Asthma
Conditions
Brief summary
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.
Interventions
DRUGBDA MDI (PT027) 160/180 μg
Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 80/90 μg per puff. Two puffs to administer 160/180 μg dose.
DRUGPulmicort Respules 0.5 MG/ML Inhalation Suspension
Budesonide 0.5 mg/ml. Each 2 ml Respule contains 1 mg budesonide.
Sponsors
Bond Avillion 2 Development LP
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 8 Years
Healthy volunteers
No
Inclusion criteria
1. 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. 2. Male or female aged between 4 and 8 years inclusive (not having reached his/her 9th birthday by the time of screening). 3. Weigh at least 14 kg or higher. 4. Clinician diagnosed asthma of at least 3 months. 5. 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. 6. Demonstrate ability to correctly use the nebulizer and metered-dose inhaler (MDI) device without a spacer. 7. 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
1. Inability to change from any budesonide therapy to another suitable corticosteroid. 2. History of life-threatening asthma defined as any asthma episode associated with loss of consciousness, intubation or admission to an intensive care unit. 3. 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). 4. 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. 5. 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. 6. 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). 7. Upper respiratory infection involving antibiotic treatment not resolved within 14 days prior to Visit 1. 8. Children with a known or suspected hypersensitivity to albuterol/salbutamol, budesonide or any of the excipients used in the IMPs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | 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. | Maximum observed plasma concentration |
| AUC0-t | 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. | Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax | 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. | Time to reach maximum observed plasma concentration |
| Tlast | 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. | Time of last quantifiable plasma concentration |
| Clast | 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. | Drug concentration at last observed (quantifiable) concentration |
Countries
United States
Participant flow
Recruitment details
The target population consisted of male or female children aged between 4 and 8 years who had clinician-diagnosed asthma of at least 3 months. Subjects were expected to be stable on treatment with albuterol as needed and/or inhaled corticosteroids and/or leukotriene receptor antagonists for 2 weeks prior to screening. The first subject enrolled on 06 May 2021 and the last subject completed the study on 08 July 2021. Subjects were enrolled at 2 US study centers.
Pre-assignment details
The randomized treatment phase started after a screening period with a maximum duration of 14 days. Subjects who were taking budesonide in any form at Visit 1 were switched to another corticosteroid with a washout of budesonide of 3 to 7 days. In addition to the 12 subjects randomized, 1 subject was screened but did not participate (1 screen failure).
Participants by arm
| Arm | Count |
|---|---|
| A/B - Treatment With BDA MDI (PT027) 160/180 μg Followed by Treatment With Pulmicort Respules 1mg Subjects randomized to receive a single dose of budesonide/albuterol by metered-dose inhaler, BDA MDI, (PT027) 160/180 μg at Visit 2/Period 1, and a single dose of budesonide by nebulization (Pulmicort Respules) 1mg at Visit 3/Period 2.
Visit 2/Period 1 (Day 1) - BDA MDI (PT027) 160/180 μg: Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 80/90 μg per puff. Two puffs to administer 160/180 μg dose.
Visit 3/Period 2 (Day 8 +/- 6 days) - Pulmicort Respules 0.5 mg/mL inhalation suspension: Budesonide 0.5 mg/ml. Each 2 ml Respule contains 1 mg budesonide. | 6 |
| B/A - Treatment With Pulmicort Respules 1 mg Followed by Treatment With BDA MDI (PT027) 160/180 μg 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.
Visit 2/Period 1 (Day 1) - Pulmicort Respules 0.5 MG/ML Inhalation Suspension: Budesonide 0.5 mg/ml. Each 2 ml Respule contains 1 mg budesonide.
Visit 3/Period 2 (Day 8 +/- 6 days) - BDA MDI (PT027) 160/180 μg: Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 80/90 μg per puff. Two puffs to administer 160/180 μg dose. | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 2 (Second Treatment Intervention) | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | A/B - Treatment With BDA MDI (PT027) 160/180 μg Followed by Treatment With Pulmicort Respules 1mg | B/A - Treatment With Pulmicort Respules 1 mg Followed by Treatment With BDA MDI (PT027) 160/180 μg | Total |
|---|---|---|---|
| Age, Continuous | 5.8 years STANDARD_DEVIATION 1.72 | 6.5 years STANDARD_DEVIATION 1.64 | 6.2 years STANDARD_DEVIATION 1.64 |
| Age, Customized Age group (years) >= 4 to < 6 | 3 Participants | 2 Participants | 5 Participants |
| Age, Customized Age group (years) >= 6 to <9 | 3 Participants | 4 Participants | 7 Participants |
| Body Mass Index | 17.97 Kilograms per meter squared STANDARD_DEVIATION 2.641 | 22.07 Kilograms per meter squared STANDARD_DEVIATION 3.269 | 20.02 Kilograms per meter squared STANDARD_DEVIATION 3.551 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 3 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 118.22 Centimeters (cm) STANDARD_DEVIATION 15.678 | 123.42 Centimeters (cm) STANDARD_DEVIATION 13.939 | 120.82 Centimeters (cm) STANDARD_DEVIATION 14.402 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 4 Participants | 8 Participants |
| Region of Enrollment United States | 6 participants | 6 participants | 12 participants |
| Sex: Female, Male Female | 6 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 0 Participants | 3 Participants | 3 Participants |
| Weight | 26.22 Kilograms (kg) STANDARD_DEVIATION 10.27 | 34.77 Kilograms (kg) STANDARD_DEVIATION 12.43 | 30.49 Kilograms (kg) STANDARD_DEVIATION 11.752 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 12 | 1 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
AUC0-t
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration
Time frame: 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.
Population: Budesonide PK samples were available from 12 children. There were 2 instances, one for each treatment intervention, where the pre-dose budesonide concentration was considered too high (16% and 46% of Cmax), potentially having an impact on the post-dose concentrations. There was also 1 instance in the Pulmicort Respules 1mg treatment intervention where post-dose samples were not collected due to difficulty with the catheter. PK parameters were not calculated in these three instances.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects | AUC0-t | 435 h*pg/mL | Standard Deviation 191 |
| Treatment Intervention B - Pulmicort Respules 1 mg | AUC0-t | 1164 h*pg/mL | Standard Deviation 587 |
Primary
Cmax
Maximum observed plasma concentration
Time frame: 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.
Population: Budesonide PK samples were available from 12 children. There were 2 instances, one for each treatment intervention, where the pre-dose budesonide concentration was considered too high (16% and 46% of Cmax), potentially having an impact on the post-dose concentrations. There was also 1 instance in the Pulmicort Respules 1mg treatment intervention where post-dose samples were not collected due to difficulty with the catheter. PK parameters were not calculated in these three instances.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects | Cmax | 126 pg/mL | Standard Deviation 53.3 |
| Treatment Intervention B - Pulmicort Respules 1 mg | Cmax | 651 pg/mL | Standard Deviation 480 |
Secondary
Clast
Drug concentration at last observed (quantifiable) concentration
Time frame: 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.
Population: Budesonide PK samples were available from 12 children. There were 2 instances, one for each treatment intervention, where the pre-dose budesonide concentration was considered too high (16% and 46% of Cmax), potentially having an impact on the post-dose concentrations. There was also 1 instance in the Pulmicort Respules 1mg treatment intervention where post-dose samples were not collected due to difficulty with the catheter. PK parameters were not calculated in these three instances.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects | Clast | 12.5 pg/mL | Standard Deviation 5.03 |
| Treatment Intervention B - Pulmicort Respules 1 mg | Clast | 18.7 pg/mL | Standard Deviation 7.09 |
Secondary
Tlast
Time of last quantifiable plasma concentration
Time frame: 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.
Population: Budesonide PK samples were available from 12 children. There were 2 instances, one for each treatment intervention, where the pre-dose budesonide concentration was considered too high (16% and 46% of Cmax), potentially having an impact on the post-dose concentrations. There was also 1 instance in the Pulmicort Respules 1mg treatment intervention where post-dose samples were not collected due to difficulty with the catheter. PK parameters were not calculated in these three instances.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects | Tlast | 12.0 hours |
| Treatment Intervention B - Pulmicort Respules 1 mg | Tlast | 12.0 hours |
Secondary
Tmax
Time to reach maximum observed plasma concentration
Time frame: 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.
Population: Budesonide PK samples were available from 12 children. There were 2 instances, one for each treatment intervention, where the pre-dose budesonide concentration was considered too high (16% and 46% of Cmax), potentially having an impact on the post-dose concentrations. There was also 1 instance in the Pulmicort Respules 1mg treatment intervention where post-dose samples were not collected due to difficulty with the catheter. PK parameters were not calculated in these three instances.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects | Tmax | 0.667 hours |
| Treatment Intervention B - Pulmicort Respules 1 mg | Tmax | 0.167 hours |