Trial Outcomes & Findings for 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. (NCT NCT04848662)
NCT ID: NCT04848662
Last Updated: 2022-05-11
Results Overview
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration
COMPLETED
PHASE1
12 participants
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.
2022-05-11
Participant Flow
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.
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).
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Period 1 (First Treatment Intervention)
STARTED
|
6
|
6
|
|
Period 1 (First Treatment Intervention)
COMPLETED
|
6
|
6
|
|
Period 1 (First Treatment Intervention)
NOT COMPLETED
|
0
|
0
|
|
Period 2 (Second Treatment Intervention)
STARTED
|
6
|
6
|
|
Period 2 (Second Treatment Intervention)
COMPLETED
|
5
|
6
|
|
Period 2 (Second Treatment Intervention)
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Period 2 (Second Treatment Intervention)
Physician Decision
|
1
|
0
|
Baseline Characteristics
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.
Baseline characteristics by cohort
| Measure |
A/B - Treatment With BDA MDI (PT027) 160/180 μg Followed by Treatment With Pulmicort Respules 1mg
n=6 Participants
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.
|
B/A - Treatment With Pulmicort Respules 1 mg Followed by Treatment With BDA MDI (PT027) 160/180 μg
n=6 Participants
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.
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
5.8 years
STANDARD_DEVIATION 1.72 • n=5 Participants
|
6.5 years
STANDARD_DEVIATION 1.64 • n=7 Participants
|
6.2 years
STANDARD_DEVIATION 1.64 • n=5 Participants
|
|
Age, Customized
Age group (years) · >= 4 to < 6
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Age, Customized
Age group (years) · >= 6 to <9
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=5 Participants
|
6 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Height
|
118.22 Centimeters (cm)
STANDARD_DEVIATION 15.678 • n=5 Participants
|
123.42 Centimeters (cm)
STANDARD_DEVIATION 13.939 • n=7 Participants
|
120.82 Centimeters (cm)
STANDARD_DEVIATION 14.402 • n=5 Participants
|
|
Weight
|
26.22 Kilograms (kg)
STANDARD_DEVIATION 10.270 • n=5 Participants
|
34.77 Kilograms (kg)
STANDARD_DEVIATION 12.430 • n=7 Participants
|
30.49 Kilograms (kg)
STANDARD_DEVIATION 11.752 • n=5 Participants
|
|
Body Mass Index
|
17.97 Kilograms per meter squared
STANDARD_DEVIATION 2.641 • n=5 Participants
|
22.07 Kilograms per meter squared
STANDARD_DEVIATION 3.269 • n=7 Participants
|
20.02 Kilograms per meter squared
STANDARD_DEVIATION 3.551 • n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration
Outcome measures
| Measure |
Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects
n=11 Participants
Individual PK parameters and summary statistics after administration of study treatment A - BDA MDI (PT027) 160/180 μg
|
Treatment Intervention B - Pulmicort Respules 1 mg
n=10 Participants
Individual PK parameters and summary statistics after administration of study treatment B - Pulmicort Respules 1mg
|
|---|---|---|
|
AUC0-t
|
435 h*pg/mL
Standard Deviation 191
|
1164 h*pg/mL
Standard Deviation 587
|
PRIMARY outcome
Timeframe: 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.
Maximum observed plasma concentration
Outcome measures
| Measure |
Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects
n=11 Participants
Individual PK parameters and summary statistics after administration of study treatment A - BDA MDI (PT027) 160/180 μg
|
Treatment Intervention B - Pulmicort Respules 1 mg
n=10 Participants
Individual PK parameters and summary statistics after administration of study treatment B - Pulmicort Respules 1mg
|
|---|---|---|
|
Cmax
|
126 pg/mL
Standard Deviation 53.3
|
651 pg/mL
Standard Deviation 480
|
SECONDARY outcome
Timeframe: 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.
Time to reach maximum observed plasma concentration
Outcome measures
| Measure |
Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects
n=11 Participants
Individual PK parameters and summary statistics after administration of study treatment A - BDA MDI (PT027) 160/180 μg
|
Treatment Intervention B - Pulmicort Respules 1 mg
n=10 Participants
Individual PK parameters and summary statistics after administration of study treatment B - Pulmicort Respules 1mg
|
|---|---|---|
|
Tmax
|
0.667 hours
Interval 0.333 to 2.0
|
0.167 hours
Interval 0.167 to 0.75
|
SECONDARY outcome
Timeframe: 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.
Time of last quantifiable plasma concentration
Outcome measures
| Measure |
Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects
n=11 Participants
Individual PK parameters and summary statistics after administration of study treatment A - BDA MDI (PT027) 160/180 μg
|
Treatment Intervention B - Pulmicort Respules 1 mg
n=10 Participants
Individual PK parameters and summary statistics after administration of study treatment B - Pulmicort Respules 1mg
|
|---|---|---|
|
Tlast
|
12.0 hours
Interval 8.0 to 12.0
|
12.0 hours
Interval 11.9 to 12.0
|
SECONDARY outcome
Timeframe: 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.
Drug concentration at last observed (quantifiable) concentration
Outcome measures
| Measure |
Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects
n=11 Participants
Individual PK parameters and summary statistics after administration of study treatment A - BDA MDI (PT027) 160/180 μg
|
Treatment Intervention B - Pulmicort Respules 1 mg
n=10 Participants
Individual PK parameters and summary statistics after administration of study treatment B - Pulmicort Respules 1mg
|
|---|---|---|
|
Clast
|
12.5 pg/mL
Standard Deviation 5.03
|
18.7 pg/mL
Standard Deviation 7.09
|
Adverse Events
Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects
Treatment Intervention B - Pulmicort Respules 1 mg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects
n=12 participants at risk
Safety analysis of subjects receiving Treatment A - BDA MDI (PT027) 160/180 μg
|
Treatment Intervention B - Pulmicort Respules 1 mg
n=12 participants at risk
Safety analysis of subjects receiving Treatment B - Pulmicort Respules 1mg
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Miliaria
|
0.00%
0/12 • Approximately one week for each treatment intervention.
Safety population included all subjects who received at least one treatment intervention.
|
8.3%
1/12 • Number of events 1 • Approximately one week for each treatment intervention.
Safety population included all subjects who received at least one treatment intervention.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee data or results obtained from this study must not be published without prior approval from the Sponsor.
- Publication restrictions are in place
Restriction type: OTHER