BLANC: 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.
Sponsor
Bond Avillion 2 Development LP (Industry)
Overall Status
Completed
CT.gov ID
NCT04848662
Collaborator
(none)
12
2
2
2.1
6
2.9
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
12 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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)
Actual Study Start Date
:
May 6, 2021
Actual Primary Completion Date
:
Jul 5, 2021
Actual Study Completion Date
:
Jul 8, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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, and a single dose of budesonide by nebulization (Pulmicort Respules) 1mg at Visit 3. |
Drug: 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.
Other Names:
Drug: Pulmicort Respules 0.5 MG/ML Inhalation Suspension
Budesonide 0.5 mg/ml. Each 2 ml Respule contains 1 mg budesonide.
|
| Experimental: 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. |
Drug: 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.
Other Names:
Drug: Pulmicort Respules 0.5 MG/ML Inhalation Suspension
Budesonide 0.5 mg/ml. Each 2 ml Respule contains 1 mg budesonide.
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
Secondary Outcome Measures
- 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
Eligibility Criteria
Criteria
Ages Eligible for Study:
4 Years
to 8 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | IPS Research | Oklahoma City | Oklahoma | United States | 73106 |
| 2 | TTS Research | Boerne | Texas | United States | 78006 |
Sponsors and Collaborators
- Bond Avillion 2 Development LP
Investigators
- Study Director: Frank Albers, MD, PhD, Avillion LLP
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Bond Avillion 2 Development LP
ClinicalTrials.gov Identifier:
NCT04848662
Other Study ID Numbers:
- AV006
First Posted:
Apr 19, 2021
Last Update Posted:
May 11, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
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 Detail | 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). |
| Arm/Group Title | 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 |
|---|---|---|
| Arm/Group Description | 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. | 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 Title: Period 1 (First Treatment Intervention) | ||
| STARTED | 6 | 6 |
| COMPLETED | 6 | 6 |
| NOT COMPLETED | 0 | 0 |
| Period Title: Period 1 (First Treatment Intervention) | ||
| STARTED | 6 | 6 |
| COMPLETED | 5 | 6 |
| NOT COMPLETED | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | 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 |
|---|---|---|---|
| Arm/Group Description | 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. | 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 of all reporting groups |
| Overall Participants | 6 | 6 | 12 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
5.8
(1.72)
|
6.5
(1.64)
|
6.2
(1.64)
|
| Age, Customized (Count of Participants) | |||
| >= 4 to < 6 |
3
50%
|
2
33.3%
|
5
41.7%
|
| >= 6 to <9 |
3
50%
|
4
66.7%
|
7
58.3%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
6
100%
|
3
50%
|
9
75%
|
| Male |
0
0%
|
3
50%
|
3
25%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
2
33.3%
|
3
50%
|
5
41.7%
|
| Not Hispanic or Latino |
4
66.7%
|
3
50%
|
7
58.3%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
16.7%
|
2
33.3%
|
3
25%
|
| White |
4
66.7%
|
4
66.7%
|
8
66.7%
|
| More than one race |
1
16.7%
|
0
0%
|
1
8.3%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
6
100%
|
6
100%
|
12
100%
|
| Height (Centimeters (cm)) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Centimeters (cm)] |
118.22
(15.678)
|
123.42
(13.939)
|
120.82
(14.402)
|
| Weight (Kilograms (kg)) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Kilograms (kg)] |
26.22
(10.270)
|
34.77
(12.430)
|
30.49
(11.752)
|
| Body Mass Index (Kilograms per meter squared) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Kilograms per meter squared] |
17.97
(2.641)
|
22.07
(3.269)
|
20.02
(3.551)
|
Outcome Measures
| Title | AUC0-t |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects | Treatment Intervention B - Pulmicort Respules 1 mg |
|---|---|---|
| Arm/Group Description | Individual PK parameters and summary statistics after administration of study treatment A - BDA MDI (PT027) 160/180 μg | Individual PK parameters and summary statistics after administration of study treatment B - Pulmicort Respules 1mg |
| Measure Participants | 11 | 10 |
| Mean (Standard Deviation) [h*pg/mL] |
435
(191)
|
1164
(587)
|
| Title | Cmax |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects | Treatment Intervention B - Pulmicort Respules 1 mg |
|---|---|---|
| Arm/Group Description | Individual PK parameters and summary statistics after administration of study treatment A - BDA MDI (PT027) 160/180 μg | Individual PK parameters and summary statistics after administration of study treatment B - Pulmicort Respules 1mg |
| Measure Participants | 11 | 10 |
| Mean (Standard Deviation) [pg/mL] |
126
(53.3)
|
651
(480)
|
| Title | Tmax |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects | Treatment Intervention B - Pulmicort Respules 1 mg |
|---|---|---|
| Arm/Group Description | Individual PK parameters and summary statistics after administration of study treatment A - BDA MDI (PT027) 160/180 μg | Individual PK parameters and summary statistics after administration of study treatment B - Pulmicort Respules 1mg |
| Measure Participants | 11 | 10 |
| Median (Full Range) [hours] |
0.667
|
0.167
|
| Title | Tlast |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects | Treatment Intervention B - Pulmicort Respules 1 mg |
|---|---|---|
| Arm/Group Description | Individual PK parameters and summary statistics after administration of study treatment A - BDA MDI (PT027) 160/180 μg | Individual PK parameters and summary statistics after administration of study treatment B - Pulmicort Respules 1mg |
| Measure Participants | 11 | 10 |
| Median (Full Range) [hours] |
12.0
|
12.0
|
| Title | Clast |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects | Treatment Intervention B - Pulmicort Respules 1 mg |
|---|---|---|
| Arm/Group Description | Individual PK parameters and summary statistics after administration of study treatment A - BDA MDI (PT027) 160/180 μg | Individual PK parameters and summary statistics after administration of study treatment B - Pulmicort Respules 1mg |
| Measure Participants | 11 | 10 |
| Mean (Standard Deviation) [pg/mL] |
12.5
(5.03)
|
18.7
(7.09)
|
Adverse Events
| Time Frame | Approximately one week for each treatment intervention. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Safety population included all subjects who received at least one treatment intervention. | |||
| Arm/Group Title | Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects | Treatment Intervention B - Pulmicort Respules 1 mg | ||
| Arm/Group Description | Safety analysis of subjects receiving Treatment A - BDA MDI (PT027) 160/180 μg | Safety analysis of subjects receiving Treatment B - Pulmicort Respules 1mg | ||
All Cause Mortality |
||||
| Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects | Treatment Intervention B - Pulmicort Respules 1 mg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/12 (0%) | ||
Serious Adverse Events |
||||
| Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects | Treatment Intervention B - Pulmicort Respules 1 mg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/12 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Treatment Intervention - BDA MDI (PT027) 160/180 μg - All Subjects | Treatment Intervention B - Pulmicort Respules 1 mg | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 1/12 (8.3%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Miliaria | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
data or results obtained from this study must not be published without prior approval from the Sponsor.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Avillion LLP |
| Phone | +44 (0)203 764 9530 |
| avillion@avillionllp.com |
Responsible Party:
Bond Avillion 2 Development LP
ClinicalTrials.gov Identifier:
NCT04848662
Other Study ID Numbers:
- AV006
First Posted:
Apr 19, 2021
Last Update Posted:
May 11, 2022
Last Verified:
Apr 1, 2022