Trial Outcomes & Findings for A Randomized, Open-label, Single-dose, Single-center, Crossover Study in Healthy Subjects to Assess the Relative Bioavailability of PT010 (NCT NCT03311373)
NCT ID: NCT03311373
Last Updated: 2020-06-11
Results Overview
Maximum plasma concentration (Cmax) per Regimen
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
56 participants
Primary outcome timeframe
Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Results posted on
2020-06-11
Participant Flow
This study was conducted at a single center in the United States from November 2017 to December 2017.
Elig subj. received single dose of BGF MDI (Budesonide, Glycopyrronium, and Formoterol Fumarate metered dose inhaler) 320/28.8/9.6 μg as: Regimen A: BGF MDI w/out spacer, w/out charcoal Regimen B: BGF MDI with spacer, w/out charcoal Regimen C: BGF MDI w/out spacer, with charcoal Regimen D: BGF MDI with spacer, with charcoal
Participant milestones
| Measure |
All Regimens
BGF MDI 320/28.8/9.6 μg
|
|---|---|
|
Overall Study
STARTED
|
56
|
|
Overall Study
COMPLETED
|
47
|
|
Overall Study
NOT COMPLETED
|
9
|
Reasons for withdrawal
| Measure |
All Regimens
BGF MDI 320/28.8/9.6 μg
|
|---|---|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Protocol Discontinuation Criteria
|
3
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Physician Decision
|
1
|
|
Overall Study
Withdrawal by Subject
|
3
|
Baseline Characteristics
A Randomized, Open-label, Single-dose, Single-center, Crossover Study in Healthy Subjects to Assess the Relative Bioavailability of PT010
Baseline characteristics by cohort
| Measure |
All Subjects
n=56 Participants
All subjects
|
|---|---|
|
Age, Continuous
|
29.9 Years
STANDARD_DEVIATION 5.3 • n=5 Participants
|
|
Sex/Gender, Customized
Male
|
34 Participants
n=5 Participants
|
|
Sex/Gender, Customized
Female
|
22 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
56 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
47 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dosePopulation: PK Population: All subjects in the Safety Population for whom at least one of the primary PK parameters for a given analyte could be calculated and who had no important protocol deviations thought to impact the analysis of the PK data.
Maximum plasma concentration (Cmax) per Regimen
Outcome measures
| Measure |
Regimen B
n=52 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and without charcoal
|
Regimen A
n=52 Participants
BGF MDI 320/28.8/9.6 μg without spacer device and without charcoal
|
Regimen C
n=52 Participants
BGF MDI 320/28.8/9.6 μg without a spacer device and with charcoal
|
Regimen D
n=52 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and with charcoal
|
|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax)-Budesonide
|
702.3 pg/mL
Geometric Coefficient of Variation 46.4
|
452.6 pg/mL
Geometric Coefficient of Variation 74.6
|
340.0 pg/mL
Geometric Coefficient of Variation 117.1
|
612.0 pg/mL
Geometric Coefficient of Variation 74.0
|
PRIMARY outcome
Timeframe: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dosePopulation: PK Population: All subjects in the Safety Population for whom at least one of the primary PK parameters for a given analyte could be calculated and who had no important protocol deviations thought to impact the analysis of the PK data.
Maximum plasma concentration (Cmax) per Regimen
Outcome measures
| Measure |
Regimen B
n=52 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and without charcoal
|
Regimen A
n=52 Participants
BGF MDI 320/28.8/9.6 μg without spacer device and without charcoal
|
Regimen C
n=51 Participants
BGF MDI 320/28.8/9.6 μg without a spacer device and with charcoal
|
Regimen D
n=51 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and with charcoal
|
|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax)-Glycopyrronium
|
47.7 pg/mL
Geometric Coefficient of Variation 73.3
|
19.0 pg/mL
Geometric Coefficient of Variation 131.0
|
17.1 pg/mL
Geometric Coefficient of Variation 181.7
|
42.1 pg/mL
Geometric Coefficient of Variation 65.4
|
PRIMARY outcome
Timeframe: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dosePopulation: PK Population: All subjects in the Safety Population for whom at least one of the primary PK parameters for a given analyte could be calculated and who had no important protocol deviations thought to impact the analysis of the PK data.
Maximum plasma concentration (Cmax) per Regimen
Outcome measures
| Measure |
Regimen B
n=52 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and without charcoal
|
Regimen A
n=52 Participants
BGF MDI 320/28.8/9.6 μg without spacer device and without charcoal
|
Regimen C
n=51 Participants
BGF MDI 320/28.8/9.6 μg without a spacer device and with charcoal
|
Regimen D
n=51 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and with charcoal
|
|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax)-Formoterol
|
18.1 pg/mL
Geometric Coefficient of Variation 58.4
|
10.8 pg/mL
Geometric Coefficient of Variation 66.3
|
8.3 pg/mL
Geometric Coefficient of Variation 98.6
|
17.9 pg/mL
Geometric Coefficient of Variation 48.1
|
PRIMARY outcome
Timeframe: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dosePopulation: PK Population: All subjects in the Safety Population for whom at least one of the primary PK parameters for a given analyte could be calculated and who had no important protocol deviations thought to impact the analysis of the PK data.
Each treatment period is equal to assigned regimen
Outcome measures
| Measure |
Regimen B
n=52 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and without charcoal
|
Regimen A
n=52 Participants
BGF MDI 320/28.8/9.6 μg without spacer device and without charcoal
|
Regimen C
n=52 Participants
BGF MDI 320/28.8/9.6 μg without a spacer device and with charcoal
|
Regimen D
n=52 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and with charcoal
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Budesonide
|
1934.0 h*pg/mL
Geometric Coefficient of Variation 54.9
|
1452.8 h*pg/mL
Geometric Coefficient of Variation 66.0
|
823.9 h*pg/mL
Geometric Coefficient of Variation 121.2
|
1618.5 h*pg/mL
Geometric Coefficient of Variation 74.9
|
PRIMARY outcome
Timeframe: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dosePopulation: PK Population: All subjects in the Safety Population for whom at least one of the primary PK parameters for a given analyte could be calculated and who had no important protocol deviations thought to impact the analysis of the PK data.
Each treatment period is equal to assigned regimen
Outcome measures
| Measure |
Regimen B
n=52 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and without charcoal
|
Regimen A
n=52 Participants
BGF MDI 320/28.8/9.6 μg without spacer device and without charcoal
|
Regimen C
n=51 Participants
BGF MDI 320/28.8/9.6 μg without a spacer device and with charcoal
|
Regimen D
n=51 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and with charcoal
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Glycopyrronium
|
74.3 h*pg/mL
Geometric Coefficient of Variation 96.4
|
48.1 h*pg/mL
Geometric Coefficient of Variation 122.4
|
19.8 h*pg/mL
Geometric Coefficient of Variation 325.0
|
69.2 h*pg/mL
Geometric Coefficient of Variation 85.2
|
PRIMARY outcome
Timeframe: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dosePopulation: PK Population: All subjects in the Safety Population for whom at least one of the primary PK parameters for a given analyte could be calculated and who had no important protocol deviations thought to impact the analysis of the PK data.
Each treatment period is equal to assigned regimen
Outcome measures
| Measure |
Regimen B
n=52 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and without charcoal
|
Regimen A
n=52 Participants
BGF MDI 320/28.8/9.6 μg without spacer device and without charcoal
|
Regimen C
n=51 Participants
BGF MDI 320/28.8/9.6 μg without a spacer device and with charcoal
|
Regimen D
n=51 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and with charcoal
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Formoterol
|
35.9 h*pg/mL
Geometric Coefficient of Variation 97.5
|
37.0 h*pg/mL
Geometric Coefficient of Variation 88.7
|
8.9 h*pg/mL
Geometric Coefficient of Variation 471.8
|
33.1 h*pg/mL
Geometric Coefficient of Variation 71.3
|
SECONDARY outcome
Timeframe: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dosePopulation: PK Population: All subjects in the Safety Population for whom at least one of the primary PK parameters for a given analyte could be calculated and who had no important protocol deviations thought to impact the analysis of the PK data.
Each treatment period is equal to assigned regimen
Outcome measures
| Measure |
Regimen B
n=52 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and without charcoal
|
Regimen A
n=52 Participants
BGF MDI 320/28.8/9.6 μg without spacer device and without charcoal
|
Regimen C
n=52 Participants
BGF MDI 320/28.8/9.6 μg without a spacer device and with charcoal
|
Regimen D
n=52 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and with charcoal
|
|---|---|---|---|---|
|
Time to Maximum Plasma Concentration (Tmax)-Budesonide
|
0.33 h (hour)
Interval 0.1 to 1.0
|
0.33 h (hour)
Interval 0.1 to 2.0
|
0.33 h (hour)
Interval 0.1 to 2.0
|
0.33 h (hour)
Interval 0.1 to 1.0
|
SECONDARY outcome
Timeframe: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dosePopulation: PK Population: All subjects in the Safety Population for whom at least one of the primary PK parameters for a given analyte could be calculated and who had no important protocol deviations thought to impact the analysis of the PK data.
Each treatment period is equal to assigned regimen
Outcome measures
| Measure |
Regimen B
n=52 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and without charcoal
|
Regimen A
n=52 Participants
BGF MDI 320/28.8/9.6 μg without spacer device and without charcoal
|
Regimen C
n=51 Participants
BGF MDI 320/28.8/9.6 μg without a spacer device and with charcoal
|
Regimen D
n=51 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and with charcoal
|
|---|---|---|---|---|
|
Time to Maximum Plasma Concentration (Tmax)-Glycopyrronium
|
0.03 h (hour)
Interval 0.03 to 0.67
|
0.03 h (hour)
Interval 0.03 to 4.0
|
0.03 h (hour)
Interval 0.03 to 0.67
|
0.03 h (hour)
Interval 0.03 to 0.1
|
SECONDARY outcome
Timeframe: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dosePopulation: PK Population: All subjects in the Safety Population for whom at least one of the primary PK parameters for a given analyte could be calculated and who had no important protocol deviations thought to impact the analysis of the PK data.
Each treatment period is equal to assigned regimen
Outcome measures
| Measure |
Regimen B
n=52 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and without charcoal
|
Regimen A
n=52 Participants
BGF MDI 320/28.8/9.6 μg without spacer device and without charcoal
|
Regimen C
n=51 Participants
BGF MDI 320/28.8/9.6 μg without a spacer device and with charcoal
|
Regimen D
n=51 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and with charcoal
|
|---|---|---|---|---|
|
Time to Maximum Plasma Concentration (Tmax)-Formoterol
|
0.10 h (hour)
Interval 0.03 to 0.67
|
0.10 h (hour)
Interval 0.03 to 4.0
|
0.10 h (hour)
Interval 0.03 to 0.67
|
0.10 h (hour)
Interval 0.03 to 0.33
|
SECONDARY outcome
Timeframe: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dosePopulation: PK Population: All subjects in the Safety Population for whom at least one of the primary PK parameters for a given analyte could be calculated and who had no important protocol deviations thought to impact the analysis of the PK data.
Each treatment period is equal to assigned regimen
Outcome measures
| Measure |
Regimen B
n=49 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and without charcoal
|
Regimen A
n=51 Participants
BGF MDI 320/28.8/9.6 μg without spacer device and without charcoal
|
Regimen C
n=49 Participants
BGF MDI 320/28.8/9.6 μg without a spacer device and with charcoal
|
Regimen D
n=48 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and with charcoal
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Budesonide
|
2132.1 h*pg/mL
Geometric Coefficient of Variation 40.9
|
1491.8 h*pg/mL
Geometric Coefficient of Variation 64.4
|
823.9 h*pg/mL
Geometric Coefficient of Variation 121.2
|
1806.2 h*pg/mL
Geometric Coefficient of Variation 39.1
|
SECONDARY outcome
Timeframe: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dosePopulation: PK Population: All subjects in the Safety Population for whom at least one of the primary PK parameters for a given analyte could be calculated and who had no important protocol deviations thought to impact the analysis of the PK data.
Each treatment period is equal to assigned regimen
Outcome measures
| Measure |
Regimen B
n=5 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and without charcoal
|
Regimen A
n=4 Participants
BGF MDI 320/28.8/9.6 μg without spacer device and without charcoal
|
Regimen C
n=7 Participants
BGF MDI 320/28.8/9.6 μg without a spacer device and with charcoal
|
Regimen D
n=7 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and with charcoal
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Glycopyrronium
|
40.4 h*pg/mL
Geometric Coefficient of Variation 49.6
|
65.9 h*pg/mL
Geometric Coefficient of Variation 44.7
|
15.2 h*pg/mL
Geometric Coefficient of Variation 54.5
|
39.2 h*pg/mL
Geometric Coefficient of Variation 96.5
|
SECONDARY outcome
Timeframe: 24 hrsPopulation: PK Population: All subjects in the Safety Population for whom at least one of the primary PK parameters for a given analyte could be calculated and who had no important protocol deviations thought to impact the analysis of the PK data.
Each treatment period is equal to assigned regimen
Outcome measures
| Measure |
Regimen B
n=20 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and without charcoal
|
Regimen A
n=18 Participants
BGF MDI 320/28.8/9.6 μg without spacer device and without charcoal
|
Regimen C
n=11 Participants
BGF MDI 320/28.8/9.6 μg without a spacer device and with charcoal
|
Regimen D
n=4 Participants
BGF MDI 320/28.8/9.6 μg with a spacer device and with charcoal
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Formoterol
|
63.2 h*pg/mL
Geometric Coefficient of Variation 37.1
|
62.7 h*pg/mL
Geometric Coefficient of Variation 62.2
|
62.6 h*pg/mL
Geometric Coefficient of Variation 55.0
|
62.0 h*pg/mL
Geometric Coefficient of Variation 42.2
|
Adverse Events
Regimen B
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Regimen A
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Regimen C
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Regimen D
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Regimen B
n=53 participants at risk
BGF MDI 320/28.8/9.6 μg with a spacer device and without charcoal
|
Regimen A
n=52 participants at risk
BGF MDI 320/28.8/9.6 μg without spacer device and without charcoal
|
Regimen C
n=52 participants at risk
BGF MDI 320/28.8/9.6 μg without a spacer device and with charcoal
|
Regimen D
n=52 participants at risk
BGF MDI 320/28.8/9.6 μg with a spacer device and with charcoal
|
|---|---|---|---|---|
|
Nervous system disorders
Dizziness
|
3.8%
2/53 • Number of events 2 • Adverse events were collected from the time of administration of the first dose of study drug to the time of the follow-up telephone call, study termination, or study exit up to a total of approximately 12 weeks.
Serious Adverse Events were collected from the time the subject signed informed consent throughout the treatment period and up to approximately 13 weeks, which includes screening and follow up (5-7 day period after study drug).
|
0.00%
0/52 • Adverse events were collected from the time of administration of the first dose of study drug to the time of the follow-up telephone call, study termination, or study exit up to a total of approximately 12 weeks.
Serious Adverse Events were collected from the time the subject signed informed consent throughout the treatment period and up to approximately 13 weeks, which includes screening and follow up (5-7 day period after study drug).
|
0.00%
0/52 • Adverse events were collected from the time of administration of the first dose of study drug to the time of the follow-up telephone call, study termination, or study exit up to a total of approximately 12 weeks.
Serious Adverse Events were collected from the time the subject signed informed consent throughout the treatment period and up to approximately 13 weeks, which includes screening and follow up (5-7 day period after study drug).
|
1.9%
1/52 • Number of events 1 • Adverse events were collected from the time of administration of the first dose of study drug to the time of the follow-up telephone call, study termination, or study exit up to a total of approximately 12 weeks.
Serious Adverse Events were collected from the time the subject signed informed consent throughout the treatment period and up to approximately 13 weeks, which includes screening and follow up (5-7 day period after study drug).
|
|
Nervous system disorders
Headache
|
5.7%
3/53 • Number of events 3 • Adverse events were collected from the time of administration of the first dose of study drug to the time of the follow-up telephone call, study termination, or study exit up to a total of approximately 12 weeks.
Serious Adverse Events were collected from the time the subject signed informed consent throughout the treatment period and up to approximately 13 weeks, which includes screening and follow up (5-7 day period after study drug).
|
1.9%
1/52 • Number of events 1 • Adverse events were collected from the time of administration of the first dose of study drug to the time of the follow-up telephone call, study termination, or study exit up to a total of approximately 12 weeks.
Serious Adverse Events were collected from the time the subject signed informed consent throughout the treatment period and up to approximately 13 weeks, which includes screening and follow up (5-7 day period after study drug).
|
3.8%
2/52 • Number of events 2 • Adverse events were collected from the time of administration of the first dose of study drug to the time of the follow-up telephone call, study termination, or study exit up to a total of approximately 12 weeks.
Serious Adverse Events were collected from the time the subject signed informed consent throughout the treatment period and up to approximately 13 weeks, which includes screening and follow up (5-7 day period after study drug).
|
3.8%
2/52 • Number of events 2 • Adverse events were collected from the time of administration of the first dose of study drug to the time of the follow-up telephone call, study termination, or study exit up to a total of approximately 12 weeks.
Serious Adverse Events were collected from the time the subject signed informed consent throughout the treatment period and up to approximately 13 weeks, which includes screening and follow up (5-7 day period after study drug).
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/53 • Adverse events were collected from the time of administration of the first dose of study drug to the time of the follow-up telephone call, study termination, or study exit up to a total of approximately 12 weeks.
Serious Adverse Events were collected from the time the subject signed informed consent throughout the treatment period and up to approximately 13 weeks, which includes screening and follow up (5-7 day period after study drug).
|
0.00%
0/52 • Adverse events were collected from the time of administration of the first dose of study drug to the time of the follow-up telephone call, study termination, or study exit up to a total of approximately 12 weeks.
Serious Adverse Events were collected from the time the subject signed informed consent throughout the treatment period and up to approximately 13 weeks, which includes screening and follow up (5-7 day period after study drug).
|
3.8%
2/52 • Number of events 2 • Adverse events were collected from the time of administration of the first dose of study drug to the time of the follow-up telephone call, study termination, or study exit up to a total of approximately 12 weeks.
Serious Adverse Events were collected from the time the subject signed informed consent throughout the treatment period and up to approximately 13 weeks, which includes screening and follow up (5-7 day period after study drug).
|
3.8%
2/52 • Number of events 2 • Adverse events were collected from the time of administration of the first dose of study drug to the time of the follow-up telephone call, study termination, or study exit up to a total of approximately 12 weeks.
Serious Adverse Events were collected from the time the subject signed informed consent throughout the treatment period and up to approximately 13 weeks, which includes screening and follow up (5-7 day period after study drug).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Drafts of any and all publications or presentations of this study must be submitted at least 30 days prior to submission for publication or presentation to Pearl Therapeutics for review, approval, and to ensure consistency. Pearl Therapeutics has the right to request appropriate modification to correct facts and to represent it's opinions, or the opinions of the publication committee, if these differ with the proposed publication.
- Publication restrictions are in place
Restriction type: OTHER