Chronic Obstructive Pulmonary Disease
Conditions
Brief summary
A study to assess the pharmacokinetics and safety of two doses of PT010 and a single dose of PT003 in healthy Chinese adult subjects
Detailed description
A Phase I, Randomized, Double-Blind, Parallel Group, Study to Assess the Pharmacokinetics and Safety of Two Doses of PT010 and a Single Dose of PT003 in Healthy Chinese Adult Subjects Following a Single Administration and After Chronic Administration for 7 Days
Interventions
DRUGPT010 (BGF MDI) 320/14.4/9.6 µg
A single dose of study drug will be administered on Day 1 and BID doses will be administered Day 2 through Day 7 of the Treatment Period, with a final single administration of study drug occurring on the morning of Day 8.
DRUGPT010 (BGF MDI) 160/14.4/9.6 µg
A single dose of study drug will be administered on Day 1 and BID doses will be administered Day 2 through Day 7 of the Treatment Period, with a final single administration of study drug occurring on the morning of Day 8.
DRUGPT003 (GFF MDI) 14.4/9.6 µg
A single dose of study drug will be administered on Day 1 and BID doses will be administered Day 2 through Day 7 of the Treatment Period, with a final single administration of study drug occurring on the morning of Day 8.
Sponsors
Pearl Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Male and female Chinese subjects 18-45 years of age * Females of childbearing potential must agree to be abstinent or else use one of the medically acceptable forms of contraception A female whose male partner has had a vasectomy must agree to use one additional form of medically acceptable contraception. A male subject with female partner of child bearing potential must agree to use one additional form of medically acceptable contraception -Be in good general health as assessed at Screening and have no clinically significant abnormal labs at Screening.
Exclusion criteria
* Pregnant or nursing female subjects or subjects who are trying to conceive * Subjects with clinically significant neurologic, cardiovascular, hepatic, renal, endocrinologic, pulmonary, hematological, psychiatric, or other medical illness that would interfere with participation in this study * Subjects with a history of ECG abnormalities * Subjects who have cancer that has not been in complete remission for at least 5 years * Male subjects with symptomatic prostatic hypertrophy that is clinically significant in the opinion of the Investigator * Male subjects with a trans-urethral resection of the prostate or full resection of the prostate within 6 months prior to Screening * Males with bladder neck obstruction or urinary retention that is clinically significant in the opinion of the Investigator * Subjects with a diagnosis of glaucoma that in the opinion of the Investigator has not been adequately treated * History of substance-related disorders within 1 year of Screening * History of smoking or the use of nicotine containing products or electronic cigarettes within 3 months of Screening by self-reporting * A positive alcohol breathalyzer or urine drug screen for drugs of abuse at the Screening Visit or at the beginning of each inpatient period * Treatment with any prescription or non-prescription drugs (including vitamins, herbal, and dietary supplements) within 30 days * Positivity for human immunodeficiency virus (HIV) or Hepatitis B surface antigen (HbsAg) or positive hepatitis C antibody at Screening * Positive for Syphilis Antibody * Subjects with any flu-like syndrome or other respiratory infections * Recently vaccinated with an attenuated live virus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Formoterol | Day 1 and Day 8 | Accumulation ratio for AUC 0-12 (RAC \[AUC 0-12\]) - Formoterol |
| Accumulation Ratio for Cmax (RAC [Cmax]) - Budesonide | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose and Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Accumulation ratio for Cmax (RAC \[Cmax\]) - Budesonide |
| Accumulation Ratio for Cmax (RAC [Cmax]) - Glycopyrronium | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose and Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Accumulation ratio for Cmax (RAC \[Cmax\]) - Glycopyrronium |
| Accumulation Ratio for Cmax (RAC [Cmax]) - Formoterol | Day 1 and Day 8 | Accumulation ratio for Cmax (RAC \[Cmax\]) - Formoterol |
| Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Budesonide | Day 1 and Day 8 | Accumulation ratio for AUC 0-12 (RAC \[AUC 0-12\]) - Budesonide |
| Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Glycopyrronium | Day 1 and Day 8 | Accumulation ratio for AUC 0-12 (RAC \[AUC 0-12\]) - Glycopyrronium |
| Apparent Total Body Clearance (CL/F) - Budesonide | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Apparent total body clearance (CL/F) - Budesonide Day 1 |
| Maximum Plasma Concentration (Cmax) - Budesonide | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Maximum plasma concentration (Cmax) of Budesonide Day 1 |
| Maximum Plasma Concentration (Cmax) - Glycopyrronium | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Maximum plasma concentration (Cmax) of Glycopyrronium Day 1 |
| Maximum Plasma Concentration (Cmax) - Formoterol | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Maximum plasma concentration (Cmax) of Formoterol Day 1 |
| Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Budesonide | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Budesonide Day 1 |
| Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Glycopyrronium | Day 1 | Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Glycopyrronium Day 1 |
| Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Formoterol | Day 1 | Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Formoterol Day 1 |
| Time to Maximum Plasma Concentration (Tmax) - Budesonide | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Time to maximum plasma concentration (tmax) - Budesonide Day 1 |
| Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Time to maximum plasma concentration (tmax) - Glycopyrronium Day 1 |
| Time to Maximum Plasma Concentration (Tmax) - Formoterol | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Time to maximum plasma concentration (tmax) - Formoterol Day 1 |
| Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Budesonide | Day 1 | Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-t) - Budesonide Day 1 |
| Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Glycopyrronium | Day 1 | Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-t) - Glycopyrronium Day 1 |
| Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Formoterol | Day 1 | Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-t) - Formoterol Day 1 |
| Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Budesonide | Day 1 | Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC 0-∞) - Budesonide Day 1 |
| Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Glycopyrronium | Day 1 | Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC 0-∞) - Glycopyrronium Day 1 |
| Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Formoterol | Day 1 | Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC 0-∞) - Formoterol Day 1 |
| Elimination Half-life (t½) - Budesonide | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Elimination half-life (t½) - Budesonide Day 1 |
| Elimination Half-life (t½) - Glycopyrronium | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Elimination half-life (t½) - Glycopyrronium Day 1 |
| Elimination Half-life (t½) - Formoterol | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Elimination half-life (t½) - Formoterol Day 1 |
| Apparent Total Body Clearance (CL/F) - Glycopyrronium | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Apparent total body clearance (CL/F) - Glycopyrronium Day 1 |
| Apparent Total Body Clearance (CL/F) - Formoterol | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Apparent total body clearance (CL/F) - Formoterol Day 1 |
| Apparent Volume of Distribution (Vd/F) - Budesonide | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Apparent volume of distribution (Vd/F) - Budesonide - Day 1 |
| Apparent Volume of Distribution (Vd/F) - Glycopyrronium | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Apparent volume of distribution (Vd/F) - Glycopyrronium - Day 1 |
| Apparent Volume of Distribution (Vd/F) - Formoterol | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Apparent volume of distribution (Vd/F) - Formoterol - Day 1 |
| Terminal Elimination Rate Constant (λz) - Budesonide | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Terminal elimination rate constant (λz) - Budesonide - Day 1 |
| Terminal Elimination Rate Constant (λz) - Glycopyrronium | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Terminal elimination rate constant (λz) - Glycopyrronium - Day 1 |
| Terminal Elimination Rate Constant (λz) - Formoterol | Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose | Terminal elimination rate constant (λz) - Formoterol - Day 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Laboratory Tests | Visit 4, Day 8 | Number of subjects with clinically significant changes in post baseline laboratory tests |
| Vital Signs | Visit 4, Day 8 | Number of subjects with clinically significant changes in post baseline vital signs |
| Electrocardiogram | Visit 4, Day 8 | Number of subjects with clinically significant changes in post baseline electrocardiogram |
| Serious Adverse Events/Adverse Events | Visit 4, Day 8 | Number of subjects with clinically significant changes in post baseline serious TEAEs (treatment-emergent adverse events) or TEAEs leading to withdrawal |
| Physical Exam Findings | Visit 4, Day 8 | Number of subjects with clinically significant changes in post baseline physical exam findings |
Countries
China
Participant flow
Recruitment details
This study was conducted at a single site in China.
Pre-assignment details
Subjects were randomized in a 1:1:1 ratio to 1 of 3 treatments: BGF MDI 320/14.4/9.6 μg, BGF MDI 160/14.4/9.6 μg, or GFF MDI 14.4/9.6 μg.
Participants by arm
| Arm | Count |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg PT010 Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg | 32 |
| PT010 (BGF MDI) 320/14.4/9.6 µg PT010 Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg | 32 |
| PT010 (BGF MDI) 160/14.4/9.6 µg PT010 Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 160/14.4/9.6 µg | 32 |
| PT010 (BGF MDI) 160/14.4/9.6 µg PT010 Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 160/14.4/9.6 µg | 32 |
| PT003 (GFF MDI) 14.4/9.6 µg PT003 Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI) 14.4/9.6 µg | 32 |
| PT003 (GFF MDI) 14.4/9.6 µg PT003 Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI) 14.4/9.6 µg | 32 |
| Total | 192 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | PT010 (BGF MDI) 320/14.4/9.6 µg | PT010 (BGF MDI) 160/14.4/9.6 µg | PT003 (GFF MDI) 14.4/9.6 µg | Total |
|---|---|---|---|---|
| Age, Continuous | 25.1 Years STANDARD_DEVIATION 3.8 | 26.9 Years STANDARD_DEVIATION 5.1 | 24.7 Years STANDARD_DEVIATION 4.1 | 25.6 Years STANDARD_DEVIATION 4.4 |
| BMI | 21.5 kg/m^2 STANDARD_DEVIATION 1.4 | 21.6 kg/m^2 STANDARD_DEVIATION 1.2 | 21.9 kg/m^2 STANDARD_DEVIATION 1.1 | 21.7 kg/m^2 STANDARD_DEVIATION 1.2 |
| Race/Ethnicity, Customized Chinese subjects | 32 Participants | 32 Participants | 32 Participants | 96 Participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 3 Participants | 16 Participants |
| Sex: Female, Male Male | 25 Participants | 26 Participants | 29 Participants | 80 Participants |
| Smoking Status Former Smoker | 4 Participants | 3 Participants | 2 Participants | 9 Participants |
| Smoking Status Non Smoker | 28 Participants | 29 Participants | 30 Participants | 87 Participants |
| Weight | 59.99 kg STANDARD_DEVIATION 5.29 | 60.00 kg STANDARD_DEVIATION 6.13 | 62.75 kg STANDARD_DEVIATION 5.31 | 60.91 kg STANDARD_DEVIATION 5.68 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 14 / 32 | 11 / 32 | 14 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 | 0 / 32 |
Outcome results
Primary
Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Budesonide
Accumulation ratio for AUC 0-12 (RAC \[AUC 0-12\]) - Budesonide
Time frame: Day 1 and Day 8
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Budesonide | 1.455 Ratio | Geometric Coefficient of Variation 45.9 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Budesonide | 1.539 Ratio | Geometric Coefficient of Variation 37.1 |
Primary
Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Formoterol
Accumulation ratio for AUC 0-12 (RAC \[AUC 0-12\]) - Formoterol
Time frame: Day 1 and Day 8
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Formoterol | 1.718 Ratio | Geometric Coefficient of Variation 28.7 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Formoterol | 1.835 Ratio | Geometric Coefficient of Variation 26.2 |
| PT003 (GFF MDI) 14.4/9.6 µg | Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Formoterol | 1.620 Ratio | Geometric Coefficient of Variation 27.5 |
Primary
Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Glycopyrronium
Accumulation ratio for AUC 0-12 (RAC \[AUC 0-12\]) - Glycopyrronium
Time frame: Day 1 and Day 8
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Glycopyrronium | 3.324 Ratio | Geometric Coefficient of Variation 47.5 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Glycopyrronium | 3.030 Ratio | Geometric Coefficient of Variation 43 |
| PT003 (GFF MDI) 14.4/9.6 µg | Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Glycopyrronium | 3.189 Ratio | Geometric Coefficient of Variation 31.5 |
Primary
Accumulation Ratio for Cmax (RAC [Cmax]) - Budesonide
Accumulation ratio for Cmax (RAC \[Cmax\]) - Budesonide
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose and Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Accumulation Ratio for Cmax (RAC [Cmax]) - Budesonide | 1.400 Ratio | Geometric Coefficient of Variation 71.4 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Accumulation Ratio for Cmax (RAC [Cmax]) - Budesonide | 1.406 Ratio | Geometric Coefficient of Variation 62.6 |
Primary
Accumulation Ratio for Cmax (RAC [Cmax]) - Formoterol
Accumulation ratio for Cmax (RAC \[Cmax\]) - Formoterol
Time frame: Day 1 and Day 8
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Accumulation Ratio for Cmax (RAC [Cmax]) - Formoterol | 1.678 Ratio | Geometric Coefficient of Variation 50.1 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Accumulation Ratio for Cmax (RAC [Cmax]) - Formoterol | 1.706 Ratio | Geometric Coefficient of Variation 42.1 |
| PT003 (GFF MDI) 14.4/9.6 µg | Accumulation Ratio for Cmax (RAC [Cmax]) - Formoterol | 1.668 Ratio | Geometric Coefficient of Variation 62.2 |
Primary
Accumulation Ratio for Cmax (RAC [Cmax]) - Glycopyrronium
Accumulation ratio for Cmax (RAC \[Cmax\]) - Glycopyrronium
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose and Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Accumulation Ratio for Cmax (RAC [Cmax]) - Glycopyrronium | 2.383 Ratio | Geometric Coefficient of Variation 86.4 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Accumulation Ratio for Cmax (RAC [Cmax]) - Glycopyrronium | 2.319 Ratio | Geometric Coefficient of Variation 90.3 |
| PT003 (GFF MDI) 14.4/9.6 µg | Accumulation Ratio for Cmax (RAC [Cmax]) - Glycopyrronium | 2.412 Ratio | Geometric Coefficient of Variation 89.7 |
Primary
Apparent Total Body Clearance (CL/F) - Budesonide
Apparent total body clearance (CL/F) - Budesonide Day 1
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Apparent Total Body Clearance (CL/F) - Budesonide | 165.271 L/h | Geometric Coefficient of Variation 42 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Apparent Total Body Clearance (CL/F) - Budesonide | 182.508 L/h | Geometric Coefficient of Variation 58.8 |
Primary
Apparent Total Body Clearance (CL/F) - Formoterol
Apparent total body clearance (CL/F) - Formoterol Day 1
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Apparent Total Body Clearance (CL/F) - Formoterol | 155.801 L/h | Geometric Coefficient of Variation 37.5 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Apparent Total Body Clearance (CL/F) - Formoterol | 131.286 L/h | Geometric Coefficient of Variation 40.5 |
| PT003 (GFF MDI) 14.4/9.6 µg | Apparent Total Body Clearance (CL/F) - Formoterol | 135.962 L/h | Geometric Coefficient of Variation 46 |
Primary
Apparent Total Body Clearance (CL/F) - Glycopyrronium
Apparent total body clearance (CL/F) - Glycopyrronium Day 1
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Apparent Total Body Clearance (CL/F) - Glycopyrronium | 406.038 L/h | Geometric Coefficient of Variation 19.6 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Apparent Total Body Clearance (CL/F) - Glycopyrronium | 436.184 L/h | — |
| PT003 (GFF MDI) 14.4/9.6 µg | Apparent Total Body Clearance (CL/F) - Glycopyrronium | 330.757 L/h | Geometric Coefficient of Variation 18.3 |
Primary
Apparent Volume of Distribution (Vd/F) - Budesonide
Apparent volume of distribution (Vd/F) - Budesonide - Day 1
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Apparent Volume of Distribution (Vd/F) - Budesonide | 1090.237 L | Geometric Coefficient of Variation 43 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Apparent Volume of Distribution (Vd/F) - Budesonide | 834.269 L | Geometric Coefficient of Variation 56.2 |
Primary
Apparent Volume of Distribution (Vd/F) - Formoterol
Apparent volume of distribution (Vd/F) - Formoterol - Day 1
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Apparent Volume of Distribution (Vd/F) - Formoterol | 1125.215 L | Geometric Coefficient of Variation 26 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Apparent Volume of Distribution (Vd/F) - Formoterol | 1000.172 L | Geometric Coefficient of Variation 29.2 |
| PT003 (GFF MDI) 14.4/9.6 µg | Apparent Volume of Distribution (Vd/F) - Formoterol | 1035.257 L | Geometric Coefficient of Variation 30.9 |
Primary
Apparent Volume of Distribution (Vd/F) - Glycopyrronium
Apparent volume of distribution (Vd/F) - Glycopyrronium - Day 1
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Apparent Volume of Distribution (Vd/F) - Glycopyrronium | 2172.038 L | Geometric Coefficient of Variation 17.6 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Apparent Volume of Distribution (Vd/F) - Glycopyrronium | 2123.999 L | — |
| PT003 (GFF MDI) 14.4/9.6 µg | Apparent Volume of Distribution (Vd/F) - Glycopyrronium | 1864.314 L | Geometric Coefficient of Variation 49.8 |
Primary
Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Budesonide
Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Budesonide Day 1
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Budesonide | 1747.910 h*pg/mL | Geometric Coefficient of Variation 43.5 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Budesonide | 811.812 h*pg/mL | Geometric Coefficient of Variation 58.2 |
Primary
Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Budesonide
Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Budesonide Day 8
Time frame: Day 8
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Budesonide | 2509.888 h*pg/mL | Geometric Coefficient of Variation 53.4 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Budesonide | 1249.615 h*pg/mL | Geometric Coefficient of Variation 52 |
Primary
Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Formoterol
Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Formoterol Day 1
Time frame: Day 1
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Formoterol | 47.843 h*pg/mL | Geometric Coefficient of Variation 35 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Formoterol | 46.492 h*pg/mL | Geometric Coefficient of Variation 39.3 |
| PT003 (GFF MDI) 14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Formoterol | 53.583 h*pg/mL | Geometric Coefficient of Variation 38 |
Primary
Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Formoterol
Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Formoterol Day 8
Time frame: Day 8
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Formoterol | 81.936 h*pg/mL | Geometric Coefficient of Variation 39.5 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Formoterol | 85.322 h*pg/mL | Geometric Coefficient of Variation 34 |
| PT003 (GFF MDI) 14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Formoterol | 83.499 h*pg/mL | Geometric Coefficient of Variation 37.8 |
Primary
Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Glycopyrronium
Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Glycopyrronium Day 8
Time frame: Day 8
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Glycopyrronium | 69.487 h*pg/mL | Geometric Coefficient of Variation 64.8 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Glycopyrronium | 77.078 h*pg/mL | Geometric Coefficient of Variation 47.5 |
| PT003 (GFF MDI) 14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Glycopyrronium | 72.636 h*pg/mL | Geometric Coefficient of Variation 57.2 |
Primary
Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Glycopyrronium
Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Glycopyrronium Day 1
Time frame: Day 1
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Glycopyrronium | 29.400 h*pg/mL | Geometric Coefficient of Variation 23.5 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Glycopyrronium | 27.197 h*pg/mL | Geometric Coefficient of Variation 41.3 |
| PT003 (GFF MDI) 14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Glycopyrronium | 29.002 h*pg/mL | Geometric Coefficient of Variation 42.6 |
Primary
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Budesonide
Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC 0-∞) - Budesonide Day 1
Time frame: Day 1
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Budesonide | 1936.211 h*pg/mL | Geometric Coefficient of Variation 42 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Budesonide | 876.673 h*pg/mL | Geometric Coefficient of Variation 58.8 |
Primary
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Formoterol
Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC 0-∞) - Formoterol Day 1
Time frame: Day 1
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Formoterol | 61.617 h*pg/mL | Geometric Coefficient of Variation 37.5 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Formoterol | 73.123 h*pg/mL | Geometric Coefficient of Variation 40.5 |
| PT003 (GFF MDI) 14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Formoterol | 70.608 h*pg/mL | Geometric Coefficient of Variation 46 |
Primary
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Glycopyrronium
Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC 0-∞) - Glycopyrronium Day 1
Time frame: Day 1
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Glycopyrronium | 35.465 h*pg/mL | Geometric Coefficient of Variation 19.6 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Glycopyrronium | 33.014 h*pg/mL | — |
| PT003 (GFF MDI) 14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Glycopyrronium | 43.537 h*pg/mL | Geometric Coefficient of Variation 18.3 |
Primary
Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Budesonide
Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-t) - Budesonide Day 1
Time frame: Day 1
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Budesonide | 1884.912 h*pg/mL | Geometric Coefficient of Variation 43.5 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Budesonide | 830.012 h*pg/mL | Geometric Coefficient of Variation 61.1 |
Primary
Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Formoterol
Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-t) - Formoterol Day 1
Time frame: Day 1
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Formoterol | 48.326 h*pg/mL | Geometric Coefficient of Variation 41.4 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Formoterol | 47.408 h*pg/mL | Geometric Coefficient of Variation 48.2 |
| PT003 (GFF MDI) 14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Formoterol | 45.950 h*pg/mL | Geometric Coefficient of Variation 78.1 |
Primary
Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Glycopyrronium
Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-t) - Glycopyrronium Day 1
Time frame: Day 1
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Glycopyrronium | 17.616 h*pg/mL | Geometric Coefficient of Variation 89.8 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Glycopyrronium | 17.707 h*pg/mL | Geometric Coefficient of Variation 111.2 |
| PT003 (GFF MDI) 14.4/9.6 µg | Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Glycopyrronium | 20.287 h*pg/mL | Geometric Coefficient of Variation 103.3 |
Primary
Elimination Half-life (t½) - Budesonide
Elimination half-life (t½) - Budesonide Day 1
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Elimination Half-life (t½) - Budesonide | 4.572 h | Geometric Coefficient of Variation 25.3 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Elimination Half-life (t½) - Budesonide | 3.168 h | Geometric Coefficient of Variation 31.9 |
Primary
Elimination Half-life (t½) - Formoterol
Elimination half-life (t½) - Formoterol Day 1
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Elimination Half-life (t½) - Formoterol | 5.098 h | Geometric Coefficient of Variation 22.7 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Elimination Half-life (t½) - Formoterol | 5.657 h | Geometric Coefficient of Variation 38.1 |
| PT003 (GFF MDI) 14.4/9.6 µg | Elimination Half-life (t½) - Formoterol | 5.628 h | Geometric Coefficient of Variation 34.2 |
Primary
Elimination Half-life (t½) - Glycopyrronium
Elimination half-life (t½) - Glycopyrronium Day 1
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Elimination Half-life (t½) - Glycopyrronium | 5.676 h | Geometric Coefficient of Variation 52.5 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Elimination Half-life (t½) - Glycopyrronium | 8.539 h | Geometric Coefficient of Variation 161.3 |
| PT003 (GFF MDI) 14.4/9.6 µg | Elimination Half-life (t½) - Glycopyrronium | 6.194 h | Geometric Coefficient of Variation 108.2 |
Primary
Maximum Plasma Concentration (Cmax) - Budesonide
Maximum plasma concentration (Cmax) of Budesonide Day 8
Time frame: Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Maximum Plasma Concentration (Cmax) - Budesonide | 626.435 pg/mL | Geometric Coefficient of Variation 78.1 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Maximum Plasma Concentration (Cmax) - Budesonide | 315.425 pg/mL | Geometric Coefficient of Variation 80.2 |
Primary
Maximum Plasma Concentration (Cmax) - Budesonide
Maximum plasma concentration (Cmax) of Budesonide Day 1
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Maximum Plasma Concentration (Cmax) - Budesonide | 459.308 pg/mL | Geometric Coefficient of Variation 67.6 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Maximum Plasma Concentration (Cmax) - Budesonide | 224.298 pg/mL | Geometric Coefficient of Variation 98.1 |
Primary
Maximum Plasma Concentration (Cmax) - Formoterol
Maximum plasma concentration (Cmax) of Formoterol Day 1
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Maximum Plasma Concentration (Cmax) - Formoterol | 9.651 pg/mL | Geometric Coefficient of Variation 55.8 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Maximum Plasma Concentration (Cmax) - Formoterol | 9.932 pg/mL | Geometric Coefficient of Variation 71.9 |
| PT003 (GFF MDI) 14.4/9.6 µg | Maximum Plasma Concentration (Cmax) - Formoterol | 10.618 pg/mL | Geometric Coefficient of Variation 76.6 |
Primary
Maximum Plasma Concentration (Cmax) - Formoterol
Maximum plasma concentration (Cmax) of Formoterol Day 8
Time frame: Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Maximum Plasma Concentration (Cmax) - Formoterol | 16.125 pg/mL | Geometric Coefficient of Variation 59.1 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Maximum Plasma Concentration (Cmax) - Formoterol | 16.945 pg/mL | Geometric Coefficient of Variation 54.5 |
| PT003 (GFF MDI) 14.4/9.6 µg | Maximum Plasma Concentration (Cmax) - Formoterol | 17.710 pg/mL | Geometric Coefficient of Variation 57.6 |
Primary
Maximum Plasma Concentration (Cmax) - Glycopyrronium
Maximum plasma concentration (Cmax) of Glycopyrronium Day 1
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Maximum Plasma Concentration (Cmax) - Glycopyrronium | 4.884 pg/mL | Geometric Coefficient of Variation 92.5 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Maximum Plasma Concentration (Cmax) - Glycopyrronium | 5.286 pg/mL | Geometric Coefficient of Variation 120.8 |
| PT003 (GFF MDI) 14.4/9.6 µg | Maximum Plasma Concentration (Cmax) - Glycopyrronium | 5.674 pg/mL | Geometric Coefficient of Variation 113.4 |
Primary
Maximum Plasma Concentration (Cmax) - Glycopyrronium
Maximum plasma concentration (Cmax) of Glycopyrronium Day 8
Time frame: Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Maximum Plasma Concentration (Cmax) - Glycopyrronium | 11.303 pg/mL | Geometric Coefficient of Variation 96.9 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Maximum Plasma Concentration (Cmax) - Glycopyrronium | 11.754 pg/mL | Geometric Coefficient of Variation 103 |
| PT003 (GFF MDI) 14.4/9.6 µg | Maximum Plasma Concentration (Cmax) - Glycopyrronium | 13.124 pg/mL | Geometric Coefficient of Variation 82.3 |
Primary
Terminal Elimination Rate Constant (λz) - Budesonide
Terminal elimination rate constant (λz) - Budesonide - Day 1
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Terminal Elimination Rate Constant (λz) - Budesonide | 0.152 1/h | Geometric Coefficient of Variation 25.3 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Terminal Elimination Rate Constant (λz) - Budesonide | 0.219 1/h | Geometric Coefficient of Variation 31.9 |
Primary
Terminal Elimination Rate Constant (λz) - Formoterol
Terminal elimination rate constant (λz) - Formoterol - Day 1
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Terminal Elimination Rate Constant (λz) - Formoterol | 0.136 1/h | Geometric Coefficient of Variation 22.7 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Terminal Elimination Rate Constant (λz) - Formoterol | 0.123 1/h | Geometric Coefficient of Variation 38.1 |
| PT003 (GFF MDI) 14.4/9.6 µg | Terminal Elimination Rate Constant (λz) - Formoterol | 0.123 1/h | Geometric Coefficient of Variation 34.2 |
Primary
Terminal Elimination Rate Constant (λz) - Glycopyrronium
Terminal elimination rate constant (λz) - Glycopyrronium - Day 1
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Terminal Elimination Rate Constant (λz) - Glycopyrronium | 0.122 1/h | Geometric Coefficient of Variation 52.5 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Terminal Elimination Rate Constant (λz) - Glycopyrronium | 0.081 1/h | Geometric Coefficient of Variation 161.3 |
| PT003 (GFF MDI) 14.4/9.6 µg | Terminal Elimination Rate Constant (λz) - Glycopyrronium | 0.112 1/h | Geometric Coefficient of Variation 108.2 |
Primary
Time to Maximum Plasma Concentration (Tmax) - Budesonide
Time to maximum plasma concentration (tmax) - Budesonide Day 1
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Time to Maximum Plasma Concentration (Tmax) - Budesonide | 0.333 h |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Time to Maximum Plasma Concentration (Tmax) - Budesonide | 0.333 h |
Primary
Time to Maximum Plasma Concentration (Tmax) - Budesonide
Time to maximum plasma concentration (tmax) - Budesonide Day 8
Time frame: Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Time to Maximum Plasma Concentration (Tmax) - Budesonide | 0.333 h |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Time to Maximum Plasma Concentration (Tmax) - Budesonide | 0.333 h |
Primary
Time to Maximum Plasma Concentration (Tmax) - Formoterol
Time to maximum plasma concentration (tmax) - Formoterol Day 1
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Time to Maximum Plasma Concentration (Tmax) - Formoterol | 0.833 h |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Time to Maximum Plasma Concentration (Tmax) - Formoterol | 0.100 h |
| PT003 (GFF MDI) 14.4/9.6 µg | Time to Maximum Plasma Concentration (Tmax) - Formoterol | 0.100 h |
Primary
Time to Maximum Plasma Concentration (Tmax) - Formoterol
Time to maximum plasma concentration (tmax) - Formoterol Day 8
Time frame: Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Time to Maximum Plasma Concentration (Tmax) - Formoterol | 0.100 h |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Time to Maximum Plasma Concentration (Tmax) - Formoterol | 0.100 h |
| PT003 (GFF MDI) 14.4/9.6 µg | Time to Maximum Plasma Concentration (Tmax) - Formoterol | 0.100 h |
Primary
Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium
Time to maximum plasma concentration (tmax) - Glycopyrronium Day 1
Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium | 0.100 h |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium | 0.100 h |
| PT003 (GFF MDI) 14.4/9.6 µg | Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium | 0.100 h |
Primary
Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium
Time to maximum plasma concentration (tmax) - Glycopyrronium Day 8
Time frame: Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Population: PK Population - defined as all subjects in the Safety Population who had sufficient data to reliably calculate at least 1 PK parameter and did not have a major protocol deviation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium | 0.333 h |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium | 0.333 h |
| PT003 (GFF MDI) 14.4/9.6 µg | Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium | 0.333 h |
Secondary
Electrocardiogram
Number of subjects with clinically significant changes in post baseline electrocardiogram
Time frame: Visit 4, Day 8
Population: Safety Population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Electrocardiogram | Significant electrocardiogram changes | 0 Participants |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Electrocardiogram | Significant electrocardiogram changes | 0 Participants |
| PT003 (GFF MDI) 14.4/9.6 µg | Electrocardiogram | Significant electrocardiogram changes | 0 Participants |
Secondary
Laboratory Tests
Number of subjects with clinically significant changes in post baseline laboratory tests
Time frame: Visit 4, Day 8
Population: Safety Population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Laboratory Tests | Potassium | 0 Participants |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Laboratory Tests | Potassium | 1 Participants |
| PT003 (GFF MDI) 14.4/9.6 µg | Laboratory Tests | Potassium | 0 Participants |
Secondary
Physical Exam Findings
Number of subjects with clinically significant changes in post baseline physical exam findings
Time frame: Visit 4, Day 8
Population: Safety Population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Physical Exam Findings | Significant Findings | 0 Participants |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Physical Exam Findings | Significant Findings | 0 Participants |
| PT003 (GFF MDI) 14.4/9.6 µg | Physical Exam Findings | Significant Findings | 0 Participants |
Secondary
Serious Adverse Events/Adverse Events
Number of subjects with clinically significant changes in post baseline serious TEAEs (treatment-emergent adverse events) or TEAEs leading to withdrawal
Time frame: Visit 4, Day 8
Population: Safety Population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Serious Adverse Events/Adverse Events | Serious TEAEs/TEAEs leading to withdrawal | 0 Participants |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Serious Adverse Events/Adverse Events | Serious TEAEs/TEAEs leading to withdrawal | 0 Participants |
| PT003 (GFF MDI) 14.4/9.6 µg | Serious Adverse Events/Adverse Events | Serious TEAEs/TEAEs leading to withdrawal | 0 Participants |
Secondary
Vital Signs
Number of subjects with clinically significant changes in post baseline vital signs
Time frame: Visit 4, Day 8
Population: Safety Population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | Vital Signs | Bradycardia events | 2 Participants |
| PT010 (BGF MDI) 160/14.4/9.6 µg | Vital Signs | Bradycardia events | 0 Participants |
| PT003 (GFF MDI) 14.4/9.6 µg | Vital Signs | Bradycardia events | 0 Participants |