A Study to Assess the Pharmacokinetics (PK), Pharmacodynamics (PD) and Safety of 2-Week Treatment With Inhaled AZD7594 in Adolescents (12 to 17 Years) With Asthma

NCT03976869 | Completed Phase 1 FDA Drug

• 1 other identifier: D3741C00012
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 10

Brief Summary

This is an open-label, multi-centre, Phase I study to assess the PK, PD and safety of 2 week treatment with inhaled AZD7594 in adolescent patients with asthma. The study is planned to be conducted at 4-10 study sites in the United States. The study intends to include 24 patients (12 to 17-year-old patients). For each patient, the duration of participation in the study will be approximately 5 to 7 weeks (37 to 52 days).

Conditions

Asthma

Keywords

glucocorticoid receptor (GR) modulator (SGRM); non-steroidal; Asthma; Adolescents

Outcome Measures

Primary Outcomes (7)

• Maximum observed plasma concentration at steady state (Cmax,ss) at Day 15 as part of PK evaluation

  To assess the PK profile of AZD7594 at steady state following daily inhalations for 2 weeks in adolescent patients with asthma

  Pre-dose and 15, 30 minutes, 2, 4, 6, 8, 12 hours post-dose at Day 15

• Minimum observed plasma concentration at steady state (Cmin,ss) at Day 15 as part of PK evaluation

  To assess the PK profile of AZD7594 at steady state following daily inhalations for 2 weeks in adolescent patients with asthma.

  Pre-dose and 15, 30 minutes, 2, 4, 6, 8, 12 hours post-dose at Day 15

• Observed trough plasma concentration at end of dosing interval (τ) (Ctrough) at Day 15 as part of PK evaluation

  To assess the PK profile of AZD7594 at steady state following daily inhalations for 2 weeks in adolescent patients with asthma

  Pre-dose and 15, 30 minutes, 2, 4, 6, 8, 12 hours post-dose at Day 15

• Time of maximum observed plasma concentration at steady state (tmax,ss) at Day 15 as part of PK evaluation

  To assess the PK profile of AZD7594 at steady state following daily inhalations for 2 weeks in adolescent patients with asthma.

  Pre-dose and 15, 30 minutes, 2, 4, 6, 8, 12 hours post-dose at Day 15

• Area under the plasma concentration-time curve over a dosing interval (τ) at steady state (AUCτ) at Day 15 as part of PK evaluation

  To assess the PK profile of AZD7594 at steady state following daily inhalations for 2 weeks in adolescent patients with asthma.

  Pre-dose and 15, 30 minutes, 2, 4, 6, 8, 12 hours post-dose at Day 15

• Area under the plasma concentration curve from time zero to 12 hours post-dose (AUC0-12) under plasma concentration at Day 15 as part of PK evaluation

  To assess the PK profile of AZD7594 at steady state following daily inhalations for 2 weeks in adolescent patients with asthma.

  Pre-dose and 15, 30 minutes, 2, 4, 6, 8, 12 hours post-dose at Day 15

• Apparent total body clearance after extravascular administration at steady state (CLss/F) at Day 15 as part of PK evaluation

  To assess the PK profile of AZD7594 at steady state following daily inhalations for 2 weeks in adolescent patients with asthma.

  Pre-dose and 15, 30 minutes, 2, 4, 6, 8, 12 hours post-dose at Day 15

Secondary Outcomes (3)

• Relative change from baseline in plasma cortisol area under the effect curve from time zero to 12 hours post-dose (AUEC0-12) on Day 15 as part of PD evaluation

  Pre-dose and 2, 4, 6, 8, 12 hours post-dose at Day 15

• Change from baseline in morning trough forced expiratory volume in 1 second (FEV1) on Day 15 as part of PD evaluation

  At screening, Day 1 (pre-dose and 5, 15, 60 minutes post dose), Day 15 (pre-dose) and at end of study

• Change from baseline in asthma control questionnaire (ACQ-5) on Day 15 as part of PD evaluation

  At screening, Day 1 (pre-dose) and Day 15 (pre-dose)

Other Outcomes (1)

• Number of patients with adverse events and abnormal findings in vital signs, clinical laboratory parameters, physical examination, and electrocardigram (ECG)

  From screening to follow-up (7-14 days)

Study Arms (1)

Cohort 1

EXPERIMENTAL

The study will include adolescent patients of 12 to 17 years of age, with subgroups of 12-14 years age and 15-17 years age.

Drug: AZD7594

Interventions

AZD7594 DRUG

During treatment period, AZD7594 (360 µg per day) will be administered as oral inhalation via dry powder inhaler or DPI (SD3FL inhaler).

Cohort 1

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Provision of signed and dated informed consent form (ICF) prior to any study-specific procedures from patient's parents/legal guardians is required and signed and dated informed assent from the patient.
• Patient must be 12 to 17 years of age inclusive, at the time of signing the ICF/assent.
• A minimum of 6-month documented history of asthma treated (daily or intermittently) for at least 3 months before screening (Visit 1) with either low dose inhaled corticosteroid (ICS) monotherapy or leukotriene receptor antagonist (LTRA) monotherapy.
• Pre-bronchodilator FEV1 ≥70% of the predicted normal value at screening (Visit 1).
• An ACQ-5 score \<1.5 at screening (Visit 1).
• Be non-smoker or ex-smoker who has stopped smoking (or using other nicotine products) for \>6 months prior to screening (Visit 1).
• Body mass index (BMI) above the 5th percentile for the patient's age and gender and a minimum weight of 30 kg at screening (Visit 1).
• Male or female
• Negative pregnancy test (urine or serum) for post-menarcheal female patients at screening (Visit 1).
• Post-menarcheal female patients must be willing to use a highly effective method of contraception which results in a low failure rate (ie, less than 1% per year). Sexual abstinence will be accepted as an effective method of contraception, provided a discussion occurred between the subject and investigator to confirm this lifestyle.
• Negative pregnancy test (urine or serum) for post-menarcheal female patients at baseline (Visit 4).
• FEV1 increase of at least 12% and 200 mL from baseline 15 to 30 minutes after 400 μg salbutamol (or albuterol equivalent of 360 µg) documented in the patient's medical history within 6 months of Visit 1, or confirmed at Visit 1 or Visit 2. In 12 to 14-year-old patients (who are likely to have a smaller forced vital capacity), positive reversibility testing could be based solely on the relative post bronchodilator response (at least 12%).

You may not qualify if:

• Medical conditions
• Any clinically significant disease or disorder (eg, cardiovascular, pulmonary other than asthma, gastrointestinal, liver, renal, neurological, musculoskeletal including bone fractures, endocrine including adrenal insufficiency, metabolic, malignant, psychiatric, major physical impairment, severe obesity including weight-related health problems) which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the result of the study, or the patient's ability to participate in the study.
• Any clinically relevant abnormal findings in physical examination, clinical chemistry, haematology, urinalysis, vital signs, at screening (Visit 1), which, in the opinion of the Investigator, may put the patient at risk because of his/her participation in the study.
• Prolonged QT interval corrected using Fridericia's formula (QTcF) ≥440 msec based on ECG at screening (Visit 1) or pre-dose at Visit 4, or family history of long QT syndrome.
• Prolonged PR interval (\>180 msec for ≤16-year-old patients and \>200 msec for \>16 year old patients) at screening (Visit 1) or pre-dose at Visit 4.
• Heart rate \<50 beats per minute (bpm) or \>110 bpm.
• History of or current alcohol or drug abuse (including marijuana), as judged by the Investigator.
• Patients who are positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) at screening (Visit 1).
• Hospitalisation due to asthma exacerbation or asthma exacerbation within 1 month prior to screening (Visit 1).
• Lower respiratory tract infection within 1 month prior to screening (Visit 1).
• Prior/concomitant therapy
• Patient who, in the opinion of the Investigator, is unable to abstain from protocol-defined prohibited medications during the study.
• Prior/concurrent clinical study experience
• Participation in another clinical study with an investigational drug administered in the last 3 months before Visit 1, or participation in a method development study (no drug) 1 month prior to Visit 1.
• Note: Participation is identified as the completion of a treatment related visit.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (10)

Research Site

Rolling Hills Estates, California, 90274, United States

Location

Research Site

Miami, Florida, 33165, United States

Location

Research Site

Miami Lakes, Florida, 33015, United States

Location

Research Site

Bethesda, Maryland, 20814, United States

Location

Research Site

Kansas City, Missouri, 64114, United States

Location

Research Site

Columbus, Ohio, 43207, United States

Location

Research Site

Oklahoma City, Oklahoma, 73106, United States

Location

Research Site

Boerne, Texas, 78006, United States

Location

Research Site

Dallas, Texas, 75225, United States

Location

Research Site

Murray, Utah, 84107, United States

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 Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2019
• First Posted: June 6, 2019
• Study Start: July 24, 2019
• Primary Completion: July 9, 2020
• Study Completion: July 9, 2020
• Last Updated: January 29, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (10)