiers

NCT02479412

2014-005306-37 (EudraCT Number)

D3741C00003

Details and patient eligibility

About

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.

Full 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

Enrollment: 54 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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54 participants in 9 patient groups

Sequence 1

Experimental group

Description:

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

Treatment:

Drug: 58 µg AZD7594 once daily

Drug: 250 µg AZD7594 once daily

Drug: Placebo once daily

Drug: Salbutamol

Sequence 2

Experimental group

Description:

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

Treatment:

Drug: 250 µg AZD7594 once daily

Drug: Placebo once daily

Drug: 800 μg AZD7594 once daily

Drug: Salbutamol

Sequence 3

Experimental group

Description:

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

Treatment:

Drug: 58 µg AZD7594 once daily

Drug: Placebo once daily

Drug: 800 μg AZD7594 once daily

Drug: Salbutamol

Sequence 4

Experimental group

Description:

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

Treatment:

Drug: 58 µg AZD7594 once daily

Drug: Placebo once daily

Drug: 800 μg AZD7594 once daily

Drug: Salbutamol

Sequence 6

Experimental group

Description:

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

Treatment:

Drug: 58 µg AZD7594 once daily

Drug: 250 µg AZD7594 once daily

Drug: Placebo once daily

Drug: Salbutamol

Sequence 8

Experimental group

Description:

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

Treatment:

Drug: 250 µg AZD7594 once daily

Drug: Placebo once daily

Drug: 800 μg AZD7594 once daily

Drug: Salbutamol

Sequence 5

Experimental group

Description:

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

Treatment:

Drug: 58 µg AZD7594 once daily

Drug: Placebo once daily

Drug: 800 μg AZD7594 once daily

Drug: Salbutamol

Sequence 7

Experimental group

Description:

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

Treatment:

Drug: 58 µg AZD7594 once daily

Drug: 250 µg AZD7594 once daily

Drug: Placebo once daily

Drug: Salbutamol

Sequence 9

Experimental group

Description:

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

Treatment:

Drug: 250 µg AZD7594 once daily

Drug: Placebo once daily

Drug: 800 μg AZD7594 once daily

Drug: Salbutamol