Asthma
Conditions
Keywords
glucocorticoid receptor (GR) modulator (SGRM), non-steroidal, Asthma, Adolescents
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).
Detailed description
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. Eligible 12 to 17-year-old patients with asthma controlled on Global Initiative for Asthma (GINA) step 2 medication (ie, low dose inhaled corticosteroid \[ICS\] or leukotriene receptor antagonist \[LTRA\]), as evidenced by an asthma control questionnaire (ACQ-5) score ≤1.5, will be asked to stop their ongoing asthma maintenance treatment. After a washout period (14 to 21 days), all patients with confirmed reversibility will start study treatment, consisting of inhalations of AZD7594 (360 µg, delivered dose, via dry powder inhaler \[DPI\]) once daily for 15 to 16 days. The study intends to include 24 patients in order to have 18 evaluable patients, enrolled in equal proportion in the age group of 12 to 14 years (inclusive), and the age group of 15 to 17 years (inclusive), with at least 7 patients in each subgroup. For each patient, the duration of participation in the study will be approximately 5 to 7 weeks (37 to 52 days)
Interventions
DRUGAZD7594
During treatment period, AZD7594 (360 µg per day) will be administered as oral inhalation via dry powder inhaler or DPI (SD3FL inhaler).
Sponsors
Parexel
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. 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. 2. Patient must be 12 to 17 years of age inclusive, at the time of signing the ICF/assent. 3. 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. 4. Pre-bronchodilator FEV1 ≥70% of the predicted normal value at screening (Visit 1). 5. An ACQ-5 score \<1.5 at screening (Visit 1). 6. Be non-smoker or ex-smoker who has stopped smoking (or using other nicotine products) for \>6 months prior to screening (Visit 1). 7. 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). 8. Male or female 9. Negative pregnancy test (urine or serum) for post-menarcheal female patients at screening (Visit 1). 10. 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. After the washout period, patients are eligible to enter the treatment period only if all of the following inclusion criteria apply: 11. Negative pregnancy test (urine or serum) for post-menarcheal female patients at baseline (Visit 4). 12. 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%).
Exclusion criteria
Patients are eligible to enter the washout period if none of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed plasma concentration at steady state (Cmax,ss) at Day 15 as part of PK evaluation | Pre-dose and 15, 30 minutes, 2, 4, 6, 8, 12 hours post-dose at Day 15 | To assess the PK profile of AZD7594 at steady state following daily inhalations for 2 weeks in adolescent patients with asthma |
| Minimum observed plasma concentration at steady state (Cmin,ss) at Day 15 as part of PK evaluation | Pre-dose and 15, 30 minutes, 2, 4, 6, 8, 12 hours post-dose at Day 15 | To assess the PK profile of AZD7594 at steady state following daily inhalations for 2 weeks in adolescent patients with asthma. |
| Observed trough plasma concentration at end of dosing interval (τ) (Ctrough) at Day 15 as part of PK evaluation | Pre-dose and 15, 30 minutes, 2, 4, 6, 8, 12 hours post-dose at Day 15 | To assess the PK profile of AZD7594 at steady state following daily inhalations for 2 weeks in adolescent patients with asthma |
| Time of maximum observed plasma concentration at steady state (tmax,ss) at Day 15 as part of PK evaluation | Pre-dose and 15, 30 minutes, 2, 4, 6, 8, 12 hours post-dose at Day 15 | To assess the PK profile of AZD7594 at steady state following daily inhalations for 2 weeks in adolescent patients with asthma. |
| Area under the plasma concentration-time curve over a dosing interval (τ) at steady state (AUCτ) at Day 15 as part of PK evaluation | Pre-dose and 15, 30 minutes, 2, 4, 6, 8, 12 hours post-dose at Day 15 | To assess the PK profile of AZD7594 at steady state following daily inhalations for 2 weeks in adolescent patients with asthma. |
| 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 | Pre-dose and 15, 30 minutes, 2, 4, 6, 8, 12 hours post-dose at Day 15 | To assess the PK profile of AZD7594 at steady state following daily inhalations for 2 weeks in adolescent patients with asthma. |
| Apparent total body clearance after extravascular administration at steady state (CLss/F) at Day 15 as part of PK evaluation | Pre-dose and 15, 30 minutes, 2, 4, 6, 8, 12 hours post-dose at Day 15 | To assess the PK profile of AZD7594 at steady state following daily inhalations for 2 weeks in adolescent patients with asthma. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | To evaluate the PD of AZD7594 following daily inhalations for 2 weeks in adolescent patients with asthma. |
| 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 | To evaluate the PD of AZD7594 following daily inhalations for 2 weeks in adolescent patients with asthma. |
| 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) | To evaluate the PD of AZD7594 following daily inhalations for 2 weeks in adolescent patients with asthma. ACQ-5 is a 5 item questionnaire that scores symptoms on a 0-6 scale (where 0=none/no symptoms and 6=worst symptoms) . The form is completed by the patient during visits. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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) | To evaluate the tolerability and safety of inhaled AZD7594 |
Countries
United States
Outcome results
None listed