Trial Outcomes & Findings for A Study to Assess the Total Systemic Exposure Bioequivalence of of Budesonide, Glycopyrronium, and Formoterol Delivered by BGF MDI With Next-Generation Propellant Compared With BGF MDI With HFA Propellant (NCT NCT05569421)
NCT ID: NCT05569421
Last Updated: 2025-08-22
Results Overview
The AUCinf of budesonide, glycopryrronium and formoterol in participants was evaluated.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
108 participants
Primary outcome timeframe
Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)
Results posted on
2025-08-22
Participant Flow
This study was conducted in one study center in the US.
The screening period was of 4 weeks. All the study assessments were performed as per the schedule of assessments. Participants who met the eligibility criteria were randomized to study intervention.
Participant milestones
| Measure |
Treatment Sequence ABB
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment Sequence BAB
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment Sequence BBA
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
|---|---|---|---|
|
Overall Study
STARTED
|
36
|
36
|
36
|
|
Overall Study
COMPLETED
|
35
|
36
|
36
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
Treatment Sequence ABB
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment Sequence BAB
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment Sequence BBA
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
Baseline Characteristics
A Study to Assess the Total Systemic Exposure Bioequivalence of of Budesonide, Glycopyrronium, and Formoterol Delivered by BGF MDI With Next-Generation Propellant Compared With BGF MDI With HFA Propellant
Baseline characteristics by cohort
| Measure |
Treatment Sequence ABB
n=36 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment Sequence BAB
n=36 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment Sequence BBA
n=36 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Total
n=108 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
36.0 Years
STANDARD_DEVIATION 10.0 • n=5 Participants
|
35.8 Years
STANDARD_DEVIATION 9.6 • n=7 Participants
|
39.5 Years
STANDARD_DEVIATION 11.2 • n=5 Participants
|
37.1 Years
STANDARD_DEVIATION 10.3 • n=4 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
49 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
59 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
21 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
60 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
26 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Other
|
3 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)Population: The pharmacokinetic (PK) analysis set consisted of all participants in the safety analysis set for whom at least one primary PK parameter could be calculated and who had no IPDs or AEs thought to impact the analysis of the PK data. Here, N = number of participants analyzed refers to n = number analyzed for this outcome measure at specific timepoints.
The AUCinf of budesonide, glycopryrronium and formoterol in participants was evaluated.
Outcome measures
| Measure |
Treatment B (Replicate 2)
n=107 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment A
n=108 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment B (Replicate 1)
n=107 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
|---|---|---|---|
|
Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf)
Budesonide
|
4012 hour*picogram/milliliter (h*pg/mL)
Geometric Coefficient of Variation 46.01
|
4047 hour*picogram/milliliter (h*pg/mL)
Geometric Coefficient of Variation 46.71
|
4112 hour*picogram/milliliter (h*pg/mL)
Geometric Coefficient of Variation 40.78
|
|
Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf)
Glycopyronium
|
120.9 hour*picogram/milliliter (h*pg/mL)
Geometric Coefficient of Variation 83.40
|
85.62 hour*picogram/milliliter (h*pg/mL)
Geometric Coefficient of Variation 94.55
|
81.10 hour*picogram/milliliter (h*pg/mL)
Geometric Coefficient of Variation 78.85
|
|
Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf)
Formoterol
|
125.0 hour*picogram/milliliter (h*pg/mL)
Geometric Coefficient of Variation 40.55
|
124.3 hour*picogram/milliliter (h*pg/mL)
Geometric Coefficient of Variation 43.80
|
121.3 hour*picogram/milliliter (h*pg/mL)
Geometric Coefficient of Variation 41.19
|
PRIMARY outcome
Timeframe: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)Population: The PK analysis set consisted of all participants in the safety analysis set for whom at least one primary PK parameter could be calculated and who had no IPDs or AEs thought to impact the analysis of the PK data. Here, N = number of participants analyzed refers to n = number analyzed for this outcome measure at specific timepoints.
The AUClast of budesonide, glycopryrronium and formoterol in participants was evaluated.
Outcome measures
| Measure |
Treatment B (Replicate 2)
n=104 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment A
n=105 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment B (Replicate 1)
n=103 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
|---|---|---|---|
|
Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast)
Budesonide
|
3905 h*pg/mL
Geometric Coefficient of Variation 46.82
|
3943 h*pg/mL
Geometric Coefficient of Variation 47.60
|
4003 h*pg/mL
Geometric Coefficient of Variation 40.66
|
|
Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast)
Glycopyrronium
|
63.29 h*pg/mL
Geometric Coefficient of Variation 72.90
|
52.68 h*pg/mL
Geometric Coefficient of Variation 52.68
|
49.31 h*pg/mL
Geometric Coefficient of Variation 84.38
|
|
Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast)
Formoterol
|
103.9 h*pg/mL
Geometric Coefficient of Variation 42.47
|
102.5 h*pg/mL
Geometric Coefficient of Variation 48.47
|
100.3 h*pg/mL
Geometric Coefficient of Variation 45.89
|
PRIMARY outcome
Timeframe: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)Population: The PK analysis set consisted of all participants in the safety analysis set for whom at least one primary PK parameter could be calculated and who had no IPDs or AEs thought to impact the analysis of the PK data. Here, N = number of participants analyzed refers to n = number analyzed for this outcome measure at specific timepoints.
The Cmax of budesonide, glycopryrronium and formoterol in participants was evaluated.
Outcome measures
| Measure |
Treatment B (Replicate 2)
n=104 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment A
n=105 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment B (Replicate 1)
n=103 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
|---|---|---|---|
|
Maximum Observed Plasma (Peak) Drug Concentration (Cmax)
Budesonide
|
1146 picograms per milliliter (pg/mL)
Geometric Coefficient of Variation 65.91
|
1124 picograms per milliliter (pg/mL)
Geometric Coefficient of Variation 65.67
|
1143 picograms per milliliter (pg/mL)
Geometric Coefficient of Variation 60.79
|
|
Maximum Observed Plasma (Peak) Drug Concentration (Cmax)
Glycopyrronium
|
19.70 picograms per milliliter (pg/mL)
Geometric Coefficient of Variation 87.52
|
17.09 picograms per milliliter (pg/mL)
Geometric Coefficient of Variation 90.52
|
20.41 picograms per milliliter (pg/mL)
Geometric Coefficient of Variation 87.46
|
|
Maximum Observed Plasma (Peak) Drug Concentration (Cmax)
Formoterol
|
26.12 picograms per milliliter (pg/mL)
Geometric Coefficient of Variation 54.39
|
23.48 picograms per milliliter (pg/mL)
Geometric Coefficient of Variation 60.12
|
24.54 picograms per milliliter (pg/mL)
Geometric Coefficient of Variation 62.22
|
SECONDARY outcome
Timeframe: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)Population: The PK analysis set consisted of all participants in the safety analysis set for whom at least one primary PK parameter could be calculated and who had no IPDs or AEs thought to impact the analysis of the PK data. Here, N = number of participants analyzed refers to n = number analyzed for this outcome measure at specific timepoints.
The tmax of budesonide, glycopryrronium and formoterol in participants was evaluated.
Outcome measures
| Measure |
Treatment B (Replicate 2)
n=104 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment A
n=105 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment B (Replicate 1)
n=103 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
|---|---|---|---|
|
Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax)
Budesonide
|
0.33 Hours
Interval 0.07 to 2.05
|
0.35 Hours
Interval 0.08 to 2.0
|
0.33 Hours
Interval 0.08 to 2.02
|
|
Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax)
Glycopyrronium
|
0.03 Hours
Interval 0.02 to 4.02
|
0.03 Hours
Interval 0.02 to 4.13
|
0.03 Hours
Interval 0.03 to 2.02
|
|
Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax)
Formoterol
|
0.08 Hours
Interval 0.03 to 2.12
|
0.08 Hours
Interval 0.03 to 4.02
|
0.08 Hours
Interval 0.03 to 2.03
|
SECONDARY outcome
Timeframe: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)Population: The PK analysis set consisted of all participants in the safety analysis set for whom at least one primary PK parameter could be calculated and who had no IPDs or AEs thought to impact the analysis of the PK data. Here, N = number of participants analyzed refers to n = number analyzed for this outcome measure at specific timepoints.
The λz of budesonide, glycopryrronium and formoterol in participants was evaluated.
Outcome measures
| Measure |
Treatment B (Replicate 2)
n=104 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment A
n=105 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment B (Replicate 1)
n=103 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
|---|---|---|---|
|
Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz)
Budesonide
|
0.1500 1/hour
Geometric Coefficient of Variation 24.99
|
0.1508 1/hour
Geometric Coefficient of Variation 25.19
|
0.1538 1/hour
Geometric Coefficient of Variation 25.24
|
|
Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz)
Glycopyrronium
|
0.03853 1/hour
Geometric Coefficient of Variation 100.5
|
0.05906 1/hour
Geometric Coefficient of Variation 97.13
|
0.06010 1/hour
Geometric Coefficient of Variation 92.16
|
|
Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz)
Formoterol
|
0.08625 1/hour
Geometric Coefficient of Variation 39.39
|
0.08911 1/hour
Geometric Coefficient of Variation 36.39
|
0.08926 1/hour
Geometric Coefficient of Variation 36.50
|
SECONDARY outcome
Timeframe: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)Population: The PK analysis set consisted of all participants in the safety analysis set for whom at least one primary PK parameter could be calculated and who had no IPDs or AEs thought to impact the analysis of the PK data. Here, N = number of participants analyzed refers to n = number analyzed for this outcome measure at specific timepoints.
The t½λz of budesonide, glycopryrronium and formoterol in participants was evaluated.
Outcome measures
| Measure |
Treatment B (Replicate 2)
n=104 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment A
n=105 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment B (Replicate 1)
n=103 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
|---|---|---|---|
|
Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz)
Budesonide
|
4.622 Hours
Geometric Coefficient of Variation 24.99
|
4.596 Hours
Geometric Coefficient of Variation 25.19
|
4.506 Hours
Geometric Coefficient of Variation 25.24
|
|
Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz)
Glycopyrronium
|
17.99 Hours
Geometric Coefficient of Variation 100.5
|
11.74 Hours
Geometric Coefficient of Variation 97.13
|
11.53 Hours
Geometric Coefficient of Variation 92.16
|
|
Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz)
Formoterol
|
8.037 Hours
Geometric Coefficient of Variation 39.39
|
7.779 Hours
Geometric Coefficient of Variation 36.39
|
7.766 Hours
Geometric Coefficient of Variation 36.50
|
SECONDARY outcome
Timeframe: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)Population: The PK analysis set consisted of all participants in the safety analysis set for whom at least one primary PK parameter could be calculated and who had no IPDs or AEs thought to impact the analysis of the PK data. Here, N = number of participants analyzed refers to n = number analyzed for this outcome measure at specific timepoints.
The MRTinf of budesonide, glycopryrronium and formoterol in participants was evaluated.
Outcome measures
| Measure |
Treatment B (Replicate 2)
n=104 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment A
n=105 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment B (Replicate 1)
n=103 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
|---|---|---|---|
|
Mean Residence Time of the Unchanged Drug in the Systemic Circulation From Zero to Infinity (MRTinf)
Budesonide
|
4.924 Hours
Geometric Coefficient of Variation 19.98
|
4.855 Hours
Geometric Coefficient of Variation 21.37
|
4.893 Hours
Geometric Coefficient of Variation 24.30
|
|
Mean Residence Time of the Unchanged Drug in the Systemic Circulation From Zero to Infinity (MRTinf)
Glycopyrronium
|
24.50 Hours
Geometric Coefficient of Variation 96.84
|
16.02 Hours
Geometric Coefficient of Variation 93.66
|
15.56 Hours
Geometric Coefficient of Variation 86.14
|
|
Mean Residence Time of the Unchanged Drug in the Systemic Circulation From Zero to Infinity (MRTinf)
Formoterol
|
10.62 Hours
Geometric Coefficient of Variation 33.34
|
10.48 Hours
Geometric Coefficient of Variation 29.28
|
10.38 Hours
Geometric Coefficient of Variation 30.42
|
SECONDARY outcome
Timeframe: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)Population: The PK analysis set consisted of all participants in the safety analysis set for whom at least one primary PK parameter could be calculated and who had no IPDs or AEs thought to impact the analysis of the PK data. Here, N = number of participants analyzed refers to n = number analyzed for this outcome measure at specific timepoints.
The CL/F of budesonide, glycopryrronium and formoterol in participants was evaluated.
Outcome measures
| Measure |
Treatment B (Replicate 2)
n=104 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment A
n=105 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment B (Replicate 1)
n=103 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
|---|---|---|---|
|
Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)
Budesonide
|
159.5 Liters/hour (L/h)
Geometric Coefficient of Variation 46.01
|
158.2 Liters/hour (L/h)
Geometric Coefficient of Variation 46.71
|
155.6 Liters/hour (L/h)
Geometric Coefficient of Variation 40.78
|
|
Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)
Glycopyrronium
|
238.2 Liters/hour (L/h)
Geometric Coefficient of Variation 83.40
|
336.4 Liters/hour (L/h)
Geometric Coefficient of Variation 94.55
|
355.1 Liters/hour (L/h)
Geometric Coefficient of Variation 78.85
|
|
Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)
Formoterol
|
153.6 Liters/hour (L/h)
Geometric Coefficient of Variation 40.55
|
154.5 Liters/hour (L/h)
Geometric Coefficient of Variation 43.80
|
158.2 Liters/hour (L/h)
Geometric Coefficient of Variation 41.19
|
SECONDARY outcome
Timeframe: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)Population: The PK analysis set consisted of all participants in the safety analysis set for whom at least one primary PK parameter could be calculated and who had no IPDs or AEs thought to impact the analysis of the PK data. Here, N = number of participants analyzed refers to n = number analyzed for this outcome measure at specific timepoints.
The Vz/F of budesonide, glycopryrronium and formoterol in participants was evaluated.
Outcome measures
| Measure |
Treatment B (Replicate 2)
n=104 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment A
n=105 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment B (Replicate 1)
n=103 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
|---|---|---|---|
|
Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on Terminal Phase) (Vz/F)
Budesonide
|
1064 Liters (L)
Geometric Coefficient of Variation 45.06
|
1049 Liters (L)
Geometric Coefficient of Variation 47.84
|
1012 Liters (L)
Geometric Coefficient of Variation 39.18
|
|
Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on Terminal Phase) (Vz/F)
Glycopyrronium
|
6182 Liters (L)
Geometric Coefficient of Variation 44.59
|
5695 Liters (L)
Geometric Coefficient of Variation 43.16
|
5908 Liters (L)
Geometric Coefficient of Variation 46.44
|
|
Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on Terminal Phase) (Vz/F)
Formoterol
|
1782 Liters (L)
Geometric Coefficient of Variation 36.52
|
1734 Liters (L)
Geometric Coefficient of Variation 32.78
|
1773 Liters (L)
Geometric Coefficient of Variation 33.69
|
SECONDARY outcome
Timeframe: From Screening up to Follow-up (3 to 7 days post final dose) [approximately 55 days]Population: The safety analysis set included all participants who received at least one inhalation of any BGF MDI.
The safety and tolerability of single doses of BGF MDI HFO and BGF MDI HFA was evaluated in healthy participants.
Outcome measures
| Measure |
Treatment B (Replicate 2)
n=107 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment A
n=108 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment B (Replicate 1)
n=107 Participants
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA. The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
|---|---|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any AEs
|
9 Participants
|
16 Participants
|
21 Participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any SAE
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any SAE with outcome of death
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any AE leading to discontinuation of Investigational Product (IP)
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any possibly related AE
|
4 Participants
|
10 Participants
|
12 Participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any possibly related SAE
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Treatment A
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
Treatment B (Replicate 1)
Serious events: 0 serious events
Other events: 21 other events
Deaths: 0 deaths
Treatment B (Replicate 2)
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A
n=108 participants at risk
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment B (Replicate 1)
n=107 participants at risk
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
Treatment B (Replicate 2)
n=107 participants at risk
Participants received Test formulation in 1 of 3 possible treatment sequences: ABB, BAB, or BBA, where Treatment A: BGF MDI HFO (test), Treatment B: BGF MDI HFA (reference). The reference formulation were administered during 2 of the 3 treatment periods in order to estimate intra-subject variability.
|
|---|---|---|---|
|
Infections and infestations
Pharyngitis
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.93%
1/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Nervous system disorders
Dizziness
|
1.9%
2/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Nervous system disorders
Headache
|
3.7%
4/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
7.5%
8/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Eye disorders
Hypoaesthesia eye
|
0.93%
1/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Cardiac disorders
Palpitations
|
0.93%
1/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Vascular disorders
Flushing
|
0.93%
1/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Vascular disorders
Phlebitis
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Respiratory, thoracic and mediastinal disorders
Bradypnoea
|
0.93%
1/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.93%
1/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Respiratory, thoracic and mediastinal disorders
Dry throat
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
0.93%
1/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Respiratory, thoracic and mediastinal disorders
Upper-airway cough syndrome
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.93%
1/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Gastrointestinal disorders
Aphthous ulcer
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
1.9%
2/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Gastrointestinal disorders
Dry mouth
|
0.93%
1/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Gastrointestinal disorders
Lip dry
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Gastrointestinal disorders
Nausea
|
0.93%
1/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Gastrointestinal disorders
Salivary gland mucocoele
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.93%
1/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
1.9%
2/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.93%
1/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
General disorders
Catheter site bruise
|
1.9%
2/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
General disorders
Catheter site pain
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
1.9%
2/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
General disorders
Catheter site related reaction
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
General disorders
Catheter site swelling
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
1.9%
2/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
General disorders
Chest discomfort
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
General disorders
Injection site bruising
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
General disorders
Pyrexia
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
General disorders
Thirst
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
Injury, poisoning and procedural complications
Contusion
|
0.93%
1/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
|
General disorders
Asthenia
|
0.00%
0/108 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.93%
1/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
0.00%
0/107 • From Screening up to Follow-up Phone call (3 to 7 days post final dose) [approximately 55 days]
|
Additional Information
Global Clinical Lead
AstraZeneca Clinical Study Information Center
Phone: 1-877-240-9479
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee This confidential document is the property of AstraZeneca AB. No unpublished information contained herein may be disclosed without prior written approval from AstraZeneca AB. Access to this document must be restricted to relevant parties.
- Publication restrictions are in place
Restriction type: OTHER