Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD
Brief summary
Randomized, Open-label, Single-dose, Single-center, Crossover Study in Healthy Subjects to Assess the Relative Bioavailability of PT010
Detailed description
A Randomized, Open-label, Single-dose, Single-center, Crossover Study in Healthy Subjects to Assess the Relative Bioavailability of PT010 Administered With and Without a Spacer, and With and Without Oral Charcoal
Interventions
DRUGRegimen C
2 inhalations BGF MDI; no spacer device; with oral charcoal - reference formulation/lung exposure
DRUGRegimen D
2 inhalations BGF MDI; AeroChamber Plus Flow-Vu spacer device; with oral charcoal - test formulation/lung exposure
DRUGRegimen A
2 inhalations BGF MDI; no spacer device; no oral charcoal - reference formulation/total systemic exposure
DRUGRegimen B
2 inhalations BGF MDI; AeroChamber Plus Flow-Vu spacer device; no oral charcoal - test formulation/total systemic exposure
Sponsors
Pearl Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Signed and dated Independent Ethics Committee (IEC)/Institutional Review Board (IRB)-approved Informed Consent Form (ICF) before any protocol-specific screening procedures are performed * Male and female subjects 18 to 40 years of age, inclusive * Be in good general health as determined by a thorough medical history and physical examination, ECG, vital signs, and clinical laboratory evaluation * Non-childbearing potential (ie, physiologically incapable of becoming pregnant, including any female who is 2 years post-menopausal, or surgically sterile * Male subjects who are sexually active must agree to use a double-barrier method of contraception (condom with spermicide) from the first dose of randomized study drug until 2 weeks after their last dose, and must not donate sperm during their study participation period * Screening laboratory tests must be within normal range or determined to not be clinically significant by the Investigator. * Demonstrate correct MDI administration technique Key
Exclusion criteria
* For female subjects, a positive serum human chorionic gonadotropin (hCG) test at screening or a positive urine hCG at admission for any of the 4 Treatment Periods * 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 who have cancer that has not been in complete remission for at least 5 years * Male subjects with a trans-urethral resection of the prostate or full resection of the prostate within 6 months prior to screening * Subjects with bladder neck obstruction or urinary retention that is clinically significant in the opinion of the Investigator * History of substance-related disorders (with the exception of caffeine-related and nicotine-related disorders) within 1 year of screening * History of smoking or the use of nicotine-containing products within 3 months of screening by self-reporting * A positive alcohol breathalyzer or urine drug screen for drugs of abuse at screening or at the beginning of each Treatment Period * Treatment with any prescription or non-prescription drugs including vitamins, herbal, and dietary supplements for 28 days or 5 half-lives, whichever is longer, before study drug use * Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to the beginning of the screening Period * Subjects with any flu-like syndrome or other respiratory infections within 2 weeks of drug administration or who have been vaccinated with an attenuated live virus within 4 weeks of drug administration * Any other condition and/or situation that causes the Investigator to deem a subject unsuitable for the study (eg, inability to medically tolerate the study procedures, or a subject's unwillingness to comply with study-related procedures)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Formoterol | Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose | Each treatment period is equal to assigned regimen |
| Maximum Plasma Concentration (Cmax)-Budesonide | Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose | Maximum plasma concentration (Cmax) per Regimen |
| Maximum Plasma Concentration (Cmax)-Glycopyrronium | Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose | Maximum plasma concentration (Cmax) per Regimen |
| Maximum Plasma Concentration (Cmax)-Formoterol | Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose | Maximum plasma concentration (Cmax) per Regimen |
| Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Budesonide | Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose | Each treatment period is equal to assigned regimen |
| Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Glycopyrronium | Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose | Each treatment period is equal to assigned regimen |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Plasma Concentration (Tmax)-Budesonide | Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose | Each treatment period is equal to assigned regimen |
| Time to Maximum Plasma Concentration (Tmax)-Glycopyrronium | Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose | Each treatment period is equal to assigned regimen |
| Time to Maximum Plasma Concentration (Tmax)-Formoterol | Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose | Each treatment period is equal to assigned regimen |
| Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Budesonide | Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose | Each treatment period is equal to assigned regimen |
| Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Glycopyrronium | Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose | Each treatment period is equal to assigned regimen |
| Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Formoterol | 24 hrs | Each treatment period is equal to assigned regimen |
Countries
United States
Participant flow
Recruitment details
This study was conducted at a single center in the United States from November 2017 to December 2017.
Pre-assignment details
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
Participants by arm
| Arm | Count |
|---|---|
| All Subjects All subjects | 56 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Protocol Discontinuation Criteria | 3 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Continuous | 29.9 Years STANDARD_DEVIATION 5.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 47 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 | 1 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Sex/Gender, Customized Female | 22 Participants |
| Sex/Gender, Customized Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 52 | 0 / 52 | 0 / 52 |
| other Total, other adverse events | 4 / 53 | 1 / 52 | 4 / 52 | 4 / 52 |
| serious Total, serious adverse events | 0 / 53 | 0 / 52 | 0 / 52 | 0 / 52 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Budesonide
Each treatment period is equal to assigned regimen
Time frame: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Regimen B | 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 |
| Regimen A | Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Budesonide | 1452.8 h*pg/mL | Geometric Coefficient of Variation 66 |
| Regimen C | Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Budesonide | 823.9 h*pg/mL | Geometric Coefficient of Variation 121.2 |
| Regimen D | Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Budesonide | 1618.5 h*pg/mL | Geometric Coefficient of Variation 74.9 |
Primary
Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Formoterol
Each treatment period is equal to assigned regimen
Time frame: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Regimen B | 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 |
| Regimen A | Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Formoterol | 37.0 h*pg/mL | Geometric Coefficient of Variation 88.7 |
| Regimen C | Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Formoterol | 8.9 h*pg/mL | Geometric Coefficient of Variation 471.8 |
| Regimen D | Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Formoterol | 33.1 h*pg/mL | Geometric Coefficient of Variation 71.3 |
Primary
Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Glycopyrronium
Each treatment period is equal to assigned regimen
Time frame: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Regimen B | 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 |
| Regimen A | Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Glycopyrronium | 48.1 h*pg/mL | Geometric Coefficient of Variation 122.4 |
| Regimen C | Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Glycopyrronium | 19.8 h*pg/mL | Geometric Coefficient of Variation 325 |
| Regimen D | Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Glycopyrronium | 69.2 h*pg/mL | Geometric Coefficient of Variation 85.2 |
Primary
Maximum Plasma Concentration (Cmax)-Budesonide
Maximum plasma concentration (Cmax) per Regimen
Time frame: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Regimen B | Maximum Plasma Concentration (Cmax)-Budesonide | 702.3 pg/mL | Geometric Coefficient of Variation 46.4 |
| Regimen A | Maximum Plasma Concentration (Cmax)-Budesonide | 452.6 pg/mL | Geometric Coefficient of Variation 74.6 |
| Regimen C | Maximum Plasma Concentration (Cmax)-Budesonide | 340.0 pg/mL | Geometric Coefficient of Variation 117.1 |
| Regimen D | Maximum Plasma Concentration (Cmax)-Budesonide | 612.0 pg/mL | Geometric Coefficient of Variation 74 |
Primary
Maximum Plasma Concentration (Cmax)-Formoterol
Maximum plasma concentration (Cmax) per Regimen
Time frame: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Regimen B | Maximum Plasma Concentration (Cmax)-Formoterol | 18.1 pg/mL | Geometric Coefficient of Variation 58.4 |
| Regimen A | Maximum Plasma Concentration (Cmax)-Formoterol | 10.8 pg/mL | Geometric Coefficient of Variation 66.3 |
| Regimen C | Maximum Plasma Concentration (Cmax)-Formoterol | 8.3 pg/mL | Geometric Coefficient of Variation 98.6 |
| Regimen D | Maximum Plasma Concentration (Cmax)-Formoterol | 17.9 pg/mL | Geometric Coefficient of Variation 48.1 |
Primary
Maximum Plasma Concentration (Cmax)-Glycopyrronium
Maximum plasma concentration (Cmax) per Regimen
Time frame: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Regimen B | Maximum Plasma Concentration (Cmax)-Glycopyrronium | 47.7 pg/mL | Geometric Coefficient of Variation 73.3 |
| Regimen A | Maximum Plasma Concentration (Cmax)-Glycopyrronium | 19.0 pg/mL | Geometric Coefficient of Variation 131 |
| Regimen C | Maximum Plasma Concentration (Cmax)-Glycopyrronium | 17.1 pg/mL | Geometric Coefficient of Variation 181.7 |
| Regimen D | Maximum Plasma Concentration (Cmax)-Glycopyrronium | 42.1 pg/mL | Geometric Coefficient of Variation 65.4 |
Secondary
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Budesonide
Each treatment period is equal to assigned regimen
Time frame: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Regimen B | 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 |
| Regimen A | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Budesonide | 1491.8 h*pg/mL | Geometric Coefficient of Variation 64.4 |
| Regimen C | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Budesonide | 823.9 h*pg/mL | Geometric Coefficient of Variation 121.2 |
| Regimen D | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Budesonide | 1806.2 h*pg/mL | Geometric Coefficient of Variation 39.1 |
Secondary
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Formoterol
Each treatment period is equal to assigned regimen
Time frame: 24 hrs
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Regimen B | 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 |
| Regimen A | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Formoterol | 62.7 h*pg/mL | Geometric Coefficient of Variation 62.2 |
| Regimen C | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Formoterol | 62.6 h*pg/mL | Geometric Coefficient of Variation 55 |
| Regimen D | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Formoterol | 62.0 h*pg/mL | Geometric Coefficient of Variation 42.2 |
Secondary
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Glycopyrronium
Each treatment period is equal to assigned regimen
Time frame: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Regimen B | 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 |
| Regimen A | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Glycopyrronium | 65.9 h*pg/mL | Geometric Coefficient of Variation 44.7 |
| Regimen C | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Glycopyrronium | 15.2 h*pg/mL | Geometric Coefficient of Variation 54.5 |
| Regimen D | Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Glycopyrronium | 39.2 h*pg/mL | Geometric Coefficient of Variation 96.5 |
Secondary
Time to Maximum Plasma Concentration (Tmax)-Budesonide
Each treatment period is equal to assigned regimen
Time frame: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regimen B | Time to Maximum Plasma Concentration (Tmax)-Budesonide | 0.33 h (hour) |
| Regimen A | Time to Maximum Plasma Concentration (Tmax)-Budesonide | 0.33 h (hour) |
| Regimen C | Time to Maximum Plasma Concentration (Tmax)-Budesonide | 0.33 h (hour) |
| Regimen D | Time to Maximum Plasma Concentration (Tmax)-Budesonide | 0.33 h (hour) |
Secondary
Time to Maximum Plasma Concentration (Tmax)-Formoterol
Each treatment period is equal to assigned regimen
Time frame: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regimen B | Time to Maximum Plasma Concentration (Tmax)-Formoterol | 0.10 h (hour) |
| Regimen A | Time to Maximum Plasma Concentration (Tmax)-Formoterol | 0.10 h (hour) |
| Regimen C | Time to Maximum Plasma Concentration (Tmax)-Formoterol | 0.10 h (hour) |
| Regimen D | Time to Maximum Plasma Concentration (Tmax)-Formoterol | 0.10 h (hour) |
Secondary
Time to Maximum Plasma Concentration (Tmax)-Glycopyrronium
Each treatment period is equal to assigned regimen
Time frame: Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regimen B | Time to Maximum Plasma Concentration (Tmax)-Glycopyrronium | 0.03 h (hour) |
| Regimen A | Time to Maximum Plasma Concentration (Tmax)-Glycopyrronium | 0.03 h (hour) |
| Regimen C | Time to Maximum Plasma Concentration (Tmax)-Glycopyrronium | 0.03 h (hour) |
| Regimen D | Time to Maximum Plasma Concentration (Tmax)-Glycopyrronium | 0.03 h (hour) |