Pharmacokinetics and PharmacoDynamics of GW685698 in Paedeatric Asthmatic Patients

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT01332292

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

5.4

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will investigate the effect of dosing with flutucasone furoate in asthmatic subjects aged 5-11 years of age. A randomized, two-way crossover, with placebo control, over a 14 day treatment period, it will investigate safety, tolerability, pharmacokinetics and serum cortisol levels.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Fluticasone furoate Drug: Matching placebo	Phase 2

Detailed Description

This study will investigate the effect of dosing with fluticasone furoate 100 μg (micrograms) in asthmatic subjects aged 5-11 years of age. Fluticasone furoate is currently under development as the inhaled corticosteroid component of a combination product containing an inhaled corticosteroid and a long-acting beta-agonist.

The study will be a randomized two-way crossover, with a placebo control. During each treatment period subjects will receive a daily dose via a novel dry powder inhaler for 14 days. Approximately 26 subjects will be recruited to this study, with the aim that 20 will complete the study. Safety, tolerability, pharmacokinetics and serum cortisol levels will be investigated.

Study Design

Study Type:

Interventional

Actual Enrollment :

27 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Placebo-controlled, Two-way Crossover 14-day Study to Investigate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Repeat Dose Inhaled Fluticasone Furoate 100ug (Micrograms) in Children Aged 5-11 Years With Persistent Asthma

Study Start Date :

May 1, 2010

Actual Primary Completion Date :

Jan 1, 2011

Actual Study Completion Date :

Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: COHORT 1 RANDOMISATION A (8-11 years old) Repeat dose session: Fluticasone furoate 100µg; Day 1 and Day 14 = in house dosing; Day 2-13 = home dosing	Drug: Fluticasone furoate Novel dry powder inhaler: 100µg per blister One blister strip containing fluticasone furoate micronised drug blended with lactose and a second blister strip containing lactose and magnesium stearate.
Placebo Comparator: COHORT 1 RANDOMISATION B (8-11 years old) Repeat dose session: matching placebo; Day 1 and Day 14 = in house dosing; Days 2-13 = home dosing	Drug: Matching placebo Novel dry powder inhaler: One blister strip containing lactose and a second blister strip containing lactose and magnesium stearate.
Active Comparator: COHORT 2 RANDOMISATION A (5-7 years old) Repeat dose session: Fluticasone furoate 100µg; Day 1 and Day 14 = in house dosing; Days 2-13 = home dosing	Drug: Fluticasone furoate Novel dry powder inhaler: 100µg per blister One blister strip containing fluticasone furoate micronised drug blended with lactose and a second blister strip containing lactose and magnesium stearate.
Placebo Comparator: COHORT 2 RANDOMISATION B (5-7 years old) Repeat dose session: Matching placebo; Day 1 and Day 14 = in house dosing; Days 2-13 = home dosing	Drug: Matching placebo Novel dry powder inhaler: One blister strip containing lactose and a second blister strip containing lactose and magnesium stearate.

Outcome Measures

Primary Outcome Measures

Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period [From the start of study medication until Week 11 (Visit 6)/Early Withdrawal]
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in deciding whether reporting is appropriate in other situations. Refer to the General Adverse AE/SAE module for a complete list of AEs and SAEs.
Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period [Day 14 of the respective treatment period (up to Study Day 44)]
Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelets, and white blood cell (WBC) count at Day 14 of the respective treatment period.
Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Values at Day 14 of the Respective Treatment Period [Day 14 of the respective treatment period (up to Study Day 44)]
Blood samples were collected for the measurement of hemoglobin and MCHC at Day 14 of the respective treatment period.
Reticulocyte and Red Blood Cell (RBC) Values at Day 14 of the Respective Treatment Period [Day 14 of the respective treatment period (up to Study Day 44)]
Blood samples were collected for the measurement of reticulocyte and RBCs at Day 14 of the respective treatment period.
Hematocrit Values at Day 14 of the Respective Treatment Period [Day 14 of the respective treatment period (up to Study Day 44)]
Blood samples were collected for the measurement of hematocrit at Day 14 of the respective treatment period. Hematocrit is a measure of the percentage of the volume of the whole blood that is composed of red blood cells, as determined by separation of red blood cells from the plasma (usually by centrifugation).
Mean Corpuscle Volume (MCV) Value at Day 14 of the Respective Treatment Period [Day 14 of the respective treatment period (up to Study Day 44)]
Blood samples were collected for the measurement of MCV at Day 14 of the respective treatment period.
Mean Corpuscle Hemoglobin (MCH) Values at Day 14 of the Respective Treatment Period [Day 14 of the respective treatment period (up to Study Day 44)]
Blood samples were collected for the measurement of MCH at Day 14 of the respective treatment period.
Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), and Gamma Glutamyl Transferase (GGT) Values at Day 14 of the Respective Treatment Period [Day 14 of the respective treatment period (up to Study Day 44)]
Blood samples were collected for the measurement of ALT, ALP, AST, and GGT at Day 14 of the respective treatment period.
Albumin and Total Protein Values at Day 14 of the Respective Treatment Period [Day 14 of the respective treatment period (up to Study Day 44)]
Blood samples were collected for the measurement of albumin and total protein at Day 14 of the respective treatment period.
Calcium, Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 14 of the Respective Treatment Period [Day 14 of the respective treatment period (up to Study Day 44)]
Blood samples were collected for the measurement of calcium, chloride, carbon dioxide content/bicarbonate (CO2/BI), glucose, potassium, sodium, and urea/BUN at Day 14 of the respective treatment period.
Total Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period [Day 14 of the respective treatment period (up to Study Day 44)]
Blood samples were collected for the measurement of total bilirubin, creatinine, and uric acid at Day 14 of the respective treatment period.
Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period [Day 1 and Day 14 of the respective treatment period (up to Study Day 44)]
Peak Expiratory Flow (PEF) is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF is calculated as the maximum of three readings taken at each timepoint for each participant. Baseline is defined as the maximum pre-dose measurement at Day 1 for each period.
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period [Baseline and Day 14 of the respective treatment period (up to Study Day 44)]
SBP and DBP were measured at Baseline and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1 for each period.
Heart Rate at Baseline and Day 14 of the Respective Treatment Period [Baseline and Day 14 of the respective treatment period (up to Study Day 44)]
Heart rate (HR) was measured at Baseline and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1 for each period.
Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period [Baseline and Day 14 of the respective treatment period (up to Study Day 44)]
PR, QRS, QT, QTcB, QTcF, and RR were measured at Baseline and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1 for each period. Change from Baseline was calculated as the value at Day 14 minus the Baseline value. QTcB is the QT duration corrected for heart rate by Bazett's formula. QTcF is the QT duration corrected for heart rate by Fridericia's formula.

Secondary Outcome Measures

AUC(0-t) on Day 14 of the Respective Treatment Period [Day 14 of the respective treatment period]
Area under the concentration-time (AUC(0-t)) curve from time zero (pre-dose) to the last time of quantifiable concentration of FF on Day 14 of the respective treatment period was measured. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period. Due to non-quantifiable values, it was not possible to derive AUC(0-12).
Cmax on Day 14 of the Respective Treatment Period [Day 14 of the respective treatment period]
Cmax is defined as the maximum observed concentration on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period.
Tmax and t at Day 14 of the Respective Treatment Period [Day 14 of the respective treatment period]
tmax is defined as the time to reach the observed maximum concentration, and t is defined as the time of the last observed quantifiable concentration on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period.
Serum Cortisol Weighted Mean (0-12 Hours) on Day 14 of the Respective Treatment Period [Day 14 of the respective treatment period]
Serum cortisol weighted mean was determined for each participant over the time period 0-12 hours on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period.
Average Oropharyngeal Cross-sectional Area on Days 1 and 14 of the Respective Treatment Period [Days 1 and 14 of the respective treatment period]
During the pharyngometry assessment, participants inhaled through a wavetube, which had a mouthpiece with the same dimensions as the mouthpiece on the dry powder inhaler used for this study. This technique was used to measure the size of the throat and mouth (oropharynx) in the form of pharyngograms. Pharyngometry data were recorded for each day (Days 1 and 14 of the respective treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated.
Distance of Assessment on Days 1 and 14 of the Respective Treatment Period [Days 1 and 14 of the respective treatment period]
During the pharyngometry assessment, participants inhaled through a wavetube, which had a mouthpiece with the same dimensions as the mouthpiece on the dry powder inhaler used for this study. This technique was used to measure the size of the throat and mouth (oropharynx) in the form of pharyngograms. Distance of assessment is defined as the distance (length measured in centimeters [cm]) estimated to be from the lips to the larynx. Pharyngometry data were recorded for each day (Days 1 and 14 of each treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated.
Oropharyngeal Volume on Days 1 and 14 of the Respective Treatment Period [Days 1 and 14 of the respective treatment period]
During the pharyngometry assessment, participants inhaled through a wavetube, which had a mouthpiece with the same dimensions as the mouthpiece on the dry powder inhaler used for this study. This technique was used to measure the size of the throat and mouth (oropharynx) in the form of pharyngograms. Oropharyngeal volume is defined as the volume (cm^3) of the mouth and throat estimated to be from the lips to the larynx. Pharyngometry data were recorded for each day (Days 1 and 14 of the respective treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated.
Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Days 1 and 14 of the Respective Treatment Period [Day 1 and Day 14 of the respective treatment period]
During the inhalation profile assessment, participants inhaled through a mouthpiece from a device with a similar resistance to the dry powder inhaler used for this study. Average flow rate is defined as the average inspiratory flow rate (Liters [L]/min) across the inhalation profile when inhaling across the resistance of the inhaler. PIFR is defined as the Peak Inspiratory Flow Rate (L/min) of the inhalation profile when inhaling across the resistance of the inhaler.The pressure drop during the inhalation was measured, and the inhalation profiles (pressure drop versus time profile) of the participants were obtained. The mean of the two inhalation profile measurements was used for each day (Days 1 and 14 of the respective treatment period), and the average flow rate and PIFR were determined.
Inhalation Time on Days 1 and 14 of the Respective Treatment Period [Day 1 and Day 14 of the respective treatment period]
During the inhalation profile assessment, participants inhaled through a mouthpiece from a device with a similar resistance to the dry powder inhaler used for this study. Inhalation time is defined as the duration of the inhalation(s) when inhaling across the resistance of the inhaler. The pressure drop during the inhalation was measured, and the inhalation profiles (pressure drop versus time profile) of the participants were obtained. The mean of the two inhalation profile measurements was used for each day (Days 1 and 14 of the respective treatment period), and the inhalation time was determined.
Inhaled Volume on Days 1 and 14 of the Respective Treatment Period [Day 1 and Day 14 of the respective treatment period]
During the inhalation profile assessment, participants inhaled through a mouthpiece from a device with a similar resistance to the dry powder inhaler used for this study. Inhaled volume is defined as the volume of air (Liters) inhaled during the inhalation across the resistance of the inhaler. The pressure drop during the inhalation was measured, and the inhalation profiles (pressure drop versus time profile) of the participants were obtained. The mean of the two inhalation profile measurements was used for each day (Days 1 and 14 of the respective treatment period), and the inhalaled volume was determined.
Peak Pressure Drop on Days 1 and 14 of the Respective Treatment Period [Day 1 and Day 14 of the respective treatment period]
During the inhalation profile assessment, participants inhaled through a mouthpiece from a device with a similar resistance to the dry powder inhaler used for this study. Peak pressure drop is defined as the maximum pressure drop (kilopascal [kPa]) achieved during inhalation across the resistance of the inhaler. The pressure drop during the inhalation was measured, and the inhalation profiles (pressure drop versus time profile) of the participants were obtained. The mean of the two inhalation profile measurements was calculated for each day (Days 1 and 14 of the respective treatment period), and used for subsequent modeling and prediction of dose emission attributes.
Total Emitted Dose (TED) on Days 1 and 14 of the Respective Treatment Period [Day 1 and Day 14 of the respective treatment period]
The total emitted dose (TED) is defined as the mass (micrograms) of the nominal dose that passes beyond the throat. The recorded inhalation profiles of the participants and the mouth-throat (oropharyngeal) models of the sizes that approximated to pharyngometry measurements of the participants were used in conjunction with the electronic Lung (eLung) for in vitro assessment. The eLung is a breathing simulator that replicates the selected inhalation profile with an active inhaler placed at the lips end of the selected ororpharyngeal model. After the dose is emitted from the inhaler, the analysis and assay of throat deposition and material passing beyond the throat was used to derive the nominal, minimum, and maximum predicted total emitted dose.
Ex-throat Dose (ETD) and ETD <2 Microns on Days 1 and 14 of the Respective Treatment Period [Day 1 and Day 14 of the respective treatment period]
The ex-throat dose (ETD) and the "nominal ETD" is the mass (micrograms) of active investigational material that passes beyond the throat, nominal being the mean.The recorded inhalation profiles of the participants and the mouth-throat (oropharyngeal) models of the sizes that approximated to pharyngometry measurements of the participants were used in conjunction with the electronic Lung (eLung) for in vitro assessment. The eLung is a breathing simulator that replicates the selected inhalation profile with an active inhaler placed at the lips end of the selected ororpharyngeal model. After the dose is emitted from the inhaler, the analysis and assay of throat deposition and material passing beyond the throat was used to derive the nominal, minimum, and maximum predicted ETD and ETD <2 microns.

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 11 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male and pre-menarchial female subjects aged 5-11 years on the last planned treatment day are eligible for this study. Pre-menarchial females are defined as any female who has yet to begin menses and is considered Tanner Stage 2 or less.
Diagnosis of asthma at least 6 months prior to screening.
Patients must be controlled on their existing asthma treatment at screening as defined by a Childhood Asthma Control Test score of >19 and PEF (Peak Expiratory Flow) ≥80% predicted.
Apart from asthma, eczema and rhinitis, subjects should be healthy and suffer from no other significant medical conditions.
Subjects must be taking a stable regimen of a short acting beta-agonist inhaler on an as-need basis for at least 4 weeks prior to screening.
Subjects must weigh at least 15 kg (kilograms).
Subjects must demonstrate ability to accept and effectively use the fluticasone furoate devices using the demonstration kits provided to the site.
Subjects and parents/guardians must be able to understand and comply with protocol requirements, instructions and protocol-stated restrictions. Parents/guardians must have the ability to read, write and record diary information collected throughout the study. They must also have the ability to manage study drug administration and PEF assessments.
A signed and dated written informed consent from at least one parent/guardian, and accompanying informed assent from the subject prior to admission to the study.

Exclusion Criteria:

Subjects who have changed their asthma medication within 4 weeks of screening or subjects currently being treated with inhaled corticosteroids or have received such treatment within 4 weeks of screening. In addition, subjects currently receiving (or have received within 4 weeks of screening) any of the following asthma therapies: theophyllines, long-acting inhaled beta-agonists or oral beta-agonists.
Any medical condition or circumstance making the volunteer unsuitable for participation in the study (e.g. history of life-threatening asthma).
Any clinically relevant abnormality identified on the screening medical assessment, including asthma exacerbation requiring systemic corticosteroids (oral, intramuscular, intravenous) or emergency room attendance within 3 months or asthma exacerbation requiring hospitalization within 6 months prior to screening.
Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks of screening and led to a change in asthma management or, in the opinion of the Investigator, is expected to affect the subject's asthma status or the subject's ability to participate in the study.
Clinical visual evidence of oral candidiasis at screening.
Parent/guardian has history of psychiatric disease, intellectual deficiency, substance abuse, or other condition (e.g., inability to read, comprehend and write) which will limit the validity of consent to participate in this study.
Any adverse reaction including immediate or delayed hypersensitivity to any beta-2-agonist, sympathomimetic drug, or any intranasal, inhaled or systemic corticosteroid therapy.
Known or suspected sensitivity to the constituents of the novel dry powder inhaler (i.e., lactose or magnesium stearate), for example, history of severe milk protein allergy.
A subject will not be eligible for this study if he/she is an immediate family member of the participating Investigator, sub-Investigator, study coordinator, or employee of the participating Investigator.
Children who are wards of the state or government.
Evidence of clinically significant abnormality in the 12-lead ECG (electrocardiogram) at screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Cypress	California	United States	90630
2	GSK Investigational Site	Huntington Beach	California	United States	92647
3	GSK Investigational Site	Denver	Colorado	United States	80206
4	GSK Investigational Site	Normal	Illinois	United States	61761
5	GSK Investigational Site	Medford	Oregon	United States	97504

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

None provided.

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT01332292

Other Study ID Numbers:

102942

First Posted:

Apr 11, 2011

Last Update Posted:

Mar 23, 2017

Last Verified:

Feb 1, 2017

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Keywords provided by GlaxoSmithKline

Additional relevant MeSH terms:

Asthma

Fluticasone

Xhance

Study Results

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 Detail	A Baseline assessment was carried out on Day 1 of the first treatment period. Participants were then randomized to one of the two possible treatment sequences (fluticasone furoate [FF] 100 µg followed by placebo; placebo followed by FF 100 µg). Results are reported by intervention, regardless of the age of the participant.

Arm/Group Title	Sequence 1: FF 100 µg Followed by Placebo	Sequence 2: Placebo Followed by FF 100 µg
Arm/Group Description	Participants received fluticasone furoate (FF) 100 micrograms (µg) in Treatment Period 1 and matching placebo in Treatment Period 2. Inhaled FF 100 µg and matching placebo were administered once daily in the morning (Day 1 to Day 14) via a Dry Powder Inhaler. The washout period between the 14-day treatment periods was at least 7 days.	Participants received placebo in Treatment Period 1 and FF 100 µg in Treatment Period 2. Inhaled FF 100 µg and matching placebo were administered once daily in the morning (Day 1 to Day 14) via a Dry Powder Inhaler. The washout period between the 14-day treatment periods was at least 7 days.
Period Title: Treatment Period 1 (14 Days)
STARTED	14	13
COMPLETED	12	12
NOT COMPLETED	2	1
Period Title: Treatment Period 1 (14 Days)
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0
Period Title: Treatment Period 1 (14 Days)
STARTED	12	12
COMPLETED	11	11
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	FF 100 µg/Placebo or Placebo/FF 100 µg
Arm/Group Description	Participants received either fluticasone furoate (FF) 100 micrograms (µg) or matching placebo in the first of two 14-day treatment periods, followed by the other therapy (the therapy not received in the first treatment period) in the second 14-day treatment period. Inhaled FF 100 µg or matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.
Overall Participants	27
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	8.2 (2.08)
Sex: Female, Male (Count of Participants)
Female	13 48.1%
Male	14 51.9%
Race/Ethnicity, Customized (participants) [Number]
African American/African Heritage	9 33.3%
White	16 59.3%
African American/African Heritage & White	1 3.7%
Unknown; Child Was Adopted	1 3.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period
Description	An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in deciding whether reporting is appropriate in other situations. Refer to the General Adverse AE/SAE module for a complete list of AEs and SAEs.
Time Frame	From the start of study medication until Week 11 (Visit 6)/Early Withdrawal

Outcome Measure Data

Analysis Population Description
All Subjects Population: all participants who received at least one dose of study medication

Arm/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	25	26
Any AE	4 14.8%	8 NaN
Any SAE	0 0%	0 NaN

2. Primary Outcome

Title	Basophil, Eosinophil, Lymphocyte, Monocyte, Total Neutrophil, Platelet, and White Blood Cell Count Values at Day 14 of the Respective Treatment Period
Description	Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelets, and white blood cell (WBC) count at Day 14 of the respective treatment period.
Time Frame	Day 14 of the respective treatment period (up to Study Day 44)

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	25	26
Basophils, n=23, 21	0.022 (0.0153)	0.022 (0.0154)
Eosinophils, n=23, 21	0.308 (0.2204)	0.252 (0.2182)
Lymphocytes, n=23, 21	2.595 (0.7834)	2.430 (0.6563)
Monocytes, n=23, 21	0.280 (0.1669)	0.270 (0.1204)
Total neutrophils, n=23, 21	2.740 (1.2091)	3.209 (1.3103)
Platelets, n=23, 20	266.4 (48.59)	263.3 (55.90)
WBCs, n=23, 21	5.94 (1.696)	6.18 (1.513)

3. Primary Outcome

Title	Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Values at Day 14 of the Respective Treatment Period
Description	Blood samples were collected for the measurement of hemoglobin and MCHC at Day 14 of the respective treatment period.
Time Frame	Day 14 of the respective treatment period (up to Study Day 44)

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Novel Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled FF 100 µg was administered once daily in the morning (Day 1 to Day 14) via the Novel Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.
Measure Participants	25	26
Hemoglobin, n=23, 21	129.1 (7.15)	129.6 (6.50)
MCHC, n=23, 21	336.4 (7.66)	336.6 (7.80)

4. Primary Outcome

Title	Reticulocyte and Red Blood Cell (RBC) Values at Day 14 of the Respective Treatment Period
Description	Blood samples were collected for the measurement of reticulocyte and RBCs at Day 14 of the respective treatment period.
Time Frame	Day 14 of the respective treatment period (up to Study Day 44)

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	25	26
Reticulocytes, n=23, 21	0.04952 (0.024497)	0.04499 (0.021309)
RBCs, n=23, 21	4.43 (0.277)	4.46 (0.296)

5. Primary Outcome

Title	Hematocrit Values at Day 14 of the Respective Treatment Period
Description	Blood samples were collected for the measurement of hematocrit at Day 14 of the respective treatment period. Hematocrit is a measure of the percentage of the volume of the whole blood that is composed of red blood cells, as determined by separation of red blood cells from the plasma (usually by centrifugation).
Time Frame	Day 14 of the respective treatment period (up to Study Day 44)

Outcome Measure Data

Analysis Population Description
All Subjects Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	23	21
Mean (Standard Deviation) [percentage of red blood cells in blood]	0.3840 (0.02621)	0.3854 (0.02296)

6. Primary Outcome

Title	Mean Corpuscle Volume (MCV) Value at Day 14 of the Respective Treatment Period
Description	Blood samples were collected for the measurement of MCV at Day 14 of the respective treatment period.
Time Frame	Day 14 of the respective treatment period (up to Study Day 44)

Outcome Measure Data

Analysis Population Description
All Subjects Population. Only those participants available at the specified time points were analyzed .

Arm/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	23	21
Mean (Standard Deviation) [10^15 femtoliters (fL) per cell]	86.8 (4.05)	86.9 (4.40)

7. Primary Outcome

Title	Mean Corpuscle Hemoglobin (MCH) Values at Day 14 of the Respective Treatment Period
Description	Blood samples were collected for the measurement of MCH at Day 14 of the respective treatment period.
Time Frame	Day 14 of the respective treatment period (up to Study Day 44)

Outcome Measure Data

Analysis Population Description
All Subjects Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	23	21
Mean (Standard Deviation) [10^12 picograms (pg) per cell]	29.18 (1.279)	29.24 (1.458)

8. Primary Outcome

Title	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
Description	Blood samples were collected for the measurement of ALT, ALP, AST, and GGT at Day 14 of the respective treatment period.
Time Frame	Day 14 of the respective treatment period (up to Study Day 44)

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	25	26
ALT, n=22, 20	12.2 (3.06)	13.0 (6.04)
ALP, n=22, 20	257.8 (59.24)	260.7 (64.15)
AST, n=22, 19	26.8 (4.39)	26.1 (4.53)
GGT, n=22, 20	14.3 (3.58)	15.4 (4.50)

9. Primary Outcome

Title	Albumin and Total Protein Values at Day 14 of the Respective Treatment Period
Description	Blood samples were collected for the measurement of albumin and total protein at Day 14 of the respective treatment period.
Time Frame	Day 14 of the respective treatment period (up to Study Day 44)

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	25	26
Albumin, n=22, 20	43.0 (2.26)	42.9 (1.83)
Total protein, n=22, 20	67.8 (2.98)	67.8 (2.57)

10. Primary Outcome

Title	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
Description	Blood samples were collected for the measurement of calcium, chloride, carbon dioxide content/bicarbonate (CO2/BI), glucose, potassium, sodium, and urea/BUN at Day 14 of the respective treatment period.
Time Frame	Day 14 of the respective treatment period (up to Study Day 44)

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	25	26
Calcium, n=20, 19	2.371 (0.0791)	2.366 (0.0626)
Chloride, n=22, 20	105.2 (1.93)	104.7 (1.72)
CO2 content/bicarbonate, n=20, 19	17.4 (2.04)	17.8 (1.86)
Glucose, n=22, 20	5.13 (0.614)	4.86 (0.319)
Potassium, n=20, 19	4.24 (0.2564)	4.24 (0.289)
Sodium, n=22, 20	138.3 (1.55)	137.4 (1.54)
Urea/BUN, n=22, 20	4.66 (0.993)	4.83 (1.331)

11. Primary Outcome

Title	Total Bilirubin, Creatinine, and Uric Acid Values at Day 14 of the Respective Treatment Period
Description	Blood samples were collected for the measurement of total bilirubin, creatinine, and uric acid at Day 14 of the respective treatment period.
Time Frame	Day 14 of the respective treatment period (up to Study Day 44)

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	25	26
Total bilirubin, n= 22, 20	5.9 (2.27)	5.6 (1.23)
Creatinine, n= 22, 20	39.89 (7.775)	40.62 (8.421)
Uric acid, n= 22, 20	237.7 (65.46)	234.5 (70.97)

12. Primary Outcome

Title	Peak Expiratory Flow on Day 1 and Day 14 of the Respective Treatment Period
Description	Peak Expiratory Flow (PEF) is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF is calculated as the maximum of three readings taken at each timepoint for each participant. Baseline is defined as the maximum pre-dose measurement at Day 1 for each period.
Time Frame	Day 1 and Day 14 of the respective treatment period (up to Study Day 44)

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	25	25
Day 1, Baseline, n=25, 25	242.3 (77.68)	238.4 (64.98)
Day 1, 15 minutes post-dose, n=25, 25	242.1 (78.98)	238.2 (58.97)
Day 1, 30 minutes post-dose, n=25, 25	249.2 (78.07)	246.0 (62.65)
Day 1, 1 hour post-dose, n=25, 25	247.7 (72.54)	247.0 (64.75)
Day 1, 2 hours post-dose, n=25, 25	252.3 (89.08)	252.6 (61.77)
Day 14, Pre-dose, n=24, 23	242.0 (73.60)	240.6 (83.88)
Day 14, 30 minutes post-dose, n=23, 23	246.1 (81.17)	238.8 (88.78)
Day 14, 1 hours post-dose, n=23, 23	247.0 (77.95)	237.6 (78.66)
Day 14, 2 hours post-dose, n=23, 23	249.5 (74.09)	242.3 (72.02)
Day 14, 4 hours post-dose, n=23, 23	250.6 (82.43)	246.2 (70.43)
Day 14, 7 hours post-dose, n=23, 23	246.3 (79.07)	232.1 (59.82)
Day 14, 12 hours post-dose, n=23, 23	241.9 (75.80)	245.6 (76.68)

13. Primary Outcome

Title	Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline and Day 14 of the Respective Treatment Period
Description	SBP and DBP were measured at Baseline and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1 for each period.
Time Frame	Baseline and Day 14 of the respective treatment period (up to Study Day 44)

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	25	26
Day 1 SBP, Predose, n=25, 26	103.1 (9.29)	102.9 (9.68)
Day 1 SBP, 30 minutes, n=25, 26	101.2 (8.57)	103.8 (10.44)
Day 1 SBP, 1 hour, n=25, 26	102.7 (11.11)	105.2 (11.19)
Day 1 SBP, 2 hours, n=25, 26	102.9 (9.98)	103.9 (9.04)
Day 14 SBP, Predose, n=24, 23	101.8 (8.04)	102.1 (9.92)
Day 14 SBP, 1 hour, n=23, 23	102.6 (9.14)	103.1 (8.04)
Day 14 SBP, 4 hours, n=23, 23	102.0 (9.07)	102.7 (9.43)
Day 14 SBP, 7 hours, n=23, 23	103.4 (9.34)	103.9 (9.88)
Day 14 SBP, 12 hours, n=23, 23	103.2 (7.42)	106.3 (10.61)
Day 1 DBP, Predose, n=25, 26	62.0 (9.71)	61.7 (7.66)
Day 1 DBP, 30 minutes, n=25, 26	63.0 (9.09)	62.6 (6.39)
Day 1 DBP, 1 hour, n=25, 26	61.4 (8.69)	62.3 (8.73)
Day 1 DBP, 2 hours, n=25, 26	63.0 (8.34)	61.2 (8.39)
Day 14 DBP, Predose, n=24, 23	61.3 (6.91)	61.4 (6.81)
Day 14 DBP, 1 hour, n=23, 23	63.9 (10.14)	62.7 (6.88)
Day 14 DBP, 4 hours, n=23, 23	60.4 (8.81)	60.5 (6.73)
Day 14 DBP, 7 hours, n=23, 23	61.8 (9.27)	62.3 (8.23)
Day 14 DBP, 12 hours, n=23, 23	62.0 (8.10)	63.9 (8.68)

14. Primary Outcome

Title	Heart Rate at Baseline and Day 14 of the Respective Treatment Period
Description	Heart rate (HR) was measured at Baseline and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1 for each period.
Time Frame	Baseline and Day 14 of the respective treatment period (up to Study Day 44)

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	25	26
Day 1, Baseline, n=25, 26	78.7 (13.18)	75.9 (11.48)
Day 1, 30 minutes, n=25, 26	78.5 (13.99)	75.5 (10.90)
Day 1, 1 hour, n=25, 26	78.6 (12.62)	77.6 (11.49)
Day 1, 2 hours, n=25, 26	80.6 (13.30)	79.6 (11.78)
Day 14, Predose, n=24, 23	76.8 (13.52)	74.5 (10.60)
Day 14, 1 hour, n=23, 23	80.3 (14.76)	76.2 (8.60)
Day 14, 4 hours, n=23, 23	78.2 (10.46)	77.7 (9.77)
Day 14, 7 hours, n=23, 23	83.1 (14.65)	81.2 (12.13)
Day 14, 12 hours, n=23, 23	83.6 (11.70)	81.1 (10.71)

15. Secondary Outcome

Title	AUC(0-t) on Day 14 of the Respective Treatment Period
Description	Area under the concentration-time (AUC(0-t)) curve from time zero (pre-dose) to the last time of quantifiable concentration of FF on Day 14 of the respective treatment period was measured. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period. Due to non-quantifiable values, it was not possible to derive AUC(0-12).
Time Frame	Day 14 of the respective treatment period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic (PK) Population: all participants in the All Subjects Population for whom a PK sample was obtained and analyzed

Arm/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	0	23
Geometric Mean (95% Confidence Interval) [picogramshour per milliliter (pghr/mL)]	91.29

16. Secondary Outcome

Title	Cmax on Day 14 of the Respective Treatment Period
Description	Cmax is defined as the maximum observed concentration on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period.
Time Frame	Day 14 of the respective treatment period

Outcome Measure Data

Analysis Population Description
PK Population

Arm/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	0	23
Geometric Mean (95% Confidence Interval) [picograms per milliliter (pg/mL)]	24.68

17. Secondary Outcome

Title	Tmax and t at Day 14 of the Respective Treatment Period
Description	tmax is defined as the time to reach the observed maximum concentration, and t is defined as the time of the last observed quantifiable concentration on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period.
Time Frame	Day 14 of the respective treatment period

Outcome Measure Data

Analysis Population Description
PK Population. Only those participant who had quantifiable FF concentrations were analyzed.

Arm/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	0	22
tmax	0.863 (0.7926)
t	6.953 (4.0875)

18. Secondary Outcome

Title	Serum Cortisol Weighted Mean (0-12 Hours) on Day 14 of the Respective Treatment Period
Description	Serum cortisol weighted mean was determined for each participant over the time period 0-12 hours on Day 14 of the respective treatment period. Samples were collected at the following times: pre-dose; 30 minutes, 1, 2, 4, 7, and 12 hours post-dose on Day 14 of the respective treatment period.
Time Frame	Day 14 of the respective treatment period

Outcome Measure Data

Analysis Population Description
All Subjects Population. Only those participants available at the specified time point were analyzed.

Arm/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	22	23
Geometric Mean (95% Confidence Interval) [nanomoles per Liter]	178.76	150.41

19. Secondary Outcome

Title	Average Oropharyngeal Cross-sectional Area on Days 1 and 14 of the Respective Treatment Period
Description	During the pharyngometry assessment, participants inhaled through a wavetube, which had a mouthpiece with the same dimensions as the mouthpiece on the dry powder inhaler used for this study. This technique was used to measure the size of the throat and mouth (oropharynx) in the form of pharyngograms. Pharyngometry data were recorded for each day (Days 1 and 14 of the respective treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated.
Time Frame	Days 1 and 14 of the respective treatment period

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	25	26
Day 1, n=14, 18	4.06 (1.875)	4.24 (1.677)
Day 14, n= 12, 12	5.49 (1.586)	4.58 (1.497)

20. Secondary Outcome

Title	Distance of Assessment on Days 1 and 14 of the Respective Treatment Period
Description	During the pharyngometry assessment, participants inhaled through a wavetube, which had a mouthpiece with the same dimensions as the mouthpiece on the dry powder inhaler used for this study. This technique was used to measure the size of the throat and mouth (oropharynx) in the form of pharyngograms. Distance of assessment is defined as the distance (length measured in centimeters [cm]) estimated to be from the lips to the larynx. Pharyngometry data were recorded for each day (Days 1 and 14 of each treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated.
Time Frame	Days 1 and 14 of the respective treatment period

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	25	26
Day 1, n=14, 18	18.63 (1.736)	18.69 (1.432)
Day 14, n= 12, 12	19.37 (1.823)	18.61 (1.942)

21. Secondary Outcome

Title	Oropharyngeal Volume on Days 1 and 14 of the Respective Treatment Period
Description	During the pharyngometry assessment, participants inhaled through a wavetube, which had a mouthpiece with the same dimensions as the mouthpiece on the dry powder inhaler used for this study. This technique was used to measure the size of the throat and mouth (oropharynx) in the form of pharyngograms. Oropharyngeal volume is defined as the volume (cm^3) of the mouth and throat estimated to be from the lips to the larynx. Pharyngometry data were recorded for each day (Days 1 and 14 of the respective treatment period) using the mean of four measurements (pharyngograms), and the average oropharyngeal cross-sectional area was calculated.
Time Frame	Days 1 and 14 of the respective treatment period

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	25	26
Day 1, n=14, 18	74.19 (32.402)	78.86 (31.092)
Day 14, n= 12, 12	106.31 (33.188)	86.22 (34.363)

22. Secondary Outcome

Title	Average Flow Rate and Peak Inspiratory Flow Rate (PIFR) on Days 1 and 14 of the Respective Treatment Period
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	25	26
Day 1 Average flow rate, n=21, 20	35.38 (11.441)	34.65 (10.840)
Day 14 Average flow rate, n=21, 22	36.25 (11.243)	36.17 (12.772)
Day 1 PIFR, n=21, 20	51.83 (17.286)	52.90 (16.028)
Day 14 PIFR, n=21, 22	55.70 (16.589)	54.76 (17.986)

23. Secondary Outcome

Title	Inhalation Time on Days 1 and 14 of the Respective Treatment Period
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	25	26
Day 1, n=21, 20	1.71 (0.534)	1.93 (0.861)
Day 14, n= 21, 22	1.60 (0.802)	1.61 (0.858)

24. Secondary Outcome

Title	Inhaled Volume on Days 1 and 14 of the Respective Treatment Period
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	25	26
Day 1, n=21, 20	0.99 (0.461)	1.07 (0.480)
Day 14, n= 21, 22	1.00 (0.580)	0.95 (0.541)

25. Secondary Outcome

Title	Peak Pressure Drop on Days 1 and 14 of the Respective Treatment Period
Description	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

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	25	26
Day 1, n=21, 20	2.44 (1.630)	2.53 (1.560)
Day 14, n= 21, 22	2.78 (1.543)	2.74 (1.609)

26. Secondary Outcome

Title	Total Emitted Dose (TED) on Days 1 and 14 of the Respective Treatment Period
Description	The total emitted dose (TED) is defined as the mass (micrograms) of the nominal dose that passes beyond the throat. The recorded inhalation profiles of the participants and the mouth-throat (oropharyngeal) models of the sizes that approximated to pharyngometry measurements of the participants were used in conjunction with the electronic Lung (eLung) for in vitro assessment. The eLung is a breathing simulator that replicates the selected inhalation profile with an active inhaler placed at the lips end of the selected ororpharyngeal model. After the dose is emitted from the inhaler, the analysis and assay of throat deposition and material passing beyond the throat was used to derive the nominal, minimum, and maximum predicted total emitted dose.
Time Frame	Day 1 and Day 14 of the respective treatment period

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	0	26
Day 1, Nominal TED, n=0, 20	85.35 (1.576)
Day 14, Nominal TED, n=0, 22	85.57 (1.857)
Day 1, Minimum TED, n=0, 20	84.84 (1.617)
Day 14, Minimum TED, n=0, 22	85.17 (1.905)
Day 1, Maximum TED, n=0, 20	85.86 (1.639)
Day 14, Maximum TED, n=0, 22	85.97 (1.861)

27. Secondary Outcome

Title	Ex-throat Dose (ETD) and ETD <2 Microns on Days 1 and 14 of the Respective Treatment Period
Description	The ex-throat dose (ETD) and the "nominal ETD" is the mass (micrograms) of active investigational material that passes beyond the throat, nominal being the mean.The recorded inhalation profiles of the participants and the mouth-throat (oropharyngeal) models of the sizes that approximated to pharyngometry measurements of the participants were used in conjunction with the electronic Lung (eLung) for in vitro assessment. The eLung is a breathing simulator that replicates the selected inhalation profile with an active inhaler placed at the lips end of the selected ororpharyngeal model. After the dose is emitted from the inhaler, the analysis and assay of throat deposition and material passing beyond the throat was used to derive the nominal, minimum, and maximum predicted ETD and ETD <2 microns.
Time Frame	Day 1 and Day 14 of the respective treatment period

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	0	26
Day 1, Nominal ETD, n=0, 17	29.37 (2.874)
Day 14, Nominal ETD, n=0, 12	29.83 (2.528)
Day 1, Minimum ETD, n=0, 17	28.47 (3.241)
Day 14, Minimum ETD, n=0, 12	29.35 (2.664)
Day 1, Maximum ETD, n=0, 17	30.26 (2.598)
Day 14, Maximum ETD, n=0, 12	30.26 (2.472)
Day 1, ETD <2 microns, n=0, 17	5.13 (0.498)
Day 14, ETD <2 microns, n=0, 12	5.07 (0.455)
Day 1, Minimum ETD <2 microns, n=0, 17	4.96 (0.459)
Day 14, Minimum ETD <2 microns, n=0, 12	4.99 (0.448)
Day 1, Maximum ETD <2 microns, n=0, 17	5.30 (0.559)
Day 14, Maximum ETD <2 microns, n=0, 12	5.17 (0.476)

28. Primary Outcome

Title	Change From Baseline in the Indicated Electrocardiographic (ECG) Parameters at the Indicated Time Points on Day 14 of the Respective Treatment Period
Description	PR, QRS, QT, QTcB, QTcF, and RR were measured at Baseline and Day 14 of the respective treatment period. Baseline is defined as the pre-dose measurement at Day 1 for each period. Change from Baseline was calculated as the value at Day 14 minus the Baseline value. QTcB is the QT duration corrected for heart rate by Bazett's formula. QTcF is the QT duration corrected for heart rate by Fridericia's formula.
Time Frame	Baseline and Day 14 of the respective treatment period (up to Study Day 44)

Outcome Measure Data

Analysis Population Description
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/Group Title	Placebo	FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.	All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
Measure Participants	25	26
Day 1 PR Interval, 30 minutes, n=25, 26	6.4 (6.37)	7.5 (7.54)
Day 1 PR Interval, 1 hour, n=25, 26	7.3 (6.68)	8.4 (7.17)
Day 1 PR Interval, 2 hours, n=25, 26	8.0 (8.61)	9.5 (10.48)
Day 14 PR Interval, Predose, n=24, 23	7.8 (6.76)	9.6 (9.82)
Day 14 PR Interval, 1 hour, n=23, 23	8.7 (6.74)	8.3 (6.03)
Day 14 PR Interval, 4 hours, n=23, 23	6.4 (3.70)	8.9 (6.86)
Day 14 PR Interval, 7 hour, n=23, 23	8.3 (6.56)	10.2 (10.09)
Day 14 PR Interval, 12 hours, n=22, 23	7.2 (7.50)	9.7 (6.54)
Day 1 QRS Interval, 30 minutes, n=25, 26	4.6 (3.46)	5.2 (4.70)
Day 1 QRS Interval, 1 hour, n=25, 26	4.1 (2.84)	4.4 (3.86)
Day 1 QRS Interval, 2 hours, n=25, 26	4.0 (2.64)	4.5 (3.61)
Day 14 QRS Interval, Predose, n=24, 23	4.2 (3.71)	4.7 (4.29)
Day 14 QRS Interval, 1 hour, n=23, 23	5.7 (3.54)	5.3 (4.71)
Day 14 QRS Interval, 4 hours, n=23, 23	5.6 (3.85)	4.9 (3.93)
Day 14 QRS Interval, 7 hours, n=23, 23	6.1 (5.25)	4.3 (4.22)
Day 14 QRS Interval, 12 hours, n=23, 23	5.0 (4.70)	4.8 (4.02)
Day 1 QT Interval, 30 minutes, n=25, 26	9.8 (8.14)	10.5 (9.57)
Day 1 QT Interval, 1 hour, n=25, 26	13.1 (11.04)	12.7 (11.53)
Day 1 QT Interval, 2 hours, n=25, 26	17.5 (13.88)	15.5 (13.83)
Day 14 QT Interval, Predose, n=24, 23	12.5 (9.81)	15.5 (13.34)
Day 14 QT Interval, 1 hour, n=23, 23	11.4 (6.45)	15.9 (11.11)
Day 14 QT Interval, 4 hours, n=23, 23	13.3 (9.65)	16.7 (12.52)
Day 14 QT Interval, 7 hours, n=23, 23	14.7 (10.94)	15.3 (11.93)
Day 14 QT Interval, 12 hours, n=23, 23	14.7 (10.42)	24.8 (14.93)
Day 1 QTcB Interval, 30 minutes, n=25, 26	15.4 (14.44)	14.2 (11.64)
Day 1 QTcB Interval, 1 hour, n=25, 26	17.3 (13.46)	17.7 (13.18)
Day 1 QTcB Interval, 2 hours, n=25, 26	13.6 (11.07)	18.2 (17.54)
Day 14 QTcB Interval, Predose, n=24, 23	20.7 (15.54)	17.9 (14.92)
Day 14 QTcB Interval, 1 hour, n=23, 23	16.6 (9.43)	16.2 (9.71)
Day 14 QTcB Interval, 4 hours, n=23, 23	14.7 (9.13)	16.8 (9.23)
Day 14 QTcB Interval, 7 hours, n=23, 23	14.5 (10.14)	19.6 (12.03)
Day 14 QTcB Interval, 12 hours, n=23, 23	13.8 (10.70)	18.5 (15.70)
Day 1 QTcF Interval, 30 minutes, n=25, 26	10.8 (9.31)	11.8 (9.30)
Day 1 QTcF Interval, 1 hour, n=25, 26	11.6 (9.57)	12.6 (10.00)
Day 1 QTcF Interval, 2 hours, n=25, 26	10.4 (8.36)	15.4 (12.88)
Day 14 QTcF Interval, Predose, n=24, 23	14.2 (9.92)	12.6 (10.99)
Day 14 QTcF Interval, 1 hour, n=23, 23	9.3 (6.09)	11.4 (9.56)
Day 14 QTcF Interval, 4 hours, n=23, 23	7.8 (6.97)	15.7 (7.41)
Day 14 QTcF Interval, 7 hours, n=23, 23	9.3 (7.77)	15.0 (9.51)
Day 14 QTcF Interval, 12 hours, n=23, 23	8.8 (5.84)	15.8 (11.61)
Day 1 RR Interval, 30 minutes, n=25, 26	70.4 (66.47)	54.2 (44.61)
Day 1 RR Interval, 1 hour, n=25, 26	93.5 (64.97)	90.7 (52.94)
Day 1 RR Interval, 2 hours, n=25, 26	102.0 (61.66)	80.4 (71.51)
Day 14 RR Interval, Predose, n=24, 23	106.0 (73.20)	103.5 (78.48)
Day 14 RR Interval, 1 hour, n=23, 23	92.5 (64.45)	87.7 (63.30)
Day 14 RR Interval, 4 hours, n=23, 23	92.1 (65.93)	63.6 (47.14)
Day 14 RR Interval, 7 hours, n=23, 23	89.6 (63.06)	74.5 (78.18)
Day 14 RR Interval, 12 hours, n=23, 23	94.4 (73.45)	110.3 (101.24)

Adverse Events

	Placebo		FF 100 µg
Time Frame
Adverse Event Reporting Description

Arm/Group Title	Placebo		FF 100 µg
Arm/Group Description	All participants who received matching placebo in one or both of the two 14-day treatment periods. Matching placebo was administered once daily in the morning (Day 1 to Day 14) via the Dry Powder Inhaler. The washout period between the treatment periods was at least 7 days.		All participants who received FF 100 µg in one or both of the 14-day treatment periods. Inhaled 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.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		FF 100 µg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		FF 100 µg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/25 (16%)		8/26 (30.8%)
Gastrointestinal disorders
Abdominal discomfort	1/25 (4%)		0/26 (0%)
Dyspepsia	0/25 (0%)		1/26 (3.8%)
Toothache	1/25 (4%)		1/26 (3.8%)
General disorders
Product taste abnormal	1/25 (4%)		1/26 (3.8%)
Pyrexia	0/25 (0%)		1/26 (3.8%)
Infections and infestations
Upper respiratory tract infection	1/25 (4%)		1/26 (3.8%)
Acute tonsillitis	0/25 (0%)		1/26 (3.8%)
Influenza	0/25 (0%)		1/26 (3.8%)
Otitis externa	0/25 (0%)		1/26 (3.8%)
Otitis media	0/25 (0%)		1/26 (3.8%)
Tooth abscess	0/25 (0%)		1/26 (3.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/25 (4%)		0/26 (0%)
Nervous system disorders
Headache	0/25 (0%)		3/26 (11.5%)
Respiratory, thoracic and mediastinal disorders
Cough	0/25 (0%)		1/26 (3.8%)
Nasal congestion	0/25 (0%)		1/26 (3.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/Title	GSK Response Center
Organization	GlaxoSmithKline
Phone	866-435-7343
Email

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT01332292

Other Study ID Numbers:

102942

First Posted:

Apr 11, 2011

Last Update Posted:

Mar 23, 2017

Last Verified:

Feb 1, 2017

Pharmacokinetics and PharmacoDynamics of GW685698 in Paedeatric Asthmatic Patients

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