Chronic Obstructive Pulmonary Disease
Conditions
Brief summary
This is a Phase I open-label, single center study to assess the PK and safety of BGF MDI 320/14.4/9.6 µg in subjects with moderate to severe COPD. Pharmacokinetics will be assessed following a single dose administration on the first treatment day (Day 1) and will be assessed again after 7 days of repeat dosing. This study includes a Screening Period of up to 28 days and a single Treatment Period of 8 days. A follow-up phone call will be conducted at least 5 days but no longer than 7 days after the last dose of study drug.
Interventions
DRUGPT010
PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol. Administered as 2 inhalations per use as instructed per the protocol.
Sponsors
Pearl Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Given their signed written informed consent to participate. * Non-child bearing potential (ie, physiologically incapable of becoming pregnant, including any female who is 2 years post-menopausal); or Child bearing potential, has a negative serum pregnancy test at Visit 1, and agrees to acceptable contraceptive methods used consistently and correctly for the duration of the study. * Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS), or other local applicable guidelines. * Current or former smokers with a history of at least 10 pack-years of cigarette smoking. * Pre-bronchodilator FEV1/FVC ratio must be \<0.70 and pre-bronchodilator FEV1 must be ≥50% and \<80% predicted normal value calculated using National Health and Nutrition Examination Survey (NHANES) III reference equations Key
Exclusion criteria
* Significant diseases or conditions to : other than COPD, active pulmonary disease such as active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung disease and uncontrolled sleep apnea . * Women who are pregnant or lactating, or are planning to become pregnant during the course of the study, or women of childbearing potential who are not using an acceptable method of contraception. * Subjects, who in the opinion of the Investigator, have a current diagnosis of asthma. * Subjects who have a history of hypersensitivity to any corticosteroid, * β2-agonist, muscarinic anticholinergic, or any component of the MDI * Alpha-1 antitrypsin deficiency as the cause of COPD
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Formoterol | Day 1 | Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Formoterol |
| Maximum Plasma Concentration (Cmax) - Formoterol | Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose) | Maximum plasma concentration (Cmax) - Formoterol |
| Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide | Day 1 | Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide |
| Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium | Day 1 | Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium |
| Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol | Day 1 | Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol |
| Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Budesonide | Day 1 | Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Budesonide |
| Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Glycopyrronium | Day 1 | Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Glycopyrronium |
| Maximum Plasma Concentration (Cmax) - Budesonide | Day 1 | Maximum plasma concentration (Cmax) - Budesonide |
| Maximum Plasma Concentration (Cmax) - Glycopyrronium | Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose) | Maximum plasma concentration (Cmax) - Glycopyrronium |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium | Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose) | Time to maximum plasma concentration (tmax) - Glycopyrronium |
| Time to Maximum Plasma Concentration (Tmax) - Formoterol | Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose) | Time to maximum plasma concentration (tmax) - Formoterol |
| Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Budesonide | Day 1 | Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Budesonide |
| Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Glycopyrronium | Day 1 | Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Glycopyrronium |
| Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Formoterol | Day 1 | Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Formoterol |
| Time to Maximum Plasma Concentration (Tmax) - Budesonide | Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose) | Time to maximum plasma concentration (tmax) - Budesonide |
Countries
United States
Participant flow
Recruitment details
This study was conducted at a single center in the United States from August 2017 to December 2017.
Pre-assignment details
BGF MDI 320/14.4/9.6 μg oral inhalation as follows: * Single-dose on the morning of Day 1 (Visit 3) followed by serial blood draws for 24 hours * BID dosing every morning and evening on Day 2 through Day 7 approximately 12 hours apart * Single-dose administration on the morning of Day 8 (Visit 5) followed by serial blood draws for 12 hours
Participants by arm
| Arm | Count |
|---|---|
| PT010 Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | PT010 |
|---|---|
| Age, Continuous | 63.7 Years STANDARD_DEVIATION 7.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 29 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 30 |
| other Total, other adverse events | 5 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide
Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide
Time frame: Day 8
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 | Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide | 3004.7 h*pg/mL | Geometric Coefficient of Variation 58.5 |
Primary
Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide
Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide
Time frame: Day 1
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 | Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide | 2407.3 h*pg/mL | Geometric Coefficient of Variation 45.4 |
Primary
Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol
Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol
Time frame: Day 8
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 | Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol | 47.4 h*pg/mL | Geometric Coefficient of Variation 30 |
Primary
Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol
Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol
Time frame: Day 1
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 | Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol | 32.6 h*pg/mL | Geometric Coefficient of Variation 30.3 |
Primary
Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium
Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium
Time frame: Day 8
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 | Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium | 73.9 h*pg/mL | Geometric Coefficient of Variation 52.9 |
Primary
Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium
Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium
Time frame: Day 1
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 | Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium | 42.5 h*pg/mL | Geometric Coefficient of Variation 45.8 |
Primary
Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Budesonide
Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Budesonide
Time frame: Day 1
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 | Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Budesonide | 2731.8 h*pg/mL | Geometric Coefficient of Variation 45.2 |
Primary
Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Formoterol
Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Formoterol
Time frame: Day 1
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 | Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Formoterol | 33.4 h*pg/mL | Geometric Coefficient of Variation 43.4 |
Primary
Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Glycopyrronium
Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Glycopyrronium
Time frame: Day 1
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 | Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Glycopyrronium | 39.4 h*pg/mL | Geometric Coefficient of Variation 73.5 |
Primary
Maximum Plasma Concentration (Cmax) - Budesonide
Maximum plasma concentration (Cmax) - Budesonide
Time frame: Day 1
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 | Maximum Plasma Concentration (Cmax) - Budesonide | 709.3 pg/mL | Geometric Coefficient of Variation 57.2 |
Primary
Maximum Plasma Concentration (Cmax) - Budesonide
Maximum plasma concentration (Cmax) - Budesonide
Time frame: Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 | Maximum Plasma Concentration (Cmax) - Budesonide | 663.2 pg/mL | Geometric Coefficient of Variation 65.8 |
Primary
Maximum Plasma Concentration (Cmax) - Formoterol
Maximum plasma concentration (Cmax) - Formoterol
Time frame: Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose)
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 | Maximum Plasma Concentration (Cmax) - Formoterol | 6.4 pg/mL | Geometric Coefficient of Variation 48.1 |
Primary
Maximum Plasma Concentration (Cmax) - Formoterol
Maximum plasma concentration (Cmax) - Formoterol
Time frame: Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 | Maximum Plasma Concentration (Cmax) - Formoterol | 7.4 pg/mL | Geometric Coefficient of Variation 38.1 |
Primary
Maximum Plasma Concentration (Cmax) - Glycopyrronium
Maximum plasma concentration (Cmax) - Glycopyrronium
Time frame: Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 | Maximum Plasma Concentration (Cmax) - Glycopyrronium | 18.3 pg/mL | Geometric Coefficient of Variation 65.4 |
Primary
Maximum Plasma Concentration (Cmax) - Glycopyrronium
Maximum plasma concentration (Cmax) - Glycopyrronium
Time frame: Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose)
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 | Maximum Plasma Concentration (Cmax) - Glycopyrronium | 17.2 pg/mL | Geometric Coefficient of Variation 80.7 |
Secondary
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Budesonide
Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Budesonide
Time frame: Day 1
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Budesonide | 2996.9 h*pg/mL | Geometric Coefficient of Variation 41 |
Secondary
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Formoterol
Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Formoterol
Time frame: Day 1
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Formoterol | 46.0 h*pg/mL | Geometric Coefficient of Variation 33.7 |
Secondary
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Glycopyrronium
Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Glycopyrronium
Time frame: Day 1
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PT010 | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Glycopyrronium | 61.2 h*pg/mL | Geometric Coefficient of Variation 85.1 |
Secondary
Time to Maximum Plasma Concentration (Tmax) - Budesonide
Time to maximum plasma concentration (tmax) - Budesonide
Time frame: Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PT010 | Time to Maximum Plasma Concentration (Tmax) - Budesonide | Day 1 | 0.33 hours |
| PT010 | Time to Maximum Plasma Concentration (Tmax) - Budesonide | Day 8 | 0.67 hours |
Secondary
Time to Maximum Plasma Concentration (Tmax) - Formoterol
Time to maximum plasma concentration (tmax) - Formoterol
Time frame: Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PT010 | Time to Maximum Plasma Concentration (Tmax) - Formoterol | Day 1 | 0.33 hours |
| PT010 | Time to Maximum Plasma Concentration (Tmax) - Formoterol | Day 8 | 0.67 hours |
Secondary
Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium
Time to maximum plasma concentration (tmax) - Glycopyrronium
Time frame: Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
Population: PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PT010 | Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium | Day 1 | 0.03 hours |
| PT010 | Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium | Day 8 | 0.10 hours |