A Study to Evaluate the Amount of Drug That Becomes Available to the Blood Circulation When Inhaled by a Nebulizer and Dry Powder Inhaler in Healthy Subjects.

NCT04072562 | Completed Phase 1

• 1 other identifier: D3742C00001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the relative bioavailability of the AZD7594 nebulized formulations (test) and the dry powder formulation (reference). The study results will provide information on the pharmacokinetic (PK) profile following use of the 2 devices to be used in further clinical development.

Conditions

Asthma

Keywords

Bioavailability; Pharmacokinetics; Safety; Selective glucocorticoid receptor modulator

Outcome Measures

Primary Outcomes (6)

• Maximum observed plasma concentration (Cmax)

  To estimate the relative bioavailability of AZD7594 following inhalation via nebulizer Omron NE C900-E (2 dose levels) and via DPI SD3FL

  At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)

• Area under plasma concentration-time curve from zero to infinity (AUC)

  To estimate the relative bioavailability of AZD7594 following inhalation via nebulizer Omron NE C900-E (2 dose levels) and via DPI SD3FL

  At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)

• Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC0-t)

  To estimate the relative bioavailability of AZD7594 following inhalation via nebulizer Omron NE C900-E (2 dose levels) and via DPI SD3FL

  At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)

• Individual ratios of test versus reference for AUC

  To estimate the relative bioavailability of AZD7594 following inhalation via nebulizer Omron NE C900-E (2 dose levels) and via DPI SD3FL

  At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)

• Individual ratios of test versus reference for AUC0-t

  To estimate the relative bioavailability of AZD7594 following inhalation via nebulizer Omron NE C900-E (2 dose levels) and via DPI SD3FL

  At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)

• Individual ratios of test versus reference for Cmax

  To estimate the relative bioavailability of AZD7594 following inhalation via nebulizer Omron NE C900-E (2 dose levels) and via DPI SD3FL

  At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)

Secondary Outcomes (46)

• Time to reach maximum observed plasma concentration (tmax)

  At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)

• Terminal elimination rate constant (λz)

  At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)

• Half-life associated with terminal slope (λz) of a semilogarithmic concentration-time curve (t1/2λz)

  At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)

• Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT)

  At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)

• Apparent total body clearance of drug from plasma after extravascular administration (CL/F)

  At pre-dose, at 15, 30, and 45 minutes, and at 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours post dose (Days 1, 2, 3, 4 and 5)

Other Outcomes (1)

• AZD7594 concentrations in dried blood PK sample

  Days 1, 2 and 3 (2, 6, 12, 24 and 48 h post dose)

Study Arms (3)

AZD7594 0.7 mg

EXPERIMENTAL

The study subjects will receive AZD7594 via nebulizer, during 8 minutes: 0.7 mg, delivered dose 1 inhalation

Drug: AZD7594

AZD7594 1.6 mg

EXPERIMENTAL

The study subjects will receive AZD7594 via nebulizer, during 8 minutes: 1.6 mg, delivered dose 1 inhalation

Drug: AZD7594

AZD7594 720 μg

ACTIVE COMPARATOR

The study subjects will receive AZD7594 via DPI: 0.72 mg, delivered dose (792 µg nominal dose) 1 inhalation

Drug: AZD7594

Interventions

AZD7594 DRUG

Treatment A: The study drug is a nebulizer suspension with strength 2.8 mg/mL using 2 mL in the device. The study drug is administered via oral inhalation. Treatment B: The study drug is a nebulizer suspension with strength 6.3 mg/mL using 2 mL in the device. The study drug was administered via oral inhalation. Treatment C: The study drug is an inhalation powder. The study drug was administered via oral inhalation.

AZD7594 0.7 mg; AZD7594 1.6 mg; AZD7594 720 μg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study specific procedures.
• Healthy male and female subjects aged 18 - 55 years (inclusive) at Screening with suitable veins for cannulation or repeated venepuncture.
• Females must have a negative pregnancy test at screening and on admission to the unit for each treatment period, and must not be lactating. Women of child-bearing potential (WOCBP) must be stable on their chosen method of highly effective birth control for a minimum of 3 months prior to Visit 1, and willing to use that for the entire duration of the study (from the time they sign the informed consent), and for 14 days after the last dose of IMP. They must agree not to become pregnant or donate ova throughout the study and for 14 days after the last dose of IMP. Male subjects must be surgically sterile or be willing to use a condom during the study.
• Have a body mass index (BMI) between 18 and 29.9 kg/m2 (inclusive) and weigh at least 50 kg and no more than 100 kg (inclusive).
• Subject is able to understand and communicate in German.

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the PI, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
• History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• History of Gilbert's syndrome, history of cholecystectomy or gall stone.
• History of tuberculosis, any other significant lung diseases like surgeries, asthma, chronic obstructive pulmonary disease.
• Upper respiratory tract infections (excluding otitis media) within 14 days of the first study day, or lower respiratory tract infection within 3 months prior to Screening.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
• Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, at screening and first admission to the study unit (first treatment period) as judged by the PI.
• Any clinically significant abnormal findings in vital signs at screening and first admission to the study unit (first treatment period), as judged by the PI, and defined as:
• Systolic BP \<90 mmHg or ≥140 mmHg and diastolic BP \<50 mmHg or ≥90 mmHg
• Heart rate \<50 bpm or \>90 bpm
• Any clinically significant abnormalities on 12-lead ECG at screening and first admission to the study unit (first treatment period), as judged by the PI, and defined as:
• Sick sinus syndrome
• Arrhythmia
• Prolonged QT interval corrected using Fridericia's formula \> 450 ms
• Any positive result at screening for serum hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) results.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Berlin, 14050, Germany

Location

MeSH Terms

Conditions

Asthma

Interventions

velsecorat

Condition Hierarchy (Ancestors)

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

Study Officials

• Rainard Fuhr

  Parexel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2019
• First Posted: August 28, 2019
• Study Start: September 19, 2019
• Primary Completion: November 28, 2019
• Study Completion: November 28, 2019
• Last Updated: December 16, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)