To Compare the Pharmacokinetics of Budesonide Delivered by BDA MDI to Budesonide Delivered by Pulmicort Respules in Children With Asthma Aged 4 to 8 Years.

Study Overview
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Brief Summary
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To compare the pharmacokinetics of budesonide delivered by BDA MDI to budesonide delivered by Pulmicort Respules in children with Asthma aged 4 to 8 years.

Official Title
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A Phase I, Randomized, Open-label, Single-dose, 2-way Crossover Study to Compare the Pharmacokinetics of Budesonide Delivered by PT027 to Pulmicort Respules® in Children With Asthma Aged 4 to 8 Years (BLANC)

Conditions
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Asthma

Intervention / Treatment
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* Drug: BDA MDI (PT027) 160/180 μg
* Drug: Pulmicort Respules 0.5 MG/ML Inhalation Suspension


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent prior to any study specific procedures. Children should provide assent to join the study, as applicable. The child's parent(s) or legally authorized representative (LAR) must sign the informed consent form (ICF). The LAR must be aged ≥18 years old. Male or female aged between 4 and 8 years inclusive (not having reached his/her 9th birthday by the time of screening). Weigh at least 14 kg or higher. Clinician diagnosed asthma of at least 3 months. Stable on treatment with albuterol PRN and/or ICS and/or leukotriene receptor antagonists (LTRAs) for 2 weeks prior to screening; children taking budesonide in any form at Visit 1 will be switched to another corticosteroid with a washout of budesonide of 3 to 7 days. Demonstrate ability to correctly use the nebulizer and metered-dose inhaler (MDI) device without a spacer. Willingness and ability of the child and parent(s)/LAR to comply with the demands of the study as described in the informed consent/assent. Exclusion Criteria: Inability to change from any budesonide therapy to another suitable corticosteroid. History of life-threatening asthma defined as any asthma episode associated with loss of consciousness, intubation or admission to an intensive care unit. Unstable asthma as judged by the Investigator (eg, any change in asthma therapy within 2 weeks prior to screening or use of more than 2 occasions of rescue medication (albuterol) per day within 1 week prior to screening (potential for rescreen). Children receiving regular maintenance treatment with prohibited anti-inflammatory or long-acting bronchodilator asthma medication (inhaled, nebulized, oral, or systemic) within 1 month prior to screening. More than 1 short course of oral/rectal/systemic corticosteroids within 6 months preceding screening (Visit 1), or any oral/rectal/systemic corticosteroids within 30 days prior to screening. Evidence of active concomitant pulmonary disease other than asthma (children with stable allergic rhinitis will be permitted, as long as, there are no changes in the treatment and the medications do not interfere with the analytical assay methods). Upper respiratory infection involving antibiotic treatment not resolved within 14 days prior to Visit 1. Children with a known or suspected hypersensitivity to albuterol/salbutamol, budesonide or any of the excipients used in the IMPs.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 8 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A/B - Treatment with BDA MDI (PT027) 160/180 μg followed by treatment with Pulmicort Respules 1mg<br>Subjects randomized to receive a single dose of budesonide/albuterol by metered-dose inhaler, BDA MDI, (PT027) 160/180 μg at Visit 2, and a single dose of budesonide by nebulization (Pulmicort Respules) 1mg at Visit 3. | Drug: BDA MDI (PT027) 160/180 μg<br>* Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 80/90 μg per puff. Two puffs to administer 160/180 μg dose.<br>* Other names: PT027;Drug: Pulmicort Respules 0.5 MG/ML Inhalation Suspension<br>* Budesonide 0.5 mg/ml. Each 2 ml Respule contains 1 mg budesonide.<br>|
| Experimental: B/A - Treatment with Pulmicort Respules 1 mg followed by treatment with BDA MDI (PT027) 160/180 μg<br>Subjects randomized to receive a single dose of budesonide by nebulization (Pulmicort Respules) 1mg at Visit 2, and a single dose of budesonide/albuterol by metered-dose inhaler, BDA MDI, (PT027) 160/180 μg at Visit 3. | Drug: BDA MDI (PT027) 160/180 μg<br>* Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 80/90 μg per puff. Two puffs to administer 160/180 μg dose.<br>* Other names: PT027;Drug: Pulmicort Respules 0.5 MG/ML Inhalation Suspension<br>* Budesonide 0.5 mg/ml. Each 2 ml Respule contains 1 mg budesonide.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-t | Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration | A total of 10 samples were taken per treatment visit at pre-dose and at 10, 20, 40, 60, 120, 240, 360, 480 and 720 minutes after dosing. | 
| Cmax | Maximum observed plasma concentration | A total of 10 samples were taken per treatment visit at pre-dose and at 10, 20, 40, 60, 120, 240, 360, 480 and 720 minutes after dosing. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax | Time to reach maximum observed plasma concentration | A total of 10 samples were taken per treatment visit at pre-dose and at 10, 20, 40, 60, 120, 240, 360, 480 and 720 minutes after dosing. | 
| Tlast | Time of last quantifiable plasma concentration | A total of 10 samples were taken per treatment visit at pre-dose and at 10, 20, 40, 60, 120, 240, 360, 480 and 720 minutes after dosing. | 
| Clast | Drug concentration at last observed (quantifiable) concentration | A total of 10 samples were taken per treatment visit at pre-dose and at 10, 20, 40, 60, 120, 240, 360, 480 and 720 minutes after dosing. |