Asthma
Conditions
Keywords
Pediatric, Pharmacokinetics, Budesonide, Formoterol, Symbicort Aerosphere, Symbicort pressurized metered dose inhaler (pMDI)
Brief summary
The purpose of this study is to assess the pharmacokinetics (PK) and safety of symbicort aerosphere and symbicort pressurized metered dose inhaler (pMDI) in participants with asthma aged 4 to less than 12 years.
Detailed description
This is a phase I single-dose, 2-period cross-over, multicenter study in which the participants will be randomized 1:1 to one of two treatment sequences - AB or BA. In the first study period, participants will receive a single dose of either - 1. Treatment A: Symbicort Aerosphere budesonide/formoterol fumarate × 2 puffs (test formulation) 2. Treatment B: Symbicort pMDI budesonide/formoterol fumarate × 2 puffs (reference formulation) After a washout period of at least 28 days and no longer than 42 days, participants who first received Treatment A will receive a single dose of Treatment B, and participants who first received Treatment B will receive a single dose of Treatment A in the study period 2.
Interventions
COMBINATION_PRODUCTBudesonide/formoterol fumarate Aerosphere
Participants will receive budesonide/formoterol fumarate aerosphere as oral inhalations.
COMBINATION_PRODUCTBudesonide/formoterol fumarate pMDI
Participants will receive budesonide/formoterol fumarate pMDI as oral inhalations.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participants who have clinician-diagnosed asthma for at least 3 months. * Body mass index ≤ 95 percentile for age and body weight of at least 15 kg or higher. * Be on a stable dose of one of the following asthma treatments for at least 4 weeks prior to screening (Visit 1): 1. Short-acting β2 agonist (SABA) used as rescue/reliever medication (as needed) only. 2. Low- or medium-dose inhaled corticosteroids (ICS). 3. Leukotriene receptor antagonist (LTRA). 4. Low-dose ICS/long-acting β2-agonist (LABA). 5. Medium-dose ICS/LABA. * Female participants who experience menarche must have a negative urine pregnancy test at screening. Key
Exclusion criteria
* Current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, allergic bronchopulmonary aspergillosis, cystic fibrosis, bronchopulmonary dysplasia, or other severe respiratory abnormalities other than asthma. * History of life-threatening asthma defined as any asthma episode associated with loss of consciousness, intubation or admission to an intensive care unit. * History of severe asthma exacerbation within 8 weeks of Visit 1. * Inability to change from any budesonide therapy to another suitable corticosteroid. * Participants with a known hypersensitivity to budesonide and/or formoterol fumarate or any of the excipients of the product. * Not be able to refrain from consuming alcohol and smoking (including electronic cigarettes, vaping, and marijuana) from the time of screening until after the safety follow-up visit. * Unstable asthma. * Received regular maintenance treatment with prohibited anti-inflammatory or long-acting bronchodilator asthma medication. * Evidence of active liver disease. * Prolonged QT interval corrected for heart rate using Fridericia's correction (QTcF).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed plasma concentration (Cmax) | Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, and 8 hours postdose | To determine and compare the systemic availability (Cmax) of budesonide and formoterol after single doses of Symbicort Aerosphere and Symbicort pMDI in participants 4 to less than 12 years of age with asthma. |
| Area under the plasma concentration-time curve from time 0 to 6 hours postdose (AUC0-6) | Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours and 6 hours postdose | To determine and compare the systemic availability (AUC0-6) of budesonide and formoterol after single doses of Symbicort Aerosphere and Symbicort pMDI in participants 4 to less than 12 years of age with asthma. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to reach peak or maximum observed concentration or response following drug administration (tmax) | Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, and 8 hours postdose | To determine and compare tmax for budesonide and formoterol after single doses of Symbicort Aerosphere and Symbicort pMDI in participants 4 to less than 12 years of age with asthma. |
| Terminal elimination rate constant (λz) | Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, and 8 hours postdose | To determine and compare λz for budesonide and formoterol after single doses of Symbicort Aerosphere and Symbicort pMDI in participants 4 to less than 12 years of age with asthma. |
| Terminal elimination half-life (t½λz) | Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, and 8 hours postdose | To determine and compare t½λz for budesonide and formoterol after single doses of Symbicort Aerosphere and Symbicort pMDI in participants 4 to less than 12 years of age with asthma. |
| Area under plasma concentration-time curve from time 0 to infinity (AUCinf) | Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, and 8 hours postdose | To determine and compare AUCinf for budesonide and formoterol after single doses of Symbicort Aerosphere and Symbicort pMDI in participants 4 to less than 12 years of age with asthma. |
| Mean residence time (MRT) | Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, and 8 hours postdose | To determine and compare MRT for budesonide and formoterol after single doses of Symbicort Aerosphere and Symbicort pMDI in participants 4 to less than 12 years of age with asthma. |
| Apparent total body clearance (CL/F) | Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, and 8 hours postdose | To determine and compare CL/F for budesonide and formoterol after single doses of Symbicort Aerosphere and Symbicort pMDI in participants 4 to less than 12 years of age with asthma. |
| Apparent volume of distribution based on the terminal phase (Vz/F) | Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, and 8 hours postdose | To determine and compare Vz/F for budesonide and formoterol after single doses of Symbicort Aerosphere and Symbicort pMDI in participants 4 to less than 12 years of age with asthma. |
| Number of participants with adverse events | From Screening (Day -14 to Day -1) to Follow-up telephone call (approximately 7 weeks) | To assess the safety and tolerability of single doses of Symbicort Aerosphere and Symbicort pMDI in participants 4 to less than 12 years of age with asthma. |
| Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast) | Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, and 8 hours postdose | To determine and compare AUClast for budesonide and formoterol after single doses of Symbicort Aerosphere and Symbicort pMDI in participants 4 to less than 12 years of age with asthma. |
Countries
United States
Outcome results
None listed