Asthma
Conditions
Keywords
pediatric ages 5 to 11 years
Brief summary
This study will investigate the safety and tolerability, pharmacokinetics, and pharmacodynamics of fluticasone furoate/vilanterol (FF/VI) 100/25mcg administered using the novel dry powder inhaler in children aged 5 to 11 years with persistent asthma.
Detailed description
This study will investigate the safety and tolerability, pharmacokinetics, and pharmacodynamics of fluticasone furoate/vilanterol (FF/VI) 100/25mcg administered using the novel dry powder inhaler in children aged 5 to 11 years with persistent asthma. Fluticasone furoate (FF, GW685698) is a novel once daily inhaled corticosteroid (ICS) and vilanterol (VI, GW642444) is an inhaled once daily long-acting beta2 agonist (LABA). FF/VI is a novel ICS/LABA combination with once-daily dosing being developed for the treatment of asthma in adults, adolescents, and children of 5 years and above. This study will be a randomized, double-blind, repeat dose, two period crossover study, with FF as the control. During each of two treatment periods subjects will receive either FF/VI 100/25 micrograms (mcg) or FF 100 mcg daily on 14 consecutive mornings via the novel dry powder inhaler. Approximately 26 subjects will be recruited into this study, with a target of 20 completed subjects. Safety, tolerability, pharmacokinetics and glucose , potassium and cortisol levels will be investigated.
Interventions
DRUGFluticasone Furoate
100mcg delivered via a novel dry powder inhaler on days 1-14 of one study treatment period.
100/25 mcg delivered via a novel dry powder inhaler on days 1-14 of one study treatment period.
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
* Healthy as determined by a study physician, based medical history, physical examination, laboratory testing, and electrocardiogram (ECG); with no significant medical condition apart from asthma, eczema, or rhinitis. A subject with a clinical abnormality or laboratory parameters outside the reference range for this study may be included if the Investigator and GSK Medical Monitor agree the finding is unlikely to introduce additional risk factors or interfere with the study procedures. * Male and pre-menarchial female subjects aged 5 to less than 12 years on the last planned treatment day are eligible for this study. Pre-menarchial females are defined as any female who has not begun menses and is considered Tanner Stage 2 or less. * Diagnosis of asthma at least 6 months prior to screening. * Stable asthma therapy (fluticasone propionate, total daily dose less than or equal to 400 microgram or equivalent) and short acting beta-agonist (SABA) inhaler for at least 4 weeks prior to screening. * Subjects must be controlled on their existing asthma treatment at screening, which will be continued during the run-in, washout and run-out periods (but not during active treatment periods). Control is defined as a Childhood Asthma Control Test score of \>19 and (Peak Expiratory Flow) PEF more than 75 percent predicted. * Subjects must demonstrate an ability to accept and effectively use a demonstration inhaler from the demonstration kits provided. * Subjects must weigh at least 20 kilograms. * The subject and parent/guardian are able to understand and comply with protocol requirements, instructions, and protocol stated restrictions. The parent or guardian must have the ability to read, write, and record diary information collected throughout the study. The parent or guardian must have the ability to manage study drug administration and PEF assessments. * At least one parent/guardian has signed and dated the written informed consent prior to admission to the study. This will be accompanied by informed assent from the subject for children aged 7 to 11 years.
Exclusion criteria
* Subjects with a history of life-threatening asthma, an asthma exacerbation requiring systemic corticosteroids or Emergency Room attendance (within 3 months) or requiring hospitalization (within 6 months) prior to screening. * Subjects with any medical condition or circumstance making the volunteer unsuitable for participation in the study. * Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus, or middle ear, not resolved within 4 weeks of screening leading to a change in asthma management; or, in the opinion of the investigator, is likely to affect the subject's asthma status or ability to participate in the study. * Clinical visual evidence of oral candidiasis at screening. * Subjects currently receiving (or have received within 4 weeks of screening) asthma therapies including theophyllines, long-acting inhaled beta-agonists, oral beta-agonists, or who have changed their asthma medication within 4 weeks of screening. * Significant abnormality of rate, interval, conduction or rhythm in the 12-lead ECG (electrocardiogram), determined by the investigator in conjunction with the age and gender of the child and the assessment provided by the remote analysis service. * QTcF (QT interval corrected for heart rate using Fridericia's formula) more than 450 milliseconds or an ECG not suitable for QT measurement (e.g. poorly defined termination of the T wave). * Aspartarte aminotransferase, Alanine aminotransferase, alkaline phosphatase and bilirubin more than 1.5 times Upper Limit of Normal (ULN) (isolated bilirubin more than 1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35 percent). * A known or suspected sensitivity to any constituents of the novel dry powder inhaler (i.e. lactose or magnesium stearate) (e.g. history of severe milk protein allergy) * Any adverse reaction including immediate or delayed hypersensitivity to any beta-2-agonist, sympathomimetic drug, or any intranasal, inhaled or systemic corticosteroid therapy. * Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. * Consumption of red wine, seville oranges, grapefruit or grapefruit juice, and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication. * The subject has participated in a clinical trial and has received an investigational product within 30 days, 5 half-lives, or twice the duration of the biological effect of the investigational product (whichever is longer). * Exposure to more than four new chemical entities within 12 months prior to the first dosing day. * Where participation in the study would result in donation of blood or blood products in excess of the lesser of 50 millilitres (mL) or 3mL per kilogram within a 56 day period. * Parent/guardian has a 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. * Unwillingness or inability of the subject or parent/guardian to follow the procedures outlined in the protocol. * Subject who is mentally or legally incapacitated. * Children who are wards of the state or government. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 9)/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. |
| 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 63) | 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 63) | 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 63) | Blood samples were collected for the measurement of reticulocytes 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 63) | 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 63) | 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 63) | 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 63) | 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 63) | 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 63) | 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, Direct 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 63) | Blood samples were collected for the measurement of total bilirubin, direct 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 63) | 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. |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 1 and Day 14 of the respective treatment period (up to Study Day 63) | SBP and DBP were measured at Day 1 and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1. Change from Baseline was calculated as the Day 14 value minus the Baseline value. |
| Change From Baseline in Heart Rate at Day1 and Day 14 of the Respective Treatment Period | Day 1 and Day 14 of the respective treatment period (up to Study Day 63) | Heart rate (HR) was measured at Day 1 and Day 14 of the respective treatment period. hr=hour. Baseline is defined as the pre-dose measurement at Day 1. Change from Baseline was calculated as the Day 14 value minus the Baseline value. Treatment, period, day (1 and 14), participant Baseline, period Baseline, and treatment\*day interaction were fitted as fixed effects, and participant was fitted as a random effect. |
| Maximum QTcF at Day 1 and Day 14 of the Respective Treatment Period | Day 1 and Day 14 of the respective treatment period (up to Study Day 63) | QTcF is the QT domain corrected for heart rate by Fridericia's formula. Treatment, period, day (1 and 14), participant Baseline, period Baseline, and treatment\*day interaction were fitted as fixed effects, and participant was fitted as a random effect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Emitted Dose (TED) on Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 63) | 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. |
| AUC(0-t) and AUC(0-4) of FF on Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 63) | Area under the concentration-time (AUC) curve from time zero (pre-dose) to the last time AUC(0-t) and from time zero to 4 hours AUC(0-4) of quantifiable concentration of FF on Day 14 of the respective treatment period was measured. Samples were collected at the following times: pre-dose; 10 minutes (min) and 30 min post-dose; and 1, 2, and 4 hours post-dose. 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 PK Population. |
| Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 63) | 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. |
| Cmax of FF on Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 63) | Cmax is defined as the maximum observed concentration of FF on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 10 minutes (min) and 30 min post-dose; and 1, 2, and 4 hours post-dose. |
| Tmax and Tlast of FF on Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 63) | tmax is defined as the time to reach the observed maximum concentration, and tlast 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; 10 minutes (min) and 30 min post-dose; and 1, 2, and 4 hours post-dose. |
| AUC(0-t) and AUC(0-4) of VI on Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 63) | Area under the concentration-time (AUC) curve from time zero (pre-dose) to the last time AUC(0-t) and from time zero to 4 hours AUC(0-4) of quantifiable concentration of VI on Day 14 of the respective treatment period was measured. Samples were collected at the following times: pre-dose; 10 minutes (min) and 30 min post-dose; and 1, 2, and 4 hours post-dose. 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 VI PK Population. |
| Cmax of VI on Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 63) | Cmax is defined as the maximum observed concentration of VI on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 10 minutes (min) and 30 min post-dose; and 1, 2, and 4 hours post-dose. |
| Tmax and Tlast of VI on Day 1 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 63) | tmax is defined as the time to reach the observed maximum VI concentration, and tlast is defined as the time of the last observed quantifiable VI concentration on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 10 minutes (min) and 30 min post-dose; and 1, 2, and 4 hours post-dose. |
| Blood Glucose and Potassium Values on Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 63) | Blood glucose and potassium values were measured on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 10 minutes (min) and 30 min post-dose; and 1, 2, and 4 hours post-dose. Weighted means were derived using the linear trapezoidal rule. Actual relative times were used for the calculation except where actual times were missing. If any actual times were missing, planned relative time were used for these observations. Treatment and period were fitted as fixed effects and participant was fitted as a random effect. |
| Serum Cortisol (SC) Weighted Mean (0-12 Hours) on Day 14 of the Respective Treatment Period | Day 14 of the respective treatment period (up to Study Day 63) | SC weighted mean was determined for each participant over the time period of 0-12 hours on Day 14 of the respective treatment period. SC weighted mean was derived by dividing the area under the concentration-time curve (AUC; defined as thearea under the concentration-time curve from time zero up to 24 hours) by the sample collection time interval. The sample collection time interval is defined as the difference between the time of the last cortisol sample and the time of the first cortisol sample. Samples were collected at the following time points: 0 (first blood draw/pre-dose); 2, 4, 8, and 12 hours (relative to the 0 time point). Weighted means were derived using the linear trapezoidal rule. Actual relative times were used for the calculation except where actual times were missing. If any actual times were missing, planned relative time were used for these observations. Treatment and period were fitted as fixed effects and participant was fitted as a random effect. |
| Average Oropharyngeal Cross-sectional Area 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 X) | 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 the 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 (Day 1 and Day 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 Day 1 and Day 14 of the Respective Treatment Period | Day 1 and Day 14 of the respective treatment period (up to Study Day 63) | 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 the respective treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated. |
| Oropharyngeal Volume 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 63) | 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 Day 1 and Day 14 of the Respective Treatment Period | Day 1 and Day 14 of the respective treatment period (up to Study Day 63) | 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 of the Respective Treatment Period | Day 1 and Day 14 of the respective treatment period (up to Study Day 63) | 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 (up to Study Day 63) | 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 (up to Study Day 63) | 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. |
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 treatments fluticasone furoate \[FF\] 100 µg/Vilanterol \[VI\] 25 µg.or FF 100 µg, followed by a cross over after a washout period of at least 7 days.
Participants by arm
| Arm | Count |
|---|---|
| FF 100 µg/VI 25 µg and FF 100 µg in TPs 1 and 2 All participants who received FF 100 µg/VI 25 µg in Treatment Period 1 and FF 100 µg in Treatment Period 2 or FF 100 µg in Treatment Period 1 and FF 100 µg/VI 25 µg in Treatment Period 2. The first 14-day treatment period was followed by a washout period of at least 7 days. Inhaled FF 100 µg/VI 25 µg and FF 100 µg were administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 2 | Protocol Violation | 0 | 1 |
| Treatment Period (TP) 1 | Met Protocol-defined Stopping Criteria | 0 | 1 |
| Treatment Period (TP) 1 | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | FF 100 µg/VI 25 µg and FF 100 µg in TPs 1 and 2 |
|---|---|
| Age, Continuous | 8.1 Years STANDARD_DEVIATION 1.97 |
| Gender Female | 11 Participants |
| Gender Male | 15 Participants |
| Race/Ethnicity, Customized African American/African Heritage | 3 Participants |
| Race/Ethnicity, Customized African American/African Heritage & White | 1 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 1 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 21 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 | 1 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 |
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 63)
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 |
|---|---|---|---|---|
| FF 100 µg/VI 25 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, 24 | 16.9 International units per liter (IU/L) | Standard Deviation 14.63 |
| FF 100 µg/VI 25 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, 24 | 278.4 International units per liter (IU/L) | Standard Deviation 110.01 |
| FF 100 µg/VI 25 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, 24 | 28.2 International units per liter (IU/L) | Standard Deviation 8.38 |
| FF 100 µg/VI 25 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, 24 | 14.6 International units per liter (IU/L) | Standard Deviation 7.74 |
| 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, 24 | 16.1 International units per liter (IU/L) | Standard Deviation 10.36 |
| 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, 24 | 17.7 International units per liter (IU/L) | Standard Deviation 14.88 |
| 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, 24 | 29.0 International units per liter (IU/L) | Standard Deviation 7.51 |
| 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, 24 | 272.6 International units per liter (IU/L) | Standard Deviation 119.48 |
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 63)
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 |
|---|---|---|---|---|
| FF 100 µg/VI 25 µg | Albumin and Total Protein Values at Day 14 of the Respective Treatment Period | Albumin, n=22, 24 | 45.5 Grams per liter | Standard Deviation 1.97 |
| FF 100 µg/VI 25 µg | Albumin and Total Protein Values at Day 14 of the Respective Treatment Period | Total protein, n=22, 24 | 70.4 Grams per liter | Standard Deviation 2.99 |
| FF 100 µg | Albumin and Total Protein Values at Day 14 of the Respective Treatment Period | Albumin, n=22, 24 | 45.6 Grams per liter | Standard Deviation 2.2 |
| FF 100 µg | Albumin and Total Protein Values at Day 14 of the Respective Treatment Period | Total protein, n=22, 24 | 70.4 Grams per liter | Standard Deviation 3.12 |
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 63)
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 |
|---|---|---|---|---|
| FF 100 µg/VI 25 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | Lymphocytes, n=21, 23 | 2.062 10^9 cells per liter (GI/L) | Standard Deviation 0.8462 |
| FF 100 µg/VI 25 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=21, 23 | 3.805 10^9 cells per liter (GI/L) | Standard Deviation 2.409 |
| FF 100 µg/VI 25 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | Eosinophils, n=21, 23 | 0.296 10^9 cells per liter (GI/L) | Standard Deviation 0.3395 |
| FF 100 µg/VI 25 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | Platelets, n=21, 23 | 270.5 10^9 cells per liter (GI/L) | Standard Deviation 92.27 |
| FF 100 µg/VI 25 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | Monocytes, n=21, 23 | 0.244 10^9 cells per liter (GI/L) | Standard Deviation 0.1188 |
| FF 100 µg/VI 25 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | WBC count, n=21, 23 | 6.43 10^9 cells per liter (GI/L) | Standard Deviation 2.889 |
| FF 100 µg/VI 25 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | Basophils, n=21, 23 | 0.025 10^9 cells per liter (GI/L) | Standard Deviation 0.0175 |
| FF 100 µg | Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period | WBC count, n=21, 23 | 5.98 10^9 cells per liter (GI/L) | Standard Deviation 1.897 |
| 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=21, 23 | 0.025 10^9 cells per liter (GI/L) | Standard Deviation 0.0153 |
| 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=21, 23 | 0.293 10^9 cells per liter (GI/L) | Standard Deviation 0.3957 |
| 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=21, 23 | 2.339 10^9 cells per liter (GI/L) | Standard Deviation 0.7391 |
| 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=21, 23 | 0.222 10^9 cells per liter (GI/L) | Standard Deviation 0.1375 |
| 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=21, 23 | 3.106 10^9 cells per liter (GI/L) | Standard Deviation 1.3526 |
| 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=21, 23 | 299.0 10^9 cells per liter (GI/L) | Standard Deviation 73.66 |
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 63)
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 |
|---|---|---|---|---|
| FF 100 µg/VI 25 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=22, 24 | 19.0 Millimoles per liter (mmol/L) | Standard Deviation 1.85 |
| FF 100 µg/VI 25 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=22, 24 | 4.24 Millimoles per liter (mmol/L) | Standard Deviation 0.184 |
| FF 100 µg/VI 25 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, 24 | 103.3 Millimoles per liter (mmol/L) | Standard Deviation 1.75 |
| FF 100 µg/VI 25 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, 24 | 138.6 Millimoles per liter (mmol/L) | Standard Deviation 1.84 |
| FF 100 µg/VI 25 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, 24 | 4.50 Millimoles per liter (mmol/L) | Standard Deviation 0.689 |
| FF 100 µg/VI 25 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, 24 | 4.52 Millimoles per liter (mmol/L) | Standard Deviation 1.006 |
| FF 100 µg/VI 25 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=22, 24 | 2.416 Millimoles per liter (mmol/L) | Standard Deviation 0.0591 |
| 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, 24 | 4.52 Millimoles per liter (mmol/L) | Standard Deviation 1.108 |
| 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=22, 24 | 2.415 Millimoles per liter (mmol/L) | Standard Deviation 0.0749 |
| 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, 24 | 103.8 Millimoles per liter (mmol/L) | Standard Deviation 1.79 |
| 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=22, 24 | 19.1 Millimoles per liter (mmol/L) | Standard Deviation 2.05 |
| 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, 24 | 4.53 Millimoles per liter (mmol/L) | Standard Deviation 0.523 |
| 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=22, 24 | 4.27 Millimoles per liter (mmol/L) | Standard Deviation 0.265 |
| 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, 24 | 139.0 Millimoles per liter (mmol/L) | Standard Deviation 1.85 |
Primary
Change From Baseline in Heart Rate at Day1 and Day 14 of the Respective Treatment Period
Heart rate (HR) was measured at Day 1 and Day 14 of the respective treatment period. hr=hour. Baseline is defined as the pre-dose measurement at Day 1. Change from Baseline was calculated as the Day 14 value minus the Baseline value. Treatment, period, day (1 and 14), participant Baseline, period Baseline, and treatment\*day interaction were fitted as fixed effects, and participant was fitted as a random effect.
Time frame: Day 1 and Day 14 of the respective treatment period (up to Study Day 63)
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 (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| FF 100 µg/VI 25 µg | Change From Baseline in Heart Rate at Day1 and Day 14 of the Respective Treatment Period | Day 1, n=25, 25 | 84.4 Beats per minute | Standard Error 1.63 |
| FF 100 µg/VI 25 µg | Change From Baseline in Heart Rate at Day1 and Day 14 of the Respective Treatment Period | Day 14, n=23, 24 | 89.4 Beats per minute | Standard Error 1.71 |
| FF 100 µg | Change From Baseline in Heart Rate at Day1 and Day 14 of the Respective Treatment Period | Day 1, n=25, 25 | 88.6 Beats per minute | Standard Error 1.63 |
| FF 100 µg | Change From Baseline in Heart Rate at Day1 and Day 14 of the Respective Treatment Period | Day 14, n=23, 24 | 85.7 Beats per minute | Standard Error 1.67 |
95% CI: [-8.8, 0.4]
95% CI: [-1.1, 8.5]
Primary
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period
SBP and DBP were measured at Day 1 and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1. Change from Baseline was calculated as the Day 14 value minus the Baseline value.
Time frame: Day 1 and Day 14 of the respective treatment period (up to Study Day 63)
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/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 1 SBP, Baseline, n=25, 25 | 97.2 Millimeters of mercury (mmHg) | Standard Deviation 5.41 |
| FF 100 µg/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 1 SBP, 20 minutes, n=25, 25 | -0.1 Millimeters of mercury (mmHg) | Standard Deviation 2.98 |
| FF 100 µg/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 1 SBP, 1 hour, n=25, 25 | 0.5 Millimeters of mercury (mmHg) | Standard Deviation 2.87 |
| FF 100 µg/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 1 SBP, 2 hours, n=25, 25 | 0.9 Millimeters of mercury (mmHg) | Standard Deviation 3.05 |
| FF 100 µg/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 SBP, Pre-dose, n=23, 24 | 1.3 Millimeters of mercury (mmHg) | Standard Deviation 4.32 |
| FF 100 µg/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 SBP, 20 minutes, n=23, 24 | 1.3 Millimeters of mercury (mmHg) | Standard Deviation 4.61 |
| FF 100 µg/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 SBP, 1 hour, n=23, 24 | 1.0 Millimeters of mercury (mmHg) | Standard Deviation 4.42 |
| FF 100 µg/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 SBP, 2 hours, n=23, 24 | 1.7 Millimeters of mercury (mmHg) | Standard Deviation 4.17 |
| FF 100 µg/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 SBP, 4 hours, n=23, 24 | 2.1 Millimeters of mercury (mmHg) | Standard Deviation 4.22 |
| FF 100 µg/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 SBP, 8 hours, n=23, 24 | 2.0 Millimeters of mercury (mmHg) | Standard Deviation 4.33 |
| FF 100 µg/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 1 DBP, Baseline, n=25, 25 | 62.3 Millimeters of mercury (mmHg) | Standard Deviation 3.54 |
| FF 100 µg/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 1 DBP, 20 minutes, n=25, 25 | 0.3 Millimeters of mercury (mmHg) | Standard Deviation 2.81 |
| FF 100 µg/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 1 DBP, 1 hour, n=25, 25 | 1.0 Millimeters of mercury (mmHg) | Standard Deviation 3.17 |
| FF 100 µg/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 1 DBP, 2 hours, n=25, 25 | 0.9 Millimeters of mercury (mmHg) | Standard Deviation 3.42 |
| FF 100 µg/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 DBP, Pre-dose, n=23, 24 | 0.6 Millimeters of mercury (mmHg) | Standard Deviation 3.54 |
| FF 100 µg/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 DBP, 20 minutes, n=23, 24 | 0.1 Millimeters of mercury (mmHg) | Standard Deviation 3.69 |
| FF 100 µg/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 DBP, 1 hour, n=23, 24 | 0.4 Millimeters of mercury (mmHg) | Standard Deviation 4.18 |
| FF 100 µg/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 DBP, 2 hours, n=23, 24 | 1.3 Millimeters of mercury (mmHg) | Standard Deviation 3.75 |
| FF 100 µg/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 DBP, 4 hours, n=23, 24 | 1.1 Millimeters of mercury (mmHg) | Standard Deviation 4.17 |
| FF 100 µg/VI 25 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 DBP, 8 hours, n=23, 24 | 1.4 Millimeters of mercury (mmHg) | Standard Deviation 3.27 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 DBP, 2 hours, n=23, 24 | 0.4 Millimeters of mercury (mmHg) | Standard Deviation 3.19 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 1 SBP, Baseline, n=25, 25 | 99.9 Millimeters of mercury (mmHg) | Standard Deviation 6.71 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 1 DBP, Baseline, n=25, 25 | 63.6 Millimeters of mercury (mmHg) | Standard Deviation 3.86 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 1 SBP, 20 minutes, n=25, 25 | -0.1 Millimeters of mercury (mmHg) | Standard Deviation 4.66 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 DBP, 20 minutes, n=23, 24 | 0.1 Millimeters of mercury (mmHg) | Standard Deviation 2.62 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 1 SBP, 1 hour, n=25, 25 | 0.4 Millimeters of mercury (mmHg) | Standard Deviation 3.7 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 1 DBP, 20 minutes, n=25, 25 | -0.3 Millimeters of mercury (mmHg) | Standard Deviation 3.76 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 1 SBP, 2 hours, n=25, 25 | 1.3 Millimeters of mercury (mmHg) | Standard Deviation 2.95 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 DBP, 8 hours, n=23, 24 | -0.2 Millimeters of mercury (mmHg) | Standard Deviation 3.02 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 SBP, Pre-dose, n=23, 24 | -1.2 Millimeters of mercury (mmHg) | Standard Deviation 6.92 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 1 DBP, 1 hour, n=25, 25 | 0.8 Millimeters of mercury (mmHg) | Standard Deviation 3.11 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 SBP, 20 minutes, n=23, 24 | -1.2 Millimeters of mercury (mmHg) | Standard Deviation 6.03 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 DBP, 1 hour, n=23, 24 | 0.0 Millimeters of mercury (mmHg) | Standard Deviation 2.3 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 SBP, 1 hour, n=23, 24 | -0.8 Millimeters of mercury (mmHg) | Standard Deviation 6.36 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 1 DBP, 2 hours, n=25, 25 | 1.0 Millimeters of mercury (mmHg) | Standard Deviation 3.38 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 SBP, 2 hours, n=23, 24 | -0.8 Millimeters of mercury (mmHg) | Standard Deviation 6.34 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 DBP, 4 hours, n=23, 24 | 1.1 Millimeters of mercury (mmHg) | Standard Deviation 3.35 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 SBP, 4 hours, n=23, 24 | 0.1 Millimeters of mercury (mmHg) | Standard Deviation 6.47 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 DBP, Pre-dose, n=23, 24 | 0.2 Millimeters of mercury (mmHg) | Standard Deviation 3.29 |
| FF 100 µg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Day 1 and Day 14 of the Respective Treatment Period | Day 14 SBP, 8 hours, n=23, 24 | -0.4 Millimeters of mercury (mmHg) | Standard Deviation 7.17 |
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 63)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FF 100 µg/VI 25 µg | Hematocrit Values at Day 14 of the Respective Treatment Period | 0.3816 proportion of 1 | Standard Deviation 0.04199 |
| FF 100 µg | Hematocrit Values at Day 14 of the Respective Treatment Period | 0.3866 proportion of 1 | Standard Deviation 0.0216 |
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 63)
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 |
|---|---|---|---|---|
| FF 100 µg/VI 25 µg | Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Values at Day 14 of the Respective Treatment Period | Hemoglobin, n=21, 23 | 125.9 Grams per liter (g/L) | Standard Deviation 13.49 |
| FF 100 µg/VI 25 µg | Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Values at Day 14 of the Respective Treatment Period | MCHC, n=21, 23 | 330.3 Grams per liter (g/L) | Standard Deviation 5.83 |
| FF 100 µg | Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Values at Day 14 of the Respective Treatment Period | Hemoglobin, n=21, 23 | 128.0 Grams per liter (g/L) | Standard Deviation 6.52 |
| FF 100 µg | Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Values at Day 14 of the Respective Treatment Period | MCHC, n=21, 23 | 330.8 Grams per liter (g/L) | Standard Deviation 7.88 |
Primary
Maximum QTcF at Day 1 and Day 14 of the Respective Treatment Period
QTcF is the QT domain corrected for heart rate by Fridericia's formula. Treatment, period, day (1 and 14), participant Baseline, period Baseline, and treatment\*day interaction were fitted as fixed effects, and participant was fitted as a random effect.
Time frame: Day 1 and Day 14 of the respective treatment period (up to Study Day 63)
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 (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| FF 100 µg/VI 25 µg | Maximum QTcF at Day 1 and Day 14 of the Respective Treatment Period | Day 1 QTcF, n=25, 25 | 403.3 milliseconds | Standard Error 1.98 |
| FF 100 µg/VI 25 µg | Maximum QTcF at Day 1 and Day 14 of the Respective Treatment Period | Day 14 QTcF, n=23, 24 | 404.0 milliseconds | Standard Error 2.06 |
| FF 100 µg | Maximum QTcF at Day 1 and Day 14 of the Respective Treatment Period | Day 1 QTcF, n=25, 25 | 402.2 milliseconds | Standard Error 1.98 |
| FF 100 µg | Maximum QTcF at Day 1 and Day 14 of the Respective Treatment Period | Day 14 QTcF, n=23, 24 | 404.2 milliseconds | Standard Error 2.02 |
95% CI: [-4.4, 6.7]
95% CI: [-6, 5.5]
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 63)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FF 100 µg/VI 25 µg | Mean Corpuscle Hemoglobin (MCH) Values at Day 14 of the Respective Treatment Period | 29.03 10^12 picograms (pg) per cell | Standard Deviation 0.941 |
| FF 100 µg | Mean Corpuscle Hemoglobin (MCH) Values at Day 14 of the Respective Treatment Period | 29.25 10^12 picograms (pg) per cell | Standard Deviation 1.116 |
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 63)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FF 100 µg/VI 25 µg | Mean Corpuscle Volume (MCV) Value at Day 14 of the Respective Treatment Period | 87.9 10^15 femtoliters (fL) per cell | Standard Deviation 2.61 |
| FF 100 µg | Mean Corpuscle Volume (MCV) Value at Day 14 of the Respective Treatment Period | 88.6 10^15 femtoliters (fL) per cell | Standard Deviation 3.37 |
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 9)/Early Withdrawal
Population: All Subjects Population: all participants who received at least one dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FF 100 µg/VI 25 µg | Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period | Any AE | 4 Participants |
| FF 100 µg/VI 25 µg | 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 | 1 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 63)
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 |
|---|---|---|---|---|
| FF 100 µg/VI 25 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 1, Baseline, n=25, 25 | 219.0 liters/minute | Standard Deviation 53.27 |
| FF 100 µg/VI 25 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, Pre-dose, n=23, 24 | 224.8 liters/minute | Standard Deviation 52.86 |
| FF 100 µg/VI 25 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 1, 20 minutes post-dose, n=25, 25 | 222.4 liters/minute | Standard Deviation 53.5 |
| FF 100 µg/VI 25 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, 20 minutes post-dose, n=23, 24 | 227.2 liters/minute | Standard Deviation 52.18 |
| FF 100 µg/VI 25 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 1, 1 hour post-dose, n=25, 25 | 223.2 liters/minute | Standard Deviation 54.23 |
| FF 100 µg/VI 25 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, 2 hours post-dose, n=23, 24 | 235.7 liters/minute | Standard Deviation 53.16 |
| FF 100 µg/VI 25 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 1, 10 minutes post-dose, n=25, 25 | 218.8 liters/minute | Standard Deviation 53.02 |
| FF 100 µg/VI 25 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, 12 hours post-dose, n=23, 24 | 238.9 liters/minute | Standard Deviation 55.84 |
| FF 100 µg/VI 25 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 1, 2 hours post-dose, n=25, 25 | 227.0 liters/minute | Standard Deviation 55.94 |
| 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, 24 | 230.4 liters/minute | Standard Deviation 52.54 |
| FF 100 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 1, Baseline, n=25, 25 | 223.6 liters/minute | Standard Deviation 56.91 |
| FF 100 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 1, 10 minutes post-dose, n=25, 25 | 223.0 liters/minute | Standard Deviation 55.15 |
| 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 | 227.2 liters/minute | Standard Deviation 54.07 |
| 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 | 228.6 liters/minute | Standard Deviation 54.17 |
| FF 100 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, Pre-dose, n=23, 24 | 215.0 liters/minute | Standard Deviation 50.71 |
| FF 100 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 14, 20 minutes post-dose, n=23, 24 | 218.1 liters/minute | Standard Deviation 52.12 |
| 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, 24 | 225.8 liters/minute | Standard Deviation 48.78 |
| FF 100 µg | Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period | Day 1, 20 minutes post-dose, n=25, 25 | 228.2 liters/minute | Standard Deviation 56.73 |
Primary
Reticulocyte and Red Blood Cell (RBC) Values at Day 14 of the Respective Treatment Period
Blood samples were collected for the measurement of reticulocytes and RBCs at Day 14 of the respective treatment period.
Time frame: Day 14 of the respective treatment period (up to Study Day 63)
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 |
|---|---|---|---|---|
| FF 100 µg/VI 25 µg | Reticulocyte and Red Blood Cell (RBC) Values at Day 14 of the Respective Treatment Period | Reticulocytes, n=21, 23 | 0.07220 10^12 cells per liter (TI/L) | Standard Deviation 0.037473 |
| FF 100 µg/VI 25 µg | Reticulocyte and Red Blood Cell (RBC) Values at Day 14 of the Respective Treatment Period | RBCs, n=21, 23 | 4.33 10^12 cells per liter (TI/L) | Standard Deviation 0.467 |
| FF 100 µg | Reticulocyte and Red Blood Cell (RBC) Values at Day 14 of the Respective Treatment Period | Reticulocytes, n=21, 23 | 0.07323 10^12 cells per liter (TI/L) | Standard Deviation 0.032203 |
| FF 100 µg | Reticulocyte and Red Blood Cell (RBC) Values at Day 14 of the Respective Treatment Period | RBCs, n=21, 23 | 4.38 10^12 cells per liter (TI/L) | Standard Deviation 0.199 |
Primary
Total Bilirubin, Direct Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period
Blood samples were collected for the measurement of total bilirubin, direct 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 63)
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 |
|---|---|---|---|---|
| FF 100 µg/VI 25 µg | Total Bilirubin, Direct Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period | Total bilirubin, n=22, 24 | 6.1 Micromoles per liter (µmol/L) | Standard Deviation 1.44 |
| FF 100 µg/VI 25 µg | Total Bilirubin, Direct Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period | Direct bilirubin, n=22, 24 | 1.7 Micromoles per liter (µmol/L) | Standard Deviation 0.7 |
| FF 100 µg/VI 25 µg | Total Bilirubin, Direct Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period | Creatinine, n=22, 24 | 36.00 Micromoles per liter (µmol/L) | Standard Deviation 7.617 |
| FF 100 µg/VI 25 µg | Total Bilirubin, Direct Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period | Uric acid, n=22, 24 | 231.8 Micromoles per liter (µmol/L) | Standard Deviation 64.85 |
| FF 100 µg | Total Bilirubin, Direct Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period | Uric acid, n=22, 24 | 233.8 Micromoles per liter (µmol/L) | Standard Deviation 54.04 |
| FF 100 µg | Total Bilirubin, Direct Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period | Total bilirubin, n=22, 24 | 5.9 Micromoles per liter (µmol/L) | Standard Deviation 1.72 |
| FF 100 µg | Total Bilirubin, Direct Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period | Creatinine, n=22, 24 | 37.09 Micromoles per liter (µmol/L) | Standard Deviation 6.225 |
| FF 100 µg | Total Bilirubin, Direct Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period | Direct bilirubin, n=22, 24 | 1.9 Micromoles per liter (µmol/L) | Standard Deviation 0.41 |
Secondary
AUC(0-t) and AUC(0-4) of FF on Day 14 of the Respective Treatment Period
Area under the concentration-time (AUC) curve from time zero (pre-dose) to the last time AUC(0-t) and from time zero to 4 hours AUC(0-4) of quantifiable concentration of FF on Day 14 of the respective treatment period was measured. Samples were collected at the following times: pre-dose; 10 minutes (min) and 30 min post-dose; and 1, 2, and 4 hours post-dose. 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 PK Population.
Time frame: Day 14 of the respective treatment period (up to Study Day 63)
Population: FF Pharmacokinetic (PK) Population: participants in the All Subjects Population for whom a PK sample was obtained and analyzed for FF.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| FF 100 µg/VI 25 µg | AUC(0-t) and AUC(0-4) of FF on Day 14 of the Respective Treatment Period | AUC(0-t), n=23, 24 | 38.895 picograms*hour per milliliter (pg*hr/mL) |
| FF 100 µg/VI 25 µg | AUC(0-t) and AUC(0-4) of FF on Day 14 of the Respective Treatment Period | AUC(0-4), n=17, 15 | 86.14 picograms*hour per milliliter (pg*hr/mL) |
| FF 100 µg | AUC(0-t) and AUC(0-4) of FF on Day 14 of the Respective Treatment Period | AUC(0-t), n=23, 24 | 32.880 picograms*hour per milliliter (pg*hr/mL) |
| FF 100 µg | AUC(0-t) and AUC(0-4) of FF on Day 14 of the Respective Treatment Period | AUC(0-4), n=17, 15 | 83.83 picograms*hour per milliliter (pg*hr/mL) |
Secondary
AUC(0-t) and AUC(0-4) of VI on Day 14 of the Respective Treatment Period
Area under the concentration-time (AUC) curve from time zero (pre-dose) to the last time AUC(0-t) and from time zero to 4 hours AUC(0-4) of quantifiable concentration of VI on Day 14 of the respective treatment period was measured. Samples were collected at the following times: pre-dose; 10 minutes (min) and 30 min post-dose; and 1, 2, and 4 hours post-dose. 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 VI PK Population.
Time frame: Day 14 of the respective treatment period (up to Study Day 63)
Population: VI PK Population: participants in the All Subjects Population for whom a PK sample was obtained and analyzed for VI.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| FF 100 µg/VI 25 µg | AUC(0-t) and AUC(0-4) of VI on Day 14 of the Respective Treatment Period | AUC(0-t), n=23 | 44.297 picograms*hour per milliliter (pg*hr/mL) |
| FF 100 µg/VI 25 µg | AUC(0-t) and AUC(0-4) of VI on Day 14 of the Respective Treatment Period | AUC(0-4), n=11 | 119.19 picograms*hour per milliliter (pg*hr/mL) |
Secondary
Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on 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.
Time frame: Day 1 and Day 14 of the respective treatment period (up to Study Day 63)
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/VI 25 µg | Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Day 1 and Day 14 of the Respective Treatment Period | Day 1, Average flow rate, n=23, 23 | 41.11 Liters per minute (L/min) | Standard Deviation 11.294 |
| FF 100 µg/VI 25 µg | Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Day 1 and Day 14 of the Respective Treatment Period | Day 14, Average flow rate, n=23, 23 | 42.29 Liters per minute (L/min) | Standard Deviation 10.895 |
| FF 100 µg/VI 25 µg | Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Day 1 and Day 14 of the Respective Treatment Period | Day 1, PIFR, n=23, 23 | 65.85 Liters per minute (L/min) | Standard Deviation 16.649 |
| FF 100 µg/VI 25 µg | Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Day 1 and Day 14 of the Respective Treatment Period | Day 14, PIFR, n=23, 23 | 67.36 Liters per minute (L/min) | Standard Deviation 16.432 |
| FF 100 µg | Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Day 1 and Day 14 of the Respective Treatment Period | Day 14, PIFR, n=23, 23 | 64.79 Liters per minute (L/min) | Standard Deviation 15.886 |
| FF 100 µg | Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Day 1 and Day 14 of the Respective Treatment Period | Day 1, Average flow rate, n=23, 23 | 42.72 Liters per minute (L/min) | Standard Deviation 11.593 |
| FF 100 µg | Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Day 1 and Day 14 of the Respective Treatment Period | Day 1, PIFR, n=23, 23 | 67.60 Liters per minute (L/min) | Standard Deviation 16.097 |
| FF 100 µg | Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Day 1 and Day 14 of the Respective Treatment Period | Day 14, Average flow rate, n=23, 23 | 41.36 Liters per minute (L/min) | Standard Deviation 10.354 |
Secondary
Average Oropharyngeal Cross-sectional Area on Day 1 and Day 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 the 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 (Day 1 and Day 14 of the respective treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated.
Time frame: Day 1 and Day 14 of the respective treatment period (up to Study Day X)
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/VI 25 µg | Average Oropharyngeal Cross-sectional Area on Day 1 and Day 14 of the Respective Treatment Period | Day 1, n=23, 23 | 4.13 centimeters squared (cm^2) | Standard Deviation 2.01 |
| FF 100 µg/VI 25 µg | Average Oropharyngeal Cross-sectional Area on Day 1 and Day 14 of the Respective Treatment Period | Day 14, n=23, 23 | 3.76 centimeters squared (cm^2) | Standard Deviation 2.195 |
| FF 100 µg | Average Oropharyngeal Cross-sectional Area on Day 1 and Day 14 of the Respective Treatment Period | Day 1, n=23, 23 | 3.85 centimeters squared (cm^2) | Standard Deviation 2.043 |
| FF 100 µg | Average Oropharyngeal Cross-sectional Area on Day 1 and Day 14 of the Respective Treatment Period | Day 14, n=23, 23 | 3.70 centimeters squared (cm^2) | Standard Deviation 2.279 |
Secondary
Blood Glucose and Potassium Values on Day 14 of the Respective Treatment Period
Blood glucose and potassium values were measured on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 10 minutes (min) and 30 min post-dose; and 1, 2, and 4 hours post-dose. Weighted means were derived using the linear trapezoidal rule. Actual relative times were used for the calculation except where actual times were missing. If any actual times were missing, planned relative time were used for these observations. Treatment and period were fitted as fixed effects and participant was fitted as a random effect.
Time frame: Day 14 of the respective treatment period (up to Study Day 63)
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 (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| FF 100 µg/VI 25 µg | Blood Glucose and Potassium Values on Day 14 of the Respective Treatment Period | Glucose, n=22, 24 | 5.578 Millimoles per liter (mmol/L) | 95% Confidence Interval 0.1495 |
| FF 100 µg/VI 25 µg | Blood Glucose and Potassium Values on Day 14 of the Respective Treatment Period | Potassium, n=21, 23 | 4.059 Millimoles per liter (mmol/L) | 95% Confidence Interval 0.0448 |
| FF 100 µg | Blood Glucose and Potassium Values on Day 14 of the Respective Treatment Period | Glucose, n=22, 24 | 5.074 Millimoles per liter (mmol/L) | 95% Confidence Interval 0.1443 |
| FF 100 µg | Blood Glucose and Potassium Values on Day 14 of the Respective Treatment Period | Potassium, n=21, 23 | 4.148 Millimoles per liter (mmol/L) | 95% Confidence Interval 0.0426 |
Secondary
Cmax of FF on Day 14 of the Respective Treatment Period
Cmax is defined as the maximum observed concentration of FF on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 10 minutes (min) and 30 min post-dose; and 1, 2, and 4 hours post-dose.
Time frame: Day 14 of the respective treatment period (up to Study Day 63)
Population: FF PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| FF 100 µg/VI 25 µg | Cmax of FF on Day 14 of the Respective Treatment Period | 20.73 picograms per milliliter (pg/mL) |
| FF 100 µg | Cmax of FF on Day 14 of the Respective Treatment Period | 21.16 picograms per milliliter (pg/mL) |
Secondary
Cmax of VI on Day 14 of the Respective Treatment Period
Cmax is defined as the maximum observed concentration of VI on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 10 minutes (min) and 30 min post-dose; and 1, 2, and 4 hours post-dose.
Time frame: Day 14 of the respective treatment period (up to Study Day 63)
Population: Participants received FF 100 µg in one of the two 14-day treatment periods. FF 100 µg 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| FF 100 µg/VI 25 µg | Cmax of VI on Day 14 of the Respective Treatment Period | 44.21 picograms per milliliter (pg/mL) |
Secondary
Distance of Assessment on Day 1 and Day 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 the respective treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated.
Time frame: Day 1 and Day 14 of the respective treatment period (up to Study Day 63)
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/VI 25 µg | Distance of Assessment on Day 1 and Day 14 of the Respective Treatment Period | Day 1, n=23, 23 | 19.20 centimeters (cm) | Standard Deviation 1.097 |
| FF 100 µg/VI 25 µg | Distance of Assessment on Day 1 and Day 14 of the Respective Treatment Period | Day 14, n=23, 23 | 19.26 centimeters (cm) | Standard Deviation 0.717 |
| FF 100 µg | Distance of Assessment on Day 1 and Day 14 of the Respective Treatment Period | Day 1, n=23, 23 | 19.24 centimeters (cm) | Standard Deviation 0.959 |
| FF 100 µg | Distance of Assessment on Day 1 and Day 14 of the Respective Treatment Period | Day 14, n=23, 23 | 19.10 centimeters (cm) | Standard Deviation 1.003 |
Secondary
Ex-throat Dose (ETD) and ETD <2 Microns on 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.
Time frame: Day 14 of the respective treatment period (up to Study Day 63)
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/VI 25 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Nominal ETD FF, n=23, 23 | 24.96 micrograms | Standard Deviation 5.801 |
| FF 100 µg/VI 25 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Minimum ETD FF, n=23, 23 | 23.38 micrograms | Standard Deviation 7.023 |
| FF 100 µg/VI 25 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Maximum ETD FF, n=23, 23 | 26.24 micrograms | Standard Deviation 4.825 |
| FF 100 µg/VI 25 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | ETD <2 microns FF, n=23, 23 | 6.66 micrograms | Standard Deviation 0.948 |
| FF 100 µg/VI 25 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Minimum ETD <2 microns FF, n=23, 23 | 6.45 micrograms | Standard Deviation 0.788 |
| FF 100 µg/VI 25 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Maximum ETD <2 microns FF, n=23, 23 | 6.92 micrograms | Standard Deviation 1.147 |
| FF 100 µg/VI 25 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Nominal ETD VI, n=23, 0 | 8.54 micrograms | Standard Deviation 0.953 |
| FF 100 µg/VI 25 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Minimum ETD VI, n=23, 0 | 8.33 micrograms | Standard Deviation 0.793 |
| FF 100 µg/VI 25 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Maximum ETD VI, n=23, 0 | 8.80 micrograms | Standard Deviation 1.154 |
| FF 100 µg/VI 25 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | ETD <2 microns VI, n=23, 0 | 4.86 micrograms | Standard Deviation 1.162 |
| FF 100 µg/VI 25 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Minimum ETD <2 microns VI, n=23, 0 | 4.60 micrograms | Standard Deviation 0.965 |
| FF 100 µg/VI 25 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Maximum ETD <2 microns VI, n=23, 0 | 5.18 micrograms | Standard Deviation 1.409 |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Minimum ETD <2 microns VI, n=23, 0 | NA micrograms | — |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Nominal ETD FF, n=23, 23 | 24.34 micrograms | Standard Deviation 8.574 |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Nominal ETD VI, n=23, 0 | NA micrograms | — |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Minimum ETD FF, n=23, 23 | 22.99 micrograms | Standard Deviation 9.12 |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | ETD <2 microns VI, n=23, 0 | NA micrograms | — |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Maximum ETD FF, n=23, 23 | 25.48 micrograms | Standard Deviation 8.197 |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Minimum ETD VI, n=23, 0 | NA micrograms | — |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | ETD <2 microns FF, n=23, 23 | 5.97 micrograms | Standard Deviation 1.382 |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Maximum ETD <2 microns VI, n=23, 0 | NA micrograms | — |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Minimum ETD <2 microns FF, n=23, 23 | 5.77 micrograms | Standard Deviation 1.319 |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Maximum ETD VI, n=23, 0 | NA micrograms | — |
| FF 100 µg | Ex-throat Dose (ETD) and ETD <2 Microns on Day 14 of the Respective Treatment Period | Maximum ETD <2 microns FF, n=23, 23 | 6.21 micrograms | Standard Deviation 1.476 |
Secondary
Inhalation Time on Days 1 and 14 of 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 (up to Study Day 63)
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/VI 25 µg | Inhalation Time on Days 1 and 14 of of the Respective Treatment Period | Day 1, n=23, 23 | 0.97 Seconds (sec) | Standard Deviation 0.35 |
| FF 100 µg/VI 25 µg | Inhalation Time on Days 1 and 14 of of the Respective Treatment Period | Day 14, n=23, 23 | 0.96 Seconds (sec) | Standard Deviation 0.314 |
| FF 100 µg | Inhalation Time on Days 1 and 14 of of the Respective Treatment Period | Day 1, n=23, 23 | 0.83 Seconds (sec) | Standard Deviation 0.385 |
| FF 100 µg | Inhalation Time on Days 1 and 14 of of the Respective Treatment Period | Day 14, n=23, 23 | 0.91 Seconds (sec) | Standard Deviation 0.347 |
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 (up to Study Day 63)
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/VI 25 µg | Inhaled Volume on Days 1 and 14 of the Respective Treatment Period | Day 1, n=23, 23 | 0.69 Liters | Standard Deviation 0.337 |
| FF 100 µg/VI 25 µg | Inhaled Volume on Days 1 and 14 of the Respective Treatment Period | Day 14, n=23, 23 | 0.68 Liters | Standard Deviation 0.308 |
| FF 100 µg | Inhaled Volume on Days 1 and 14 of the Respective Treatment Period | Day 1, n=23, 23 | 0.58 Liters | Standard Deviation 0.285 |
| FF 100 µg | Inhaled Volume on Days 1 and 14 of the Respective Treatment Period | Day 14, n=23, 23 | 0.65 Liters | Standard Deviation 0.352 |
Secondary
Oropharyngeal Volume on Day 1 and Day 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: Day 1 and Day 14 of the respective treatment period (up to Study Day 63)
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/VI 25 µg | Oropharyngeal Volume on Day 1 and Day 14 of the Respective Treatment Period | Day 1, n=23, 23 | 79.49 Liters per minute (L/min) | Standard Deviation 43.398 |
| FF 100 µg/VI 25 µg | Oropharyngeal Volume on Day 1 and Day 14 of the Respective Treatment Period | Day 14, n=23, 23 | 72.35 Liters per minute (L/min) | Standard Deviation 42.437 |
| FF 100 µg | Oropharyngeal Volume on Day 1 and Day 14 of the Respective Treatment Period | Day 1, n=23, 23 | 75.54 Liters per minute (L/min) | Standard Deviation 44.195 |
| FF 100 µg | Oropharyngeal Volume on Day 1 and Day 14 of the Respective Treatment Period | Day 14, n=23, 23 | 71.47 Liters per minute (L/min) | Standard Deviation 45.841 |
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 (up to Study Day 63)
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/VI 25 µg | Peak Pressure Drop on Days 1 and 14 of the Respective Treatment Period | Day 1, n=23, 23 | 3.79 Kilopascal (kpa) | Standard Deviation 1.706 |
| FF 100 µg/VI 25 µg | Peak Pressure Drop on Days 1 and 14 of the Respective Treatment Period | Day 14, n=23, 23 | 3.93 Kilopascal (kpa) | Standard Deviation 1.877 |
| FF 100 µg | Peak Pressure Drop on Days 1 and 14 of the Respective Treatment Period | Day 1, n=23, 23 | 3.97 Kilopascal (kpa) | Standard Deviation 1.787 |
| FF 100 µg | Peak Pressure Drop on Days 1 and 14 of the Respective Treatment Period | Day 14, n=23, 23 | 3.67 Kilopascal (kpa) | Standard Deviation 1.611 |
Secondary
Serum Cortisol (SC) Weighted Mean (0-12 Hours) on Day 14 of the Respective Treatment Period
SC weighted mean was determined for each participant over the time period of 0-12 hours on Day 14 of the respective treatment period. SC weighted mean was derived by dividing the area under the concentration-time curve (AUC; defined as thearea under the concentration-time curve from time zero up to 24 hours) by the sample collection time interval. The sample collection time interval is defined as the difference between the time of the last cortisol sample and the time of the first cortisol sample. Samples were collected at the following time points: 0 (first blood draw/pre-dose); 2, 4, 8, and 12 hours (relative to the 0 time point). Weighted means were derived using the linear trapezoidal rule. Actual relative times were used for the calculation except where actual times were missing. If any actual times were missing, planned relative time were used for these observations. Treatment and period were fitted as fixed effects and participant was fitted as a random effect.
Time frame: Day 14 of the respective treatment period (up to Study Day 63)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| FF 100 µg/VI 25 µg | Serum Cortisol (SC) Weighted Mean (0-12 Hours) on Day 14 of the Respective Treatment Period | 193.77 nanomoles per Liter | 95% Confidence Interval 0.069 |
| FF 100 µg | Serum Cortisol (SC) Weighted Mean (0-12 Hours) on Day 14 of the Respective Treatment Period | 192.50 nanomoles per Liter | 95% Confidence Interval 0.069 |
Secondary
Tmax and Tlast of FF on Day 14 of the Respective Treatment Period
tmax is defined as the time to reach the observed maximum concentration, and tlast 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; 10 minutes (min) and 30 min post-dose; and 1, 2, and 4 hours post-dose.
Time frame: Day 14 of the respective treatment period (up to Study Day 63)
Population: FF PK 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 PK Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| FF 100 µg/VI 25 µg | Tmax and Tlast of FF on Day 14 of the Respective Treatment Period | tlast, n=20, 19 | 4.030 hours |
| FF 100 µg/VI 25 µg | Tmax and Tlast of FF on Day 14 of the Respective Treatment Period | tmax, n=20, 19 | 0.965 hours |
| FF 100 µg | Tmax and Tlast of FF on Day 14 of the Respective Treatment Period | tmax, n=20, 19 | 0.500 hours |
| FF 100 µg | Tmax and Tlast of FF on Day 14 of the Respective Treatment Period | tlast, n=20, 19 | 4.020 hours |
Secondary
Tmax and Tlast of VI on Day 1 of the Respective Treatment Period
tmax is defined as the time to reach the observed maximum VI concentration, and tlast is defined as the time of the last observed quantifiable VI concentration on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 10 minutes (min) and 30 min post-dose; and 1, 2, and 4 hours post-dose.
Time frame: Day 14 of the respective treatment period (up to Study Day 63)
Population: VI PK 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 VI PK Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| FF 100 µg/VI 25 µg | Tmax and Tlast of VI on Day 1 of the Respective Treatment Period | tmax, n=21 | 0.170 hours |
| FF 100 µg/VI 25 µg | Tmax and Tlast of VI on Day 1 of the Respective Treatment Period | tlast, n=21 | 3.870 hours |
Secondary
Total Emitted Dose (TED) on 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.
Time frame: Day 14 of the respective treatment period (up to Study Day 63)
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/VI 25 µg | Total Emitted Dose (TED) on Day 14 of the Respective Treatment Period | Nominal TED FF, n=23, 23 | 87.58 micrograms | Standard Deviation 0.305 |
| FF 100 µg/VI 25 µg | Total Emitted Dose (TED) on Day 14 of the Respective Treatment Period | Minimum TED FF, n=23, 23 | 87.64 micrograms | Standard Deviation 0.33 |
| FF 100 µg/VI 25 µg | Total Emitted Dose (TED) on Day 14 of the Respective Treatment Period | Maximum TED FF, n=23, 23 | 87.51 micrograms | Standard Deviation 0.289 |
| FF 100 µg/VI 25 µg | Total Emitted Dose (TED) on Day 14 of the Respective Treatment Period | Nominal TED VI, n=23, 0 | 20.26 micrograms | Standard Deviation 0.162 |
| FF 100 µg/VI 25 µg | Total Emitted Dose (TED) on Day 14 of the Respective Treatment Period | Minimum TED VI, n=23, 0 | 20.22 micrograms | Standard Deviation 0.153 |
| FF 100 µg/VI 25 µg | Total Emitted Dose (TED) on Day 14 of the Respective Treatment Period | Maximum TED VI, n=23, 0 | 20.29 micrograms | Standard Deviation 0.175 |
| FF 100 µg | Total Emitted Dose (TED) on Day 14 of the Respective Treatment Period | Minimum TED VI, n=23, 0 | NA micrograms | — |
| FF 100 µg | Total Emitted Dose (TED) on Day 14 of the Respective Treatment Period | Nominal TED FF, n=23, 23 | 86.33 micrograms | Standard Deviation 1.505 |
| FF 100 µg | Total Emitted Dose (TED) on Day 14 of the Respective Treatment Period | Nominal TED VI, n=23, 0 | NA micrograms | — |
| FF 100 µg | Total Emitted Dose (TED) on Day 14 of the Respective Treatment Period | Minimum TED FF, n=23, 23 | 86.72 micrograms | Standard Deviation 1.589 |
| FF 100 µg | Total Emitted Dose (TED) on Day 14 of the Respective Treatment Period | Maximum TED VI, n=23, 0 | NA micrograms | — |
| FF 100 µg | Total Emitted Dose (TED) on Day 14 of the Respective Treatment Period | Maximum TED FF, n=23, 23 | 85.93 micrograms | Standard Deviation 1.534 |