Asthma
Conditions
Keywords
inhalation profiles, pharmacokinetics, pharyngometry, asthma, pediatric subjects, GW685698, Fluticasone furoate, safety
Brief summary
This study will investigate the effect of dosing with flutucasone furoate in asthmatic subjects aged 5-11 years of age. A randomized, two-way crossover, with placebo control, over a 14 day treatment period, it will investigate safety, tolerability, pharmacokinetics and serum cortisol levels.
Detailed description
This study will investigate the effect of dosing with fluticasone furoate 100 μg (micrograms) in asthmatic subjects aged 5-11 years of age. Fluticasone furoate is currently under development as the inhaled corticosteroid component of a combination product containing an inhaled corticosteroid and a long-acting beta-agonist. The study will be a randomized two-way crossover, with a placebo control. During each treatment period subjects will receive a daily dose via a novel dry powder inhaler for 14 days. Approximately 26 subjects will be recruited to this study, with the aim that 20 will complete the study. Safety, tolerability, pharmacokinetics and serum cortisol levels will be investigated.
Interventions
DRUGFluticasone furoate
Novel dry powder inhaler: 100µg per blister One blister strip containing fluticasone furoate micronised drug blended with lactose and a second blister strip containing lactose and magnesium stearate.
DRUGMatching placebo
Novel dry powder inhaler: One blister strip containing lactose and a second blister strip containing lactose and magnesium stearate.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
5 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Male and pre-menarchial female subjects aged 5-11 years on the last planned treatment day are eligible for this study. Pre-menarchial females are defined as any female who has yet to begin menses and is considered Tanner Stage 2 or less. * Diagnosis of asthma at least 6 months prior to screening. * Patients must be controlled on their existing asthma treatment at screening as defined by a Childhood Asthma Control Test score of \>19 and PEF (Peak Expiratory Flow) ≥80% predicted. * Apart from asthma, eczema and rhinitis, subjects should be healthy and suffer from no other significant medical conditions. * Subjects must be taking a stable regimen of a short acting beta-agonist inhaler on an as-need basis for at least 4 weeks prior to screening. * Subjects must weigh at least 15 kg (kilograms). * Subjects must demonstrate ability to accept and effectively use the fluticasone furoate devices using the demonstration kits provided to the site. * Subjects and parents/guardians must be able to understand and comply with protocol requirements, instructions and protocol-stated restrictions. Parents/guardians must have the ability to read, write and record diary information collected throughout the study. They must also have the ability to manage study drug administration and PEF assessments. * A signed and dated written informed consent from at least one parent/guardian, and accompanying informed assent from the subject prior to admission to the study.
Exclusion criteria
* Subjects who have changed their asthma medication within 4 weeks of screening or subjects currently being treated with inhaled corticosteroids or have received such treatment within 4 weeks of screening. In addition, subjects currently receiving (or have received within 4 weeks of screening) any of the following asthma therapies: theophyllines, long-acting inhaled beta-agonists or oral beta-agonists. * Any medical condition or circumstance making the volunteer unsuitable for participation in the study (e.g. history of life-threatening asthma). * Any clinically relevant abnormality identified on the screening medical assessment, including asthma exacerbation requiring systemic corticosteroids (oral, intramuscular, intravenous) or emergency room attendance within 3 months or asthma exacerbation requiring hospitalization within 6 months prior to screening. * Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks of screening and led to a change in asthma management or, in the opinion of the Investigator, is expected to affect the subject's asthma status or the subject's ability to participate in the study. * Clinical visual evidence of oral candidiasis at screening. * Parent/guardian has history of psychiatric disease, intellectual deficiency, substance abuse, or other condition (e.g., inability to read, comprehend and write) which will limit the validity of consent to participate in this study. * Any adverse reaction including immediate or delayed hypersensitivity to any beta-2-agonist, sympathomimetic drug, or any intranasal, inhaled or systemic corticosteroid therapy. * Known or suspected sensitivity to the constituents of the novel dry powder inhaler (i.e., lactose or magnesium stearate), for example, history of severe milk protein allergy. * A subject will not be eligible for this study if he/she is an immediate family member of the participating Investigator, sub-Investigator, study coordinator, or employee of the participating Investigator. * Children who are wards of the state or government. * Evidence of clinically significant abnormality in the 12-lead ECG (electrocardiogram) at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Baseline and Day 14 of the respective treatment period (up to Study Day 44) | PR, QRS, QT, QTcB, QTcF, and RR were measured at Baseline and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1 for each period. Change from Baseline was calculated as the value at Day 14 minus the Baseline value. QTcB is the QT duration corrected for heart rate by Bazett's formula. QTcF is the QT duration corrected for heart rate by Fridericia's formula. |
| Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 44) | Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelets, and white blood cell (WBC) count at Day 14 of the respective treatment period. |
| Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Values at Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 44) | Blood samples were collected for the measurement of hemoglobin and MCHC at Day 14 of the respective treatment period. |
| Reticulocyte and Red Blood Cell (RBC) Values at Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 44) | Blood samples were collected for the measurement of reticulocyte and RBCs at Day 14 of the respective treatment period. |
| Hematocrit Values at Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 44) | Blood samples were collected for the measurement of hematocrit at Day 14 of the respective treatment period. Hematocrit is a measure of the percentage of the volume of the whole blood that is composed of red blood cells, as determined by separation of red blood cells from the plasma (usually by centrifugation). |
| Mean Corpuscle Volume (MCV) Value at Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 44) | Blood samples were collected for the measurement of MCV at Day 14 of the respective treatment period. |
| Mean Corpuscle Hemoglobin (MCH) Values at Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 44) | Blood samples were collected for the measurement of MCH at Day 14 of the respective treatment period. |
| Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) Values at Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 44) | Blood samples were collected for the measurement of ALT, ALP, AST, and GGT at Day 14 of the respective treatment period. |
| Albumin and Total Protein Values at Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 44) | Blood samples were collected for the measurement of albumin and total protein at Day 14 of the respective treatment period. |
| Calcium, Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 44) | Blood samples were collected for the measurement of calcium, chloride, carbon dioxide content/bicarbonate (CO2/BI), glucose, potassium, sodium, and urea/BUN at Day 14 of the respective treatment period. |
| Total Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 44) | Blood samples were collected for the measurement of total bilirubin, creatinine, and uric acid at Day 14 of the respective treatment period. |
| Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 1 and Day 14 of the respective treatment period (up to Study Day 44) | Peak Expiratory Flow (PEF) is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF is calculated as the maximum of three readings taken at each timepoint for each participant. Baseline is defined as the maximum pre-dose measurement at Day 1 for each period. |
| Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Baseline and Day 14 of the respective treatment period (up to Study Day 44) | SBP and DBP were measured at Baseline and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1 for each period. |
| Heart Rate at Baseline and Day 14 of the Respective Treatment Period | Baseline and Day 14 of the respective treatment period (up to Study Day 44) | Heart rate (HR) was measured at Baseline and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1 for each period. |
| Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period | From the start of study medication until Week 11 (Visit 6)/Early Withdrawal | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in deciding whether reporting is appropriate in other situations. Refer to the General Adverse AE/SAE module for a complete list of AEs and SAEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax on Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period | Cmax is defined as the maximum observed concentration on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period. |
| Tmax and t at Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period | tmax is defined as the time to reach the observed maximum concentration, and t is defined as the time of the last observed quantifiable concentration on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period. |
| Serum Cortisol Weighted Mean (0-12 Hours) on Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period | Serum cortisol weighted mean was determined for each participant over the time period 0-12 hours on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period. |
| Average Oropharyngeal Cross-sectional Area on Days 1 and 14 of the Respective Treatment Period | Days 1 and 14 of the respective treatment period | During the pharyngometry assessment, participants inhaled through a wavetube, which had a mouthpiece with the same dimensions as the mouthpiece on the dry powder inhaler used for this study. This technique was used to measure the size of the throat and mouth (oropharynx) in the form of pharyngograms. Pharyngometry data were recorded for each day (Days 1 and 14 of the respective treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated. |
| Distance of Assessment on Days 1 and 14 of the Respective Treatment Period | Days 1 and 14 of the respective treatment period | During the pharyngometry assessment, participants inhaled through a wavetube, which had a mouthpiece with the same dimensions as the mouthpiece on the dry powder inhaler used for this study. This technique was used to measure the size of the throat and mouth (oropharynx) in the form of pharyngograms. Distance of assessment is defined as the distance (length measured in centimeters \[cm\]) estimated to be from the lips to the larynx. Pharyngometry data were recorded for each day (Days 1 and 14 of each treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated. |
| Oropharyngeal Volume on Days 1 and 14 of the Respective Treatment Period | Days 1 and 14 of the respective treatment period | During the pharyngometry assessment, participants inhaled through a wavetube, which had a mouthpiece with the same dimensions as the mouthpiece on the dry powder inhaler used for this study. This technique was used to measure the size of the throat and mouth (oropharynx) in the form of pharyngograms. Oropharyngeal volume is defined as the volume (cm\^3) of the mouth and throat estimated to be from the lips to the larynx. Pharyngometry data were recorded for each day (Days 1 and 14 of the respective treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated. |
| Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Days 1 and 14 of the Respective Treatment Period | Day 1 and Day 14 of the respective treatment period | During the inhalation profile assessment, participants inhaled through a mouthpiece from a device with a similar resistance to the dry powder inhaler used for this study. Average flow rate is defined as the average inspiratory flow rate (Liters \[L\]/min) across the inhalation profile when inhaling across the resistance of the inhaler. PIFR is defined as the Peak Inspiratory Flow Rate (L/min) of the inhalation profile when inhaling across the resistance of the inhaler.The pressure drop during the inhalation was measured, and the inhalation profiles (pressure drop versus time profile) of the participants were obtained. The mean of the two inhalation profile measurements was used for each day (Days 1 and 14 of the respective treatment period), and the average flow rate and PIFR were determined. |
| Inhalation Time on Days 1 and 14 of the Respective Treatment Period | Day 1 and Day 14 of the respective treatment period | During the inhalation profile assessment, participants inhaled through a mouthpiece from a device with a similar resistance to the dry powder inhaler used for this study. Inhalation time is defined as the duration of the inhalation(s) when inhaling across the resistance of the inhaler. The pressure drop during the inhalation was measured, and the inhalation profiles (pressure drop versus time profile) of the participants were obtained. The mean of the two inhalation profile measurements was used for each day (Days 1 and 14 of the respective treatment period), and the inhalation time was determined. |
| Inhaled Volume on Days 1 and 14 of the Respective Treatment Period | Day 1 and Day 14 of the respective treatment period | During the inhalation profile assessment, participants inhaled through a mouthpiece from a device with a similar resistance to the dry powder inhaler used for this study. Inhaled volume is defined as the volume of air (Liters) inhaled during the inhalation across the resistance of the inhaler. The pressure drop during the inhalation was measured, and the inhalation profiles (pressure drop versus time profile) of the participants were obtained. The mean of the two inhalation profile measurements was used for each day (Days 1 and 14 of the respective treatment period), and the inhalaled volume was determined. |
| Peak Pressure Drop on Days 1 and 14 of the Respective Treatment Period | Day 1 and Day 14 of the respective treatment period | During the inhalation profile assessment, participants inhaled through a mouthpiece from a device with a similar resistance to the dry powder inhaler used for this study. Peak pressure drop is defined as the maximum pressure drop (kilopascal \[kPa\]) achieved during inhalation across the resistance of the inhaler. The pressure drop during the inhalation was measured, and the inhalation profiles (pressure drop versus time profile) of the participants were obtained. The mean of the two inhalation profile measurements was calculated for each day (Days 1 and 14 of the respective treatment period), and used for subsequent modeling and prediction of dose emission attributes. |
| Total Emitted Dose (TED) on Days 1 and 14 of the Respective Treatment Period | Day 1 and Day 14 of the respective treatment period | The total emitted dose (TED) is defined as the mass (micrograms) of the nominal dose that passes beyond the throat. The recorded inhalation profiles of the participants and the mouth-throat (oropharyngeal) models of the sizes that approximated to pharyngometry measurements of the participants were used in conjunction with the electronic Lung (eLung) for in vitro assessment. The eLung is a breathing simulator that replicates the selected inhalation profile with an active inhaler placed at the lips end of the selected ororpharyngeal model. After the dose is emitted from the inhaler, the analysis and assay of throat deposition and material passing beyond the throat was used to derive the nominal, minimum, and maximum predicted total emitted dose. |
| Ex-throat Dose (ETD) and ETD <2 Microns on Days 1 and 14 of the Respective Treatment Period | Day 1 and Day 14 of the respective treatment period | The ex-throat dose (ETD) and the nominal ETD is the mass (micrograms) of active investigational material that passes beyond the throat, nominal being the mean.The recorded inhalation profiles of the participants and the mouth-throat (oropharyngeal) models of the sizes that approximated to pharyngometry measurements of the participants were used in conjunction with the electronic Lung (eLung) for in vitro assessment. The eLung is a breathing simulator that replicates the selected inhalation profile with an active inhaler placed at the lips end of the selected ororpharyngeal model. After the dose is emitted from the inhaler, the analysis and assay of throat deposition and material passing beyond the throat was used to derive the nominal, minimum, and maximum predicted ETD and ETD \<2 microns. |
| AUC(0-t) on Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period | Area under the concentration-time (AUC(0-t)) curve from time zero (pre-dose) to the last time of quantifiable concentration of FF on Day 14 of the respective treatment period was measured. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period. Due to non-quantifiable values, it was not possible to derive AUC(0-12). |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled into one of two cohorts based upon age; the younger cohort was enrolled after a review of the safety/pharmacokinetic data of at least six participants from the older cohort. Each participant was assigned to treatment randomly; assignment was not to be influenced by whether participants were in Cohort 1 or Cohort 2.
Pre-assignment details
A Baseline assessment was carried out on Day 1 of the first treatment period. Participants were then randomized to one of the two possible treatment sequences (fluticasone furoate \[FF\] 100 µg followed by placebo; placebo followed by FF 100 µg). Results are reported by intervention, regardless of the age of the participant.
Participants by arm
| Arm | Count |
|---|---|
| FF 100 µg/Placebo or Placebo/FF 100 µg Participants received either fluticasone furoate (FF) 100 micrograms (µg) or matching placebo in the first of two 14-day treatment periods, followed by the other therapy (the therapy not received in the first treatment period) in the second 14-day treatment period. Inhaled FF 100 µg or matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days. | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1 (14 Days) | Adverse Event | 1 | 0 |
| Treatment Period 1 (14 Days) | Protocol Violation | 1 | 1 |
| Treatment Period 2 (14 Days) | Physician Decision | 1 | 1 |
Baseline characteristics
| Characteristic | FF 100 µg/Placebo or Placebo/FF 100 µg |
|---|---|
| Age, Continuous | 8.2 Years STANDARD_DEVIATION 2.08 |
| Race/Ethnicity, Customized African American/African Heritage | 9 participants |
| Race/Ethnicity, Customized African American/African Heritage & White | 1 participants |
| Race/Ethnicity, Customized Unknown; Child Was Adopted | 1 participants |
| Race/Ethnicity, Customized White | 16 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 25 | 8 / 26 |
| serious Total, serious adverse events | 0 / 25 | 0 / 26 |
Outcome results
Primary
Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) Values at Day 14 of the Respective Treatment Period
Blood samples were collected for the measurement of ALT, ALP, AST, and GGT at Day 14 of the respective treatment period.
Time frame: Day 14 of the respective treatment period (up to Study Day 44)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) Values at Day 14 of the Respective Treatment Period | ALP, n=22, 20 | 257.8 International units per liter (IU/L) | Standard Deviation 59.24 |
| Placebo | Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) Values at Day 14 of the Respective Treatment Period | ALT, n=22, 20 | 12.2 International units per liter (IU/L) | Standard Deviation 3.06 |
| Placebo | Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) Values at Day 14 of the Respective Treatment Period | AST, n=22, 19 | 26.8 International units per liter (IU/L) | Standard Deviation 4.39 |
| Placebo | Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) Values at Day 14 of the Respective Treatment Period | GGT, n=22, 20 | 14.3 International units per liter (IU/L) | Standard Deviation 3.58 |
| FF 100 µg | Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) Values at Day 14 of the Respective Treatment Period | GGT, n=22, 20 | 15.4 International units per liter (IU/L) | Standard Deviation 4.5 |
| FF 100 µg | Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) Values at Day 14 of the Respective Treatment Period | ALT, n=22, 20 | 13.0 International units per liter (IU/L) | Standard Deviation 6.04 |
| FF 100 µg | Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) Values at Day 14 of the Respective Treatment Period | ALP, n=22, 20 | 260.7 International units per liter (IU/L) | Standard Deviation 64.15 |
| FF 100 µg | Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) Values at Day 14 of the Respective Treatment Period | AST, n=22, 19 | 26.1 International units per liter (IU/L) | Standard Deviation 4.53 |
Primary
Albumin and Total Protein Values at Day 14 of the Respective Treatment Period
Blood samples were collected for the measurement of albumin and total protein at Day 14 of the respective treatment period.
Time frame: Day 14 of the respective treatment period (up to Study Day 44)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Albumin and Total Protein Values at Day 14 of the Respective Treatment Period | Albumin, n=22, 20 | 43.0 Grams per liter | Standard Deviation 2.26 |
| Placebo | Albumin and Total Protein Values at Day 14 of the Respective Treatment Period | Total protein, n=22, 20 | 67.8 Grams per liter | Standard Deviation 2.98 |
| FF 100 µg | Albumin and Total Protein Values at Day 14 of the Respective Treatment Period | Albumin, n=22, 20 | 42.9 Grams per liter | Standard Deviation 1.83 |
| FF 100 µg | Albumin and Total Protein Values at Day 14 of the Respective Treatment Period | Total protein, n=22, 20 | 67.8 Grams per liter | Standard Deviation 2.57 |
Primary
Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period
Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelets, and white blood cell (WBC) count at Day 14 of the respective treatment period.
Time frame: Day 14 of the respective treatment period (up to Study Day 44)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | Total neutrophils, n=23, 21 | 2.740 10^9 cells per liter (GI/L) | Standard Deviation 1.2091 |
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | Monocytes, n=23, 21 | 0.280 10^9 cells per liter (GI/L) | Standard Deviation 0.1669 |
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | Eosinophils, n=23, 21 | 0.308 10^9 cells per liter (GI/L) | Standard Deviation 0.2204 |
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | Platelets, n=23, 20 | 266.4 10^9 cells per liter (GI/L) | Standard Deviation 48.59 |
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | Basophils, n=23, 21 | 0.022 10^9 cells per liter (GI/L) | Standard Deviation 0.0153 |
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | WBCs, n=23, 21 | 5.94 10^9 cells per liter (GI/L) | Standard Deviation 1.696 |
| Placebo | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | Lymphocytes, n=23, 21 | 2.595 10^9 cells per liter (GI/L) | Standard Deviation 0.7834 |
| FF 100 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | WBCs, n=23, 21 | 6.18 10^9 cells per liter (GI/L) | Standard Deviation 1.513 |
| FF 100 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | Basophils, n=23, 21 | 0.022 10^9 cells per liter (GI/L) | Standard Deviation 0.0154 |
| FF 100 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | Eosinophils, n=23, 21 | 0.252 10^9 cells per liter (GI/L) | Standard Deviation 0.2182 |
| FF 100 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | Lymphocytes, n=23, 21 | 2.430 10^9 cells per liter (GI/L) | Standard Deviation 0.6563 |
| FF 100 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | Total neutrophils, n=23, 21 | 3.209 10^9 cells per liter (GI/L) | Standard Deviation 1.3103 |
| FF 100 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | Platelets, n=23, 20 | 263.3 10^9 cells per liter (GI/L) | Standard Deviation 55.9 |
| FF 100 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | Monocytes, n=23, 21 | 0.270 10^9 cells per liter (GI/L) | Standard Deviation 0.1204 |
Primary
Calcium, Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 14 of the Respective Treatment Period
Blood samples were collected for the measurement of calcium, chloride, carbon dioxide content/bicarbonate (CO2/BI), glucose, potassium, sodium, and urea/BUN at Day 14 of the respective treatment period.
Time frame: Day 14 of the respective treatment period (up to Study Day 44)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Calcium, Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 14 of the Respective Treatment Period | Urea/BUN, n=22, 20 | 4.66 Millimoles per liter (mmol/L) | Standard Deviation 0.993 |
| Placebo | Calcium, Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 14 of the Respective Treatment Period | Glucose, n=22, 20 | 5.13 Millimoles per liter (mmol/L) | Standard Deviation 0.614 |
| Placebo | Calcium, Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 14 of the Respective Treatment Period | Chloride, n=22, 20 | 105.2 Millimoles per liter (mmol/L) | Standard Deviation 1.93 |
| Placebo | Calcium, Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 14 of the Respective Treatment Period | Potassium, n=20, 19 | 4.24 Millimoles per liter (mmol/L) | Standard Deviation 0.2564 |
| Placebo | Calcium, Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 14 of the Respective Treatment Period | Calcium, n=20, 19 | 2.371 Millimoles per liter (mmol/L) | Standard Deviation 0.0791 |
| Placebo | Calcium, Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 14 of the Respective Treatment Period | Sodium, n=22, 20 | 138.3 Millimoles per liter (mmol/L) | Standard Deviation 1.55 |
| Placebo | Calcium, Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 14 of the Respective Treatment Period | CO2 content/bicarbonate, n=20, 19 | 17.4 Millimoles per liter (mmol/L) | Standard Deviation 2.04 |
| FF 100 µg | Calcium, Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 14 of the Respective Treatment Period | Urea/BUN, n=22, 20 | 4.83 Millimoles per liter (mmol/L) | Standard Deviation 1.331 |
| FF 100 µg | Calcium, Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 14 of the Respective Treatment Period | Calcium, n=20, 19 | 2.366 Millimoles per liter (mmol/L) | Standard Deviation 0.0626 |
| FF 100 µg | Calcium, Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 14 of the Respective Treatment Period | Chloride, n=22, 20 | 104.7 Millimoles per liter (mmol/L) | Standard Deviation 1.72 |
| FF 100 µg | Calcium, Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 14 of the Respective Treatment Period | CO2 content/bicarbonate, n=20, 19 | 17.8 Millimoles per liter (mmol/L) | Standard Deviation 1.86 |
| FF 100 µg | Calcium, Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 14 of the Respective Treatment Period | Glucose, n=22, 20 | 4.86 Millimoles per liter (mmol/L) | Standard Deviation 0.319 |
| FF 100 µg | Calcium, Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 14 of the Respective Treatment Period | Potassium, n=20, 19 | 4.24 Millimoles per liter (mmol/L) | Standard Deviation 0.289 |
| FF 100 µg | Calcium, Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 14 of the Respective Treatment Period | Sodium, n=22, 20 | 137.4 Millimoles per liter (mmol/L) | Standard Deviation 1.54 |
Primary
Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period
PR, QRS, QT, QTcB, QTcF, and RR were measured at Baseline and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1 for each period. Change from Baseline was calculated as the value at Day 14 minus the Baseline value. QTcB is the QT duration corrected for heart rate by Bazett's formula. QTcF is the QT duration corrected for heart rate by Fridericia's formula.
Time frame: Baseline and Day 14 of the respective treatment period (up to Study Day 44)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcF Interval, Predose, n=24, 23 | 14.2 milliseconds (msec) | Standard Deviation 9.92 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 PR Interval, 7 hour, n=23, 23 | 8.3 milliseconds (msec) | Standard Deviation 6.56 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QRS Interval, 1 hour, n=23, 23 | 5.7 milliseconds (msec) | Standard Deviation 3.54 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QRS Interval, 4 hours, n=23, 23 | 5.6 milliseconds (msec) | Standard Deviation 3.85 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QRS Interval, 7 hours, n=23, 23 | 6.1 milliseconds (msec) | Standard Deviation 5.25 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QT Interval, 4 hours, n=23, 23 | 13.3 milliseconds (msec) | Standard Deviation 9.65 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcB Interval, 4 hours, n=23, 23 | 14.7 milliseconds (msec) | Standard Deviation 9.13 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcF Interval, 7 hours, n=23, 23 | 9.3 milliseconds (msec) | Standard Deviation 7.77 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcF Interval, 12 hours, n=23, 23 | 8.8 milliseconds (msec) | Standard Deviation 5.84 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 RR Interval, 1 hour, n=25, 26 | 93.5 milliseconds (msec) | Standard Deviation 64.97 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 PR Interval, Predose, n=24, 23 | 7.8 milliseconds (msec) | Standard Deviation 6.76 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 PR Interval, 1 hour, n=23, 23 | 8.7 milliseconds (msec) | Standard Deviation 6.74 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 PR Interval, 12 hours, n=22, 23 | 7.2 milliseconds (msec) | Standard Deviation 7.5 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QRS Interval, 30 minutes, n=25, 26 | 4.6 milliseconds (msec) | Standard Deviation 3.46 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QRS Interval, 1 hour, n=25, 26 | 4.1 milliseconds (msec) | Standard Deviation 2.84 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QRS Interval, 2 hours, n=25, 26 | 4.0 milliseconds (msec) | Standard Deviation 2.64 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QRS Interval, Predose, n=24, 23 | 4.2 milliseconds (msec) | Standard Deviation 3.71 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QRS Interval, 12 hours, n=23, 23 | 5.0 milliseconds (msec) | Standard Deviation 4.7 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QT Interval, 30 minutes, n=25, 26 | 9.8 milliseconds (msec) | Standard Deviation 8.14 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QT Interval, 1 hour, n=25, 26 | 13.1 milliseconds (msec) | Standard Deviation 11.04 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QT Interval, 2 hours, n=25, 26 | 17.5 milliseconds (msec) | Standard Deviation 13.88 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QT Interval, Predose, n=24, 23 | 12.5 milliseconds (msec) | Standard Deviation 9.81 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QT Interval, 1 hour, n=23, 23 | 11.4 milliseconds (msec) | Standard Deviation 6.45 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QT Interval, 7 hours, n=23, 23 | 14.7 milliseconds (msec) | Standard Deviation 10.94 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QT Interval, 12 hours, n=23, 23 | 14.7 milliseconds (msec) | Standard Deviation 10.42 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QTcB Interval, 30 minutes, n=25, 26 | 15.4 milliseconds (msec) | Standard Deviation 14.44 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QTcB Interval, 1 hour, n=25, 26 | 17.3 milliseconds (msec) | Standard Deviation 13.46 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QTcB Interval, 2 hours, n=25, 26 | 13.6 milliseconds (msec) | Standard Deviation 11.07 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcB Interval, Predose, n=24, 23 | 20.7 milliseconds (msec) | Standard Deviation 15.54 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcB Interval, 1 hour, n=23, 23 | 16.6 milliseconds (msec) | Standard Deviation 9.43 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcB Interval, 7 hours, n=23, 23 | 14.5 milliseconds (msec) | Standard Deviation 10.14 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcB Interval, 12 hours, n=23, 23 | 13.8 milliseconds (msec) | Standard Deviation 10.7 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QTcF Interval, 30 minutes, n=25, 26 | 10.8 milliseconds (msec) | Standard Deviation 9.31 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QTcF Interval, 1 hour, n=25, 26 | 11.6 milliseconds (msec) | Standard Deviation 9.57 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QTcF Interval, 2 hours, n=25, 26 | 10.4 milliseconds (msec) | Standard Deviation 8.36 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 PR Interval, 4 hours, n=23, 23 | 6.4 milliseconds (msec) | Standard Deviation 3.7 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcF Interval, 1 hour, n=23, 23 | 9.3 milliseconds (msec) | Standard Deviation 6.09 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcF Interval, 4 hours, n=23, 23 | 7.8 milliseconds (msec) | Standard Deviation 6.97 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 PR Interval, 30 minutes, n=25, 26 | 6.4 milliseconds (msec) | Standard Deviation 6.37 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 RR Interval, 30 minutes, n=25, 26 | 70.4 milliseconds (msec) | Standard Deviation 66.47 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 PR Interval, 1 hour, n=25, 26 | 7.3 milliseconds (msec) | Standard Deviation 6.68 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 RR Interval, 2 hours, n=25, 26 | 102.0 milliseconds (msec) | Standard Deviation 61.66 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 RR Interval, Predose, n=24, 23 | 106.0 milliseconds (msec) | Standard Deviation 73.2 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 RR Interval, 1 hour, n=23, 23 | 92.5 milliseconds (msec) | Standard Deviation 64.45 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 RR Interval, 4 hours, n=23, 23 | 92.1 milliseconds (msec) | Standard Deviation 65.93 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 RR Interval, 7 hours, n=23, 23 | 89.6 milliseconds (msec) | Standard Deviation 63.06 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 RR Interval, 12 hours, n=23, 23 | 94.4 milliseconds (msec) | Standard Deviation 73.45 |
| Placebo | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 PR Interval, 2 hours, n=25, 26 | 8.0 milliseconds (msec) | Standard Deviation 8.61 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 RR Interval, 7 hours, n=23, 23 | 74.5 milliseconds (msec) | Standard Deviation 78.18 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QT Interval, 7 hours, n=23, 23 | 15.3 milliseconds (msec) | Standard Deviation 11.93 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QRS Interval, 1 hour, n=25, 26 | 4.4 milliseconds (msec) | Standard Deviation 3.86 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 RR Interval, Predose, n=24, 23 | 103.5 milliseconds (msec) | Standard Deviation 78.48 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QT Interval, 12 hours, n=23, 23 | 24.8 milliseconds (msec) | Standard Deviation 14.93 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QRS Interval, 4 hours, n=23, 23 | 4.9 milliseconds (msec) | Standard Deviation 3.93 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcF Interval, 1 hour, n=23, 23 | 11.4 milliseconds (msec) | Standard Deviation 9.56 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QRS Interval, 7 hours, n=23, 23 | 4.3 milliseconds (msec) | Standard Deviation 4.22 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QTcB Interval, 30 minutes, n=25, 26 | 14.2 milliseconds (msec) | Standard Deviation 11.64 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 PR Interval, 2 hours, n=25, 26 | 9.5 milliseconds (msec) | Standard Deviation 10.48 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcB Interval, 4 hours, n=23, 23 | 16.8 milliseconds (msec) | Standard Deviation 9.23 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QTcF Interval, 2 hours, n=25, 26 | 15.4 milliseconds (msec) | Standard Deviation 12.88 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcF Interval, Predose, n=24, 23 | 12.6 milliseconds (msec) | Standard Deviation 10.99 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcF Interval, 4 hours, n=23, 23 | 15.7 milliseconds (msec) | Standard Deviation 7.41 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QTcB Interval, 1 hour, n=25, 26 | 17.7 milliseconds (msec) | Standard Deviation 13.18 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcF Interval, 7 hours, n=23, 23 | 15.0 milliseconds (msec) | Standard Deviation 9.51 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 RR Interval, 1 hour, n=23, 23 | 87.7 milliseconds (msec) | Standard Deviation 63.3 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcF Interval, 12 hours, n=23, 23 | 15.8 milliseconds (msec) | Standard Deviation 11.61 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QTcB Interval, 2 hours, n=25, 26 | 18.2 milliseconds (msec) | Standard Deviation 17.54 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 PR Interval, 30 minutes, n=25, 26 | 7.5 milliseconds (msec) | Standard Deviation 7.54 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 PR Interval, Predose, n=24, 23 | 9.6 milliseconds (msec) | Standard Deviation 9.82 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcB Interval, Predose, n=24, 23 | 17.9 milliseconds (msec) | Standard Deviation 14.92 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 PR Interval, 1 hour, n=23, 23 | 8.3 milliseconds (msec) | Standard Deviation 6.03 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 PR Interval, 4 hours, n=23, 23 | 8.9 milliseconds (msec) | Standard Deviation 6.86 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 PR Interval, 7 hour, n=23, 23 | 10.2 milliseconds (msec) | Standard Deviation 10.09 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 RR Interval, 12 hours, n=23, 23 | 110.3 milliseconds (msec) | Standard Deviation 101.24 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 PR Interval, 12 hours, n=22, 23 | 9.7 milliseconds (msec) | Standard Deviation 6.54 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcB Interval, 1 hour, n=23, 23 | 16.2 milliseconds (msec) | Standard Deviation 9.71 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QRS Interval, 30 minutes, n=25, 26 | 5.2 milliseconds (msec) | Standard Deviation 4.7 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 RR Interval, 4 hours, n=23, 23 | 63.6 milliseconds (msec) | Standard Deviation 47.14 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcB Interval, 7 hours, n=23, 23 | 19.6 milliseconds (msec) | Standard Deviation 12.03 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QRS Interval, 2 hours, n=25, 26 | 4.5 milliseconds (msec) | Standard Deviation 3.61 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 RR Interval, 30 minutes, n=25, 26 | 54.2 milliseconds (msec) | Standard Deviation 44.61 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QRS Interval, Predose, n=24, 23 | 4.7 milliseconds (msec) | Standard Deviation 4.29 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QRS Interval, 1 hour, n=23, 23 | 5.3 milliseconds (msec) | Standard Deviation 4.71 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QTcB Interval, 12 hours, n=23, 23 | 18.5 milliseconds (msec) | Standard Deviation 15.7 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QRS Interval, 12 hours, n=23, 23 | 4.8 milliseconds (msec) | Standard Deviation 4.02 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 RR Interval, 1 hour, n=25, 26 | 90.7 milliseconds (msec) | Standard Deviation 52.94 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QT Interval, 30 minutes, n=25, 26 | 10.5 milliseconds (msec) | Standard Deviation 9.57 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QTcF Interval, 30 minutes, n=25, 26 | 11.8 milliseconds (msec) | Standard Deviation 9.3 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QT Interval, 1 hour, n=25, 26 | 12.7 milliseconds (msec) | Standard Deviation 11.53 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 PR Interval, 1 hour, n=25, 26 | 8.4 milliseconds (msec) | Standard Deviation 7.17 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QT Interval, 2 hours, n=25, 26 | 15.5 milliseconds (msec) | Standard Deviation 13.83 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 QTcF Interval, 1 hour, n=25, 26 | 12.6 milliseconds (msec) | Standard Deviation 10 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QT Interval, Predose, n=24, 23 | 15.5 milliseconds (msec) | Standard Deviation 13.34 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 1 RR Interval, 2 hours, n=25, 26 | 80.4 milliseconds (msec) | Standard Deviation 71.51 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QT Interval, 1 hour, n=23, 23 | 15.9 milliseconds (msec) | Standard Deviation 11.11 |
| FF 100 µg | Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period | Day 14 QT Interval, 4 hours, n=23, 23 | 16.7 milliseconds (msec) | Standard Deviation 12.52 |
Primary
Heart Rate at Baseline and Day 14 of the Respective Treatment Period
Heart rate (HR) was measured at Baseline and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1 for each period.
Time frame: Baseline and Day 14 of the respective treatment period (up to Study Day 44)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Heart Rate at Baseline and Day 14 of the Respective Treatment Period | Day 1, Baseline, n=25, 26 | 78.7 Beats per minute | Standard Deviation 13.18 |
| Placebo | Heart Rate at Baseline and Day 14 of the Respective Treatment Period | Day 14, Predose, n=24, 23 | 76.8 Beats per minute | Standard Deviation 13.52 |
| Placebo | Heart Rate at Baseline and Day 14 of the Respective Treatment Period | Day 1, 1 hour, n=25, 26 | 78.6 Beats per minute | Standard Deviation 12.62 |
| Placebo | Heart Rate at Baseline and Day 14 of the Respective Treatment Period | Day 14, 1 hour, n=23, 23 | 80.3 Beats per minute | Standard Deviation 14.76 |
| Placebo | Heart Rate at Baseline and Day 14 of the Respective Treatment Period | Day 1, 30 minutes, n=25, 26 | 78.5 Beats per minute | Standard Deviation 13.99 |
| Placebo | Heart Rate at Baseline and Day 14 of the Respective Treatment Period | Day 14, 7 hours, n=23, 23 | 83.1 Beats per minute | Standard Deviation 14.65 |
| Placebo | Heart Rate at Baseline and Day 14 of the Respective Treatment Period | Day 1, 2 hours, n=25, 26 | 80.6 Beats per minute | Standard Deviation 13.3 |
| Placebo | Heart Rate at Baseline and Day 14 of the Respective Treatment Period | Day 14, 12 hours, n=23, 23 | 83.6 Beats per minute | Standard Deviation 11.7 |
| Placebo | Heart Rate at Baseline and Day 14 of the Respective Treatment Period | Day 14, 4 hours, n=23, 23 | 78.2 Beats per minute | Standard Deviation 10.46 |
| FF 100 µg | Heart Rate at Baseline and Day 14 of the Respective Treatment Period | Day 14, 12 hours, n=23, 23 | 81.1 Beats per minute | Standard Deviation 10.71 |
| FF 100 µg | Heart Rate at Baseline and Day 14 of the Respective Treatment Period | Day 14, 4 hours, n=23, 23 | 77.7 Beats per minute | Standard Deviation 9.77 |
| FF 100 µg | Heart Rate at Baseline and Day 14 of the Respective Treatment Period | Day 1, Baseline, n=25, 26 | 75.9 Beats per minute | Standard Deviation 11.48 |
| FF 100 µg | Heart Rate at Baseline and Day 14 of the Respective Treatment Period | Day 1, 30 minutes, n=25, 26 | 75.5 Beats per minute | Standard Deviation 10.9 |
| FF 100 µg | Heart Rate at Baseline and Day 14 of the Respective Treatment Period | Day 1, 1 hour, n=25, 26 | 77.6 Beats per minute | Standard Deviation 11.49 |
| FF 100 µg | Heart Rate at Baseline and Day 14 of the Respective Treatment Period | Day 1, 2 hours, n=25, 26 | 79.6 Beats per minute | Standard Deviation 11.78 |
| FF 100 µg | Heart Rate at Baseline and Day 14 of the Respective Treatment Period | Day 14, Predose, n=24, 23 | 74.5 Beats per minute | Standard Deviation 10.6 |
| FF 100 µg | Heart Rate at Baseline and Day 14 of the Respective Treatment Period | Day 14, 1 hour, n=23, 23 | 76.2 Beats per minute | Standard Deviation 8.6 |
| FF 100 µg | Heart Rate at Baseline and Day 14 of the Respective Treatment Period | Day 14, 7 hours, n=23, 23 | 81.2 Beats per minute | Standard Deviation 12.13 |
Primary
Hematocrit Values at Day 14 of the Respective Treatment Period
Blood samples were collected for the measurement of hematocrit at Day 14 of the respective treatment period. Hematocrit is a measure of the percentage of the volume of the whole blood that is composed of red blood cells, as determined by separation of red blood cells from the plasma (usually by centrifugation).
Time frame: Day 14 of the respective treatment period (up to Study Day 44)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Hematocrit Values at Day 14 of the Respective Treatment Period | 0.3840 percentage of red blood cells in blood | Standard Deviation 0.02621 |
| FF 100 µg | Hematocrit Values at Day 14 of the Respective Treatment Period | 0.3854 percentage of red blood cells in blood | Standard Deviation 0.02296 |
Primary
Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Values at Day 14 of the Respective Treatment Period
Blood samples were collected for the measurement of hemoglobin and MCHC at Day 14 of the respective treatment period.
Time frame: Day 14 of the respective treatment period (up to Study Day 44)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Values at Day 14 of the Respective Treatment Period | Hemoglobin, n=23, 21 | 129.1 Grams per liter (g/L) | Standard Deviation 7.15 |
| Placebo | Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Values at Day 14 of the Respective Treatment Period | MCHC, n=23, 21 | 336.4 Grams per liter (g/L) | Standard Deviation 7.66 |
| FF 100 µg | Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Values at Day 14 of the Respective Treatment Period | Hemoglobin, n=23, 21 | 129.6 Grams per liter (g/L) | Standard Deviation 6.5 |
| FF 100 µg | Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Values at Day 14 of the Respective Treatment Period | MCHC, n=23, 21 | 336.6 Grams per liter (g/L) | Standard Deviation 7.8 |
Primary
Mean Corpuscle Hemoglobin (MCH) Values at Day 14 of the Respective Treatment Period
Blood samples were collected for the measurement of MCH at Day 14 of the respective treatment period.
Time frame: Day 14 of the respective treatment period (up to Study Day 44)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Corpuscle Hemoglobin (MCH) Values at Day 14 of the Respective Treatment Period | 29.18 10^12 picograms (pg) per cell | Standard Deviation 1.279 |
| FF 100 µg | Mean Corpuscle Hemoglobin (MCH) Values at Day 14 of the Respective Treatment Period | 29.24 10^12 picograms (pg) per cell | Standard Deviation 1.458 |
Primary
Mean Corpuscle Volume (MCV) Value at Day 14 of the Respective Treatment Period
Blood samples were collected for the measurement of MCV at Day 14 of the respective treatment period.
Time frame: Day 14 of the respective treatment period (up to Study Day 44)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed .
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Corpuscle Volume (MCV) Value at Day 14 of the Respective Treatment Period | 86.8 10^15 femtoliters (fL) per cell | Standard Deviation 4.05 |
| FF 100 µg | Mean Corpuscle Volume (MCV) Value at Day 14 of the Respective Treatment Period | 86.9 10^15 femtoliters (fL) per cell | Standard Deviation 4.4 |
Primary
Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in deciding whether reporting is appropriate in other situations. Refer to the General Adverse AE/SAE module for a complete list of AEs and SAEs.
Time frame: From the start of study medication until Week 11 (Visit 6)/Early Withdrawal
Population: All Subjects Population: all participants who received at least one dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period | Any AE | 4 participants |
| Placebo | Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period | Any SAE | 0 participants |
| FF 100 µg | Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period | Any AE | 8 participants |
| FF 100 µg | Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period | Any SAE | 0 participants |
Primary
Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period
Peak Expiratory Flow (PEF) is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF is calculated as the maximum of three readings taken at each timepoint for each participant. Baseline is defined as the maximum pre-dose measurement at Day 1 for each period.
Time frame: Day 1 and Day 14 of the respective treatment period (up to Study Day 44)
Population: All Subjects Population, Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 1, Baseline, n=25, 25 | 242.3 liters/minute | Standard Deviation 77.68 |
| Placebo | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 1, 15 minutes post-dose, n=25, 25 | 242.1 liters/minute | Standard Deviation 78.98 |
| Placebo | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 1, 30 minutes post-dose, n=25, 25 | 249.2 liters/minute | Standard Deviation 78.07 |
| Placebo | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 1, 1 hour post-dose, n=25, 25 | 247.7 liters/minute | Standard Deviation 72.54 |
| Placebo | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 1, 2 hours post-dose, n=25, 25 | 252.3 liters/minute | Standard Deviation 89.08 |
| Placebo | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, Pre-dose, n=24, 23 | 242.0 liters/minute | Standard Deviation 73.6 |
| Placebo | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, 30 minutes post-dose, n=23, 23 | 246.1 liters/minute | Standard Deviation 81.17 |
| Placebo | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, 1 hours post-dose, n=23, 23 | 247.0 liters/minute | Standard Deviation 77.95 |
| Placebo | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, 2 hours post-dose, n=23, 23 | 249.5 liters/minute | Standard Deviation 74.09 |
| Placebo | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, 4 hours post-dose, n=23, 23 | 250.6 liters/minute | Standard Deviation 82.43 |
| Placebo | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, 7 hours post-dose, n=23, 23 | 246.3 liters/minute | Standard Deviation 79.07 |
| Placebo | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, 12 hours post-dose, n=23, 23 | 241.9 liters/minute | Standard Deviation 75.8 |
| FF 100 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, 7 hours post-dose, n=23, 23 | 232.1 liters/minute | Standard Deviation 59.82 |
| FF 100 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 1, Baseline, n=25, 25 | 238.4 liters/minute | Standard Deviation 64.98 |
| FF 100 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, 30 minutes post-dose, n=23, 23 | 238.8 liters/minute | Standard Deviation 88.78 |
| FF 100 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 1, 15 minutes post-dose, n=25, 25 | 238.2 liters/minute | Standard Deviation 58.97 |
| FF 100 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, 4 hours post-dose, n=23, 23 | 246.2 liters/minute | Standard Deviation 70.43 |
| FF 100 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 1, 30 minutes post-dose, n=25, 25 | 246.0 liters/minute | Standard Deviation 62.65 |
| FF 100 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, 1 hours post-dose, n=23, 23 | 237.6 liters/minute | Standard Deviation 78.66 |
| FF 100 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 1, 1 hour post-dose, n=25, 25 | 247.0 liters/minute | Standard Deviation 64.75 |
| FF 100 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, 12 hours post-dose, n=23, 23 | 245.6 liters/minute | Standard Deviation 76.68 |
| FF 100 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 1, 2 hours post-dose, n=25, 25 | 252.6 liters/minute | Standard Deviation 61.77 |
| FF 100 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, 2 hours post-dose, n=23, 23 | 242.3 liters/minute | Standard Deviation 72.02 |
| FF 100 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, Pre-dose, n=24, 23 | 240.6 liters/minute | Standard Deviation 83.88 |
Primary
Reticulocyte and Red Blood Cell (RBC) Values at Day 14 of the Respective Treatment Period
Blood samples were collected for the measurement of reticulocyte and RBCs at Day 14 of the respective treatment period.
Time frame: Day 14 of the respective treatment period (up to Study Day 44)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Reticulocyte and Red Blood Cell (RBC) Values at Day 14 of the Respective Treatment Period | Reticulocytes, n=23, 21 | 0.04952 10^12 cells per liter (TI/L) | Standard Deviation 0.024497 |
| Placebo | Reticulocyte and Red Blood Cell (RBC) Values at Day 14 of the Respective Treatment Period | RBCs, n=23, 21 | 4.43 10^12 cells per liter (TI/L) | Standard Deviation 0.277 |
| FF 100 µg | Reticulocyte and Red Blood Cell (RBC) Values at Day 14 of the Respective Treatment Period | Reticulocytes, n=23, 21 | 0.04499 10^12 cells per liter (TI/L) | Standard Deviation 0.021309 |
| FF 100 µg | Reticulocyte and Red Blood Cell (RBC) Values at Day 14 of the Respective Treatment Period | RBCs, n=23, 21 | 4.46 10^12 cells per liter (TI/L) | Standard Deviation 0.296 |
Primary
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period
SBP and DBP were measured at Baseline and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1 for each period.
Time frame: Baseline and Day 14 of the respective treatment period (up to Study Day 44)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 1 DBP, Predose, n=25, 26 | 62.0 Millimeters of mercury (mmHg) | Standard Deviation 9.71 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 1 SBP, 30 minutes, n=25, 26 | 101.2 Millimeters of mercury (mmHg) | Standard Deviation 8.57 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 1 DBP, 30 minutes, n=25, 26 | 63.0 Millimeters of mercury (mmHg) | Standard Deviation 9.09 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 SBP, 1 hour, n=23, 23 | 102.6 Millimeters of mercury (mmHg) | Standard Deviation 9.14 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 1 DBP, 1 hour, n=25, 26 | 61.4 Millimeters of mercury (mmHg) | Standard Deviation 8.69 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 1 SBP, Predose, n=25, 26 | 103.1 Millimeters of mercury (mmHg) | Standard Deviation 9.29 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 1 DBP, 2 hours, n=25, 26 | 63.0 Millimeters of mercury (mmHg) | Standard Deviation 8.34 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 SBP, 4 hours, n=23, 23 | 102.0 Millimeters of mercury (mmHg) | Standard Deviation 9.07 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 DBP, Predose, n=24, 23 | 61.3 Millimeters of mercury (mmHg) | Standard Deviation 6.91 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 1 SBP, 2 hours, n=25, 26 | 102.9 Millimeters of mercury (mmHg) | Standard Deviation 9.98 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 DBP, 1 hour, n=23, 23 | 63.9 Millimeters of mercury (mmHg) | Standard Deviation 10.14 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 SBP, 7 hours, n=23, 23 | 103.4 Millimeters of mercury (mmHg) | Standard Deviation 9.34 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 DBP, 4 hours, n=23, 23 | 60.4 Millimeters of mercury (mmHg) | Standard Deviation 8.81 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 1 SBP, 1 hour, n=25, 26 | 102.7 Millimeters of mercury (mmHg) | Standard Deviation 11.11 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 DBP, 7 hours, n=23, 23 | 61.8 Millimeters of mercury (mmHg) | Standard Deviation 9.27 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 SBP, 12 hours, n=23, 23 | 103.2 Millimeters of mercury (mmHg) | Standard Deviation 7.42 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 DBP, 12 hours, n=23, 23 | 62.0 Millimeters of mercury (mmHg) | Standard Deviation 8.1 |
| Placebo | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 SBP, Predose, n=24, 23 | 101.8 Millimeters of mercury (mmHg) | Standard Deviation 8.04 |
| FF 100 µg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 DBP, 12 hours, n=23, 23 | 63.9 Millimeters of mercury (mmHg) | Standard Deviation 8.68 |
| FF 100 µg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 1 SBP, Predose, n=25, 26 | 102.9 Millimeters of mercury (mmHg) | Standard Deviation 9.68 |
| FF 100 µg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 1 SBP, 1 hour, n=25, 26 | 105.2 Millimeters of mercury (mmHg) | Standard Deviation 11.19 |
| FF 100 µg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 1 SBP, 2 hours, n=25, 26 | 103.9 Millimeters of mercury (mmHg) | Standard Deviation 9.04 |
| FF 100 µg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 SBP, Predose, n=24, 23 | 102.1 Millimeters of mercury (mmHg) | Standard Deviation 9.92 |
| FF 100 µg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 SBP, 1 hour, n=23, 23 | 103.1 Millimeters of mercury (mmHg) | Standard Deviation 8.04 |
| FF 100 µg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 SBP, 4 hours, n=23, 23 | 102.7 Millimeters of mercury (mmHg) | Standard Deviation 9.43 |
| FF 100 µg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 SBP, 7 hours, n=23, 23 | 103.9 Millimeters of mercury (mmHg) | Standard Deviation 9.88 |
| FF 100 µg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 SBP, 12 hours, n=23, 23 | 106.3 Millimeters of mercury (mmHg) | Standard Deviation 10.61 |
| FF 100 µg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 1 DBP, Predose, n=25, 26 | 61.7 Millimeters of mercury (mmHg) | Standard Deviation 7.66 |
| FF 100 µg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 1 DBP, 30 minutes, n=25, 26 | 62.6 Millimeters of mercury (mmHg) | Standard Deviation 6.39 |
| FF 100 µg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 1 DBP, 1 hour, n=25, 26 | 62.3 Millimeters of mercury (mmHg) | Standard Deviation 8.73 |
| FF 100 µg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 1 DBP, 2 hours, n=25, 26 | 61.2 Millimeters of mercury (mmHg) | Standard Deviation 8.39 |
| FF 100 µg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 DBP, Predose, n=24, 23 | 61.4 Millimeters of mercury (mmHg) | Standard Deviation 6.81 |
| FF 100 µg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 DBP, 1 hour, n=23, 23 | 62.7 Millimeters of mercury (mmHg) | Standard Deviation 6.88 |
| FF 100 µg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 DBP, 4 hours, n=23, 23 | 60.5 Millimeters of mercury (mmHg) | Standard Deviation 6.73 |
| FF 100 µg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 14 DBP, 7 hours, n=23, 23 | 62.3 Millimeters of mercury (mmHg) | Standard Deviation 8.23 |
| FF 100 µg | Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period | Day 1 SBP, 30 minutes, n=25, 26 | 103.8 Millimeters of mercury (mmHg) | Standard Deviation 10.44 |
Primary
Total Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period
Blood samples were collected for the measurement of total bilirubin, creatinine, and uric acid at Day 14 of the respective treatment period.
Time frame: Day 14 of the respective treatment period (up to Study Day 44)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Total Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period | Total bilirubin, n= 22, 20 | 5.9 Micromoles per liter (µmol/L) | Standard Deviation 2.27 |
| Placebo | Total Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period | Creatinine, n= 22, 20 | 39.89 Micromoles per liter (µmol/L) | Standard Deviation 7.775 |
| Placebo | Total Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period | Uric acid, n= 22, 20 | 237.7 Micromoles per liter (µmol/L) | Standard Deviation 65.46 |
| FF 100 µg | Total Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period | Uric acid, n= 22, 20 | 234.5 Micromoles per liter (µmol/L) | Standard Deviation 70.97 |
| FF 100 µg | Total Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period | Total bilirubin, n= 22, 20 | 5.6 Micromoles per liter (µmol/L) | Standard Deviation 1.23 |
| FF 100 µg | Total Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period | Creatinine, n= 22, 20 | 40.62 Micromoles per liter (µmol/L) | Standard Deviation 8.421 |
Secondary
AUC(0-t) on Day 14 of the Respective Treatment Period
Area under the concentration-time (AUC(0-t)) curve from time zero (pre-dose) to the last time of quantifiable concentration of FF on Day 14 of the respective treatment period was measured. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period. Due to non-quantifiable values, it was not possible to derive AUC(0-12).
Time frame: Day 14 of the respective treatment period
Population: Pharmacokinetic (PK) Population: all participants in the All Subjects Population for whom a PK sample was obtained and analyzed
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| FF 100 µg | AUC(0-t) on Day 14 of the Respective Treatment Period | 91.29 picograms*hour per milliliter (pg*hr/mL) |
Secondary
Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Days 1 and 14 of the Respective Treatment Period
During the inhalation profile assessment, participants inhaled through a mouthpiece from a device with a similar resistance to the dry powder inhaler used for this study. Average flow rate is defined as the average inspiratory flow rate (Liters \[L\]/min) across the inhalation profile when inhaling across the resistance of the inhaler. PIFR is defined as the Peak Inspiratory Flow Rate (L/min) of the inhalation profile when inhaling across the resistance of the inhaler.The pressure drop during the inhalation was measured, and the inhalation profiles (pressure drop versus time profile) of the participants were obtained. The mean of the two inhalation profile measurements was used for each day (Days 1 and 14 of the respective treatment period), and the average flow rate and PIFR were determined.
Time frame: Day 1 and Day 14 of the respective treatment period
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Days 1 and 14 of the Respective Treatment Period | Day 1 PIFR, n=21, 20 | 51.83 Liters per minute (L/min) | Standard Deviation 17.286 |
| Placebo | Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Days 1 and 14 of the Respective Treatment Period | Day 1 Average flow rate, n=21, 20 | 35.38 Liters per minute (L/min) | Standard Deviation 11.441 |
| Placebo | Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Days 1 and 14 of the Respective Treatment Period | Day 14 PIFR, n=21, 22 | 55.70 Liters per minute (L/min) | Standard Deviation 16.589 |
| Placebo | Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Days 1 and 14 of the Respective Treatment Period | Day 14 Average flow rate, n=21, 22 | 36.25 Liters per minute (L/min) | Standard Deviation 11.243 |
| FF 100 µg | Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Days 1 and 14 of the Respective Treatment Period | Day 14 PIFR, n=21, 22 | 54.76 Liters per minute (L/min) | Standard Deviation 17.986 |
| FF 100 µg | Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Days 1 and 14 of the Respective Treatment Period | Day 1 Average flow rate, n=21, 20 | 34.65 Liters per minute (L/min) | Standard Deviation 10.84 |
| FF 100 µg | Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Days 1 and 14 of the Respective Treatment Period | Day 1 PIFR, n=21, 20 | 52.90 Liters per minute (L/min) | Standard Deviation 16.028 |
| FF 100 µg | Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Days 1 and 14 of the Respective Treatment Period | Day 14 Average flow rate, n=21, 22 | 36.17 Liters per minute (L/min) | Standard Deviation 12.772 |
Secondary
Average Oropharyngeal Cross-sectional Area on Days 1 and 14 of the Respective Treatment Period
During the pharyngometry assessment, participants inhaled through a wavetube, which had a mouthpiece with the same dimensions as the mouthpiece on the dry powder inhaler used for this study. This technique was used to measure the size of the throat and mouth (oropharynx) in the form of pharyngograms. Pharyngometry data were recorded for each day (Days 1 and 14 of the respective treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated.
Time frame: Days 1 and 14 of the respective treatment period
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Average Oropharyngeal Cross-sectional Area on Days 1 and 14 of the Respective Treatment Period | Day 1, n=14, 18 | 4.06 centimeters squared (cm^2) | Standard Deviation 1.875 |
| Placebo | Average Oropharyngeal Cross-sectional Area on Days 1 and 14 of the Respective Treatment Period | Day 14, n= 12, 12 | 5.49 centimeters squared (cm^2) | Standard Deviation 1.586 |
| FF 100 µg | Average Oropharyngeal Cross-sectional Area on Days 1 and 14 of the Respective Treatment Period | Day 1, n=14, 18 | 4.24 centimeters squared (cm^2) | Standard Deviation 1.677 |
| FF 100 µg | Average Oropharyngeal Cross-sectional Area on Days 1 and 14 of the Respective Treatment Period | Day 14, n= 12, 12 | 4.58 centimeters squared (cm^2) | Standard Deviation 1.497 |
Secondary
Cmax on Day 14 of the Respective Treatment Period
Cmax is defined as the maximum observed concentration on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period.
Time frame: Day 14 of the respective treatment period
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| FF 100 µg | Cmax on Day 14 of the Respective Treatment Period | 24.68 picograms per milliliter (pg/mL) |
Secondary
Distance of Assessment on Days 1 and 14 of the Respective Treatment Period
During the pharyngometry assessment, participants inhaled through a wavetube, which had a mouthpiece with the same dimensions as the mouthpiece on the dry powder inhaler used for this study. This technique was used to measure the size of the throat and mouth (oropharynx) in the form of pharyngograms. Distance of assessment is defined as the distance (length measured in centimeters \[cm\]) estimated to be from the lips to the larynx. Pharyngometry data were recorded for each day (Days 1 and 14 of each treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated.
Time frame: Days 1 and 14 of the respective treatment period
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Distance of Assessment on Days 1 and 14 of the Respective Treatment Period | Day 1, n=14, 18 | 18.63 centimeters (cm) | Standard Deviation 1.736 |
| Placebo | Distance of Assessment on Days 1 and 14 of the Respective Treatment Period | Day 14, n= 12, 12 | 19.37 centimeters (cm) | Standard Deviation 1.823 |
| FF 100 µg | Distance of Assessment on Days 1 and 14 of the Respective Treatment Period | Day 1, n=14, 18 | 18.69 centimeters (cm) | Standard Deviation 1.432 |
| FF 100 µg | Distance of Assessment on Days 1 and 14 of the Respective Treatment Period | Day 14, n= 12, 12 | 18.61 centimeters (cm) | Standard Deviation 1.942 |
Secondary
Ex-throat Dose (ETD) and ETD <2 Microns on Days 1 and 14 of the Respective Treatment Period
The ex-throat dose (ETD) and the nominal ETD is the mass (micrograms) of active investigational material that passes beyond the throat, nominal being the mean.The recorded inhalation profiles of the participants and the mouth-throat (oropharyngeal) models of the sizes that approximated to pharyngometry measurements of the participants were used in conjunction with the electronic Lung (eLung) for in vitro assessment. The eLung is a breathing simulator that replicates the selected inhalation profile with an active inhaler placed at the lips end of the selected ororpharyngeal model. After the dose is emitted from the inhaler, the analysis and assay of throat deposition and material passing beyond the throat was used to derive the nominal, minimum, and maximum predicted ETD and ETD \<2 microns.
Time frame: Day 1 and Day 14 of the respective treatment period
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Days 1 and 14 of the Respective Treatment Period | Day 1, Nominal ETD, n=0, 17 | 29.37 micrograms | Standard Deviation 2.874 |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Days 1 and 14 of the Respective Treatment Period | Day 14, Nominal ETD, n=0, 12 | 29.83 micrograms | Standard Deviation 2.528 |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Days 1 and 14 of the Respective Treatment Period | Day 1, Minimum ETD, n=0, 17 | 28.47 micrograms | Standard Deviation 3.241 |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Days 1 and 14 of the Respective Treatment Period | Day 14, Minimum ETD, n=0, 12 | 29.35 micrograms | Standard Deviation 2.664 |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Days 1 and 14 of the Respective Treatment Period | Day 1, Maximum ETD, n=0, 17 | 30.26 micrograms | Standard Deviation 2.598 |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Days 1 and 14 of the Respective Treatment Period | Day 14, Maximum ETD, n=0, 12 | 30.26 micrograms | Standard Deviation 2.472 |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Days 1 and 14 of the Respective Treatment Period | Day 1, ETD <2 microns, n=0, 17 | 5.13 micrograms | Standard Deviation 0.498 |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Days 1 and 14 of the Respective Treatment Period | Day 14, ETD <2 microns, n=0, 12 | 5.07 micrograms | Standard Deviation 0.455 |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Days 1 and 14 of the Respective Treatment Period | Day 1, Minimum ETD <2 microns, n=0, 17 | 4.96 micrograms | Standard Deviation 0.459 |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Days 1 and 14 of the Respective Treatment Period | Day 14, Minimum ETD <2 microns, n=0, 12 | 4.99 micrograms | Standard Deviation 0.448 |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Days 1 and 14 of the Respective Treatment Period | Day 1, Maximum ETD <2 microns, n=0, 17 | 5.30 micrograms | Standard Deviation 0.559 |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Days 1 and 14 of the Respective Treatment Period | Day 14, Maximum ETD <2 microns, n=0, 12 | 5.17 micrograms | Standard Deviation 0.476 |
Secondary
Inhalation Time on Days 1 and 14 of the Respective Treatment Period
During the inhalation profile assessment, participants inhaled through a mouthpiece from a device with a similar resistance to the dry powder inhaler used for this study. Inhalation time is defined as the duration of the inhalation(s) when inhaling across the resistance of the inhaler. The pressure drop during the inhalation was measured, and the inhalation profiles (pressure drop versus time profile) of the participants were obtained. The mean of the two inhalation profile measurements was used for each day (Days 1 and 14 of the respective treatment period), and the inhalation time was determined.
Time frame: Day 1 and Day 14 of the respective treatment period
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Inhalation Time on Days 1 and 14 of the Respective Treatment Period | Day 1, n=21, 20 | 1.71 Seconds | Standard Deviation 0.534 |
| Placebo | Inhalation Time on Days 1 and 14 of the Respective Treatment Period | Day 14, n= 21, 22 | 1.60 Seconds | Standard Deviation 0.802 |
| FF 100 µg | Inhalation Time on Days 1 and 14 of the Respective Treatment Period | Day 1, n=21, 20 | 1.93 Seconds | Standard Deviation 0.861 |
| FF 100 µg | Inhalation Time on Days 1 and 14 of the Respective Treatment Period | Day 14, n= 21, 22 | 1.61 Seconds | Standard Deviation 0.858 |
Secondary
Inhaled Volume on Days 1 and 14 of the Respective Treatment Period
During the inhalation profile assessment, participants inhaled through a mouthpiece from a device with a similar resistance to the dry powder inhaler used for this study. Inhaled volume is defined as the volume of air (Liters) inhaled during the inhalation across the resistance of the inhaler. The pressure drop during the inhalation was measured, and the inhalation profiles (pressure drop versus time profile) of the participants were obtained. The mean of the two inhalation profile measurements was used for each day (Days 1 and 14 of the respective treatment period), and the inhalaled volume was determined.
Time frame: Day 1 and Day 14 of the respective treatment period
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Inhaled Volume on Days 1 and 14 of the Respective Treatment Period | Day 1, n=21, 20 | 0.99 Liters | Standard Deviation 0.461 |
| Placebo | Inhaled Volume on Days 1 and 14 of the Respective Treatment Period | Day 14, n= 21, 22 | 1.00 Liters | Standard Deviation 0.58 |
| FF 100 µg | Inhaled Volume on Days 1 and 14 of the Respective Treatment Period | Day 1, n=21, 20 | 1.07 Liters | Standard Deviation 0.48 |
| FF 100 µg | Inhaled Volume on Days 1 and 14 of the Respective Treatment Period | Day 14, n= 21, 22 | 0.95 Liters | Standard Deviation 0.541 |
Secondary
Oropharyngeal Volume on Days 1 and 14 of the Respective Treatment Period
During the pharyngometry assessment, participants inhaled through a wavetube, which had a mouthpiece with the same dimensions as the mouthpiece on the dry powder inhaler used for this study. This technique was used to measure the size of the throat and mouth (oropharynx) in the form of pharyngograms. Oropharyngeal volume is defined as the volume (cm\^3) of the mouth and throat estimated to be from the lips to the larynx. Pharyngometry data were recorded for each day (Days 1 and 14 of the respective treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated.
Time frame: Days 1 and 14 of the respective treatment period
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Oropharyngeal Volume on Days 1 and 14 of the Respective Treatment Period | Day 1, n=14, 18 | 74.19 cubic centimeters (cm^3) | Standard Deviation 32.402 |
| Placebo | Oropharyngeal Volume on Days 1 and 14 of the Respective Treatment Period | Day 14, n= 12, 12 | 106.31 cubic centimeters (cm^3) | Standard Deviation 33.188 |
| FF 100 µg | Oropharyngeal Volume on Days 1 and 14 of the Respective Treatment Period | Day 14, n= 12, 12 | 86.22 cubic centimeters (cm^3) | Standard Deviation 34.363 |
| FF 100 µg | Oropharyngeal Volume on Days 1 and 14 of the Respective Treatment Period | Day 1, n=14, 18 | 78.86 cubic centimeters (cm^3) | Standard Deviation 31.092 |
Secondary
Peak Pressure Drop on Days 1 and 14 of the Respective Treatment Period
During the inhalation profile assessment, participants inhaled through a mouthpiece from a device with a similar resistance to the dry powder inhaler used for this study. Peak pressure drop is defined as the maximum pressure drop (kilopascal \[kPa\]) achieved during inhalation across the resistance of the inhaler. The pressure drop during the inhalation was measured, and the inhalation profiles (pressure drop versus time profile) of the participants were obtained. The mean of the two inhalation profile measurements was calculated for each day (Days 1 and 14 of the respective treatment period), and used for subsequent modeling and prediction of dose emission attributes.
Time frame: Day 1 and Day 14 of the respective treatment period
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Peak Pressure Drop on Days 1 and 14 of the Respective Treatment Period | Day 1, n=21, 20 | 2.44 Kilopascal (kpa) | Standard Deviation 1.63 |
| Placebo | Peak Pressure Drop on Days 1 and 14 of the Respective Treatment Period | Day 14, n= 21, 22 | 2.78 Kilopascal (kpa) | Standard Deviation 1.543 |
| FF 100 µg | Peak Pressure Drop on Days 1 and 14 of the Respective Treatment Period | Day 1, n=21, 20 | 2.53 Kilopascal (kpa) | Standard Deviation 1.56 |
| FF 100 µg | Peak Pressure Drop on Days 1 and 14 of the Respective Treatment Period | Day 14, n= 21, 22 | 2.74 Kilopascal (kpa) | Standard Deviation 1.609 |
Secondary
Serum Cortisol Weighted Mean (0-12 Hours) on Day 14 of the Respective Treatment Period
Serum cortisol weighted mean was determined for each participant over the time period 0-12 hours on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period.
Time frame: Day 14 of the respective treatment period
Population: All Subjects Population. Only those participants available at the specified time point were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Serum Cortisol Weighted Mean (0-12 Hours) on Day 14 of the Respective Treatment Period | 178.76 nanomoles per Liter |
| FF 100 µg | Serum Cortisol Weighted Mean (0-12 Hours) on Day 14 of the Respective Treatment Period | 150.41 nanomoles per Liter |
Secondary
Tmax and t at Day 14 of the Respective Treatment Period
tmax is defined as the time to reach the observed maximum concentration, and t is defined as the time of the last observed quantifiable concentration on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period.
Time frame: Day 14 of the respective treatment period
Population: PK Population. Only those participant who had quantifiable FF concentrations were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FF 100 µg | Tmax and t at Day 14 of the Respective Treatment Period | tmax | 0.863 hours | Standard Deviation 0.7926 |
| FF 100 µg | Tmax and t at Day 14 of the Respective Treatment Period | t | 6.953 hours | Standard Deviation 4.0875 |
Secondary
Total Emitted Dose (TED) on Days 1 and 14 of the Respective Treatment Period
The total emitted dose (TED) is defined as the mass (micrograms) of the nominal dose that passes beyond the throat. The recorded inhalation profiles of the participants and the mouth-throat (oropharyngeal) models of the sizes that approximated to pharyngometry measurements of the participants were used in conjunction with the electronic Lung (eLung) for in vitro assessment. The eLung is a breathing simulator that replicates the selected inhalation profile with an active inhaler placed at the lips end of the selected ororpharyngeal model. After the dose is emitted from the inhaler, the analysis and assay of throat deposition and material passing beyond the throat was used to derive the nominal, minimum, and maximum predicted total emitted dose.
Time frame: Day 1 and Day 14 of the respective treatment period
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FF 100 µg | Total Emitted Dose (TED) on Days 1 and 14 of the Respective Treatment Period | Day 1, Minimum TED, n=0, 20 | 84.84 micrograms | Standard Deviation 1.617 |
| FF 100 µg | Total Emitted Dose (TED) on Days 1 and 14 of the Respective Treatment Period | Day 1, Nominal TED, n=0, 20 | 85.35 micrograms | Standard Deviation 1.576 |
| FF 100 µg | Total Emitted Dose (TED) on Days 1 and 14 of the Respective Treatment Period | Day 14, Nominal TED, n=0, 22 | 85.57 micrograms | Standard Deviation 1.857 |
| FF 100 µg | Total Emitted Dose (TED) on Days 1 and 14 of the Respective Treatment Period | Day 14, Minimum TED, n=0, 22 | 85.17 micrograms | Standard Deviation 1.905 |
| FF 100 µg | Total Emitted Dose (TED) on Days 1 and 14 of the Respective Treatment Period | Day 1, Maximum TED, n=0, 20 | 85.86 micrograms | Standard Deviation 1.639 |
| FF 100 µg | Total Emitted Dose (TED) on Days 1 and 14 of the Respective Treatment Period | Day 14, Maximum TED, n=0, 22 | 85.97 micrograms | Standard Deviation 1.861 |