Trial Outcomes & Findings for Inhaled Fluticasone Furoate/Vilanterol Safety and Tolerability, PK and PD Study (NCT NCT01453023)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

26 participants

Primary outcome timeframe

From the start of study medication until Week 11 (Visit 9)/Early Withdrawal

Results posted on

2017-01-11

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	FF 100 µg/VI 25 µg in TP 1 and FF 100 µg in TP 2 Participants received fluticasone furoate (FF) 100 micrograms (µg)/Vilanterol (VI) 25 µg in Treatment Period 1 and FF 100 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.	FF 100 µg in TP 1 and FF 100 µg/VI 25 µg in TP 2 Participants received 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.
Treatment Period (TP) 1 STARTED	13	13
Treatment Period (TP) 1 COMPLETED	12	12
Treatment Period (TP) 1 NOT COMPLETED	1	1
Washout Period STARTED	12	12
Washout Period COMPLETED	12	12
Washout Period NOT COMPLETED	0	0
Treatment Period 2 STARTED	12	12
Treatment Period 2 COMPLETED	12	11
Treatment Period 2 NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	FF 100 µg/VI 25 µg in TP 1 and FF 100 µg in TP 2 Participants received fluticasone furoate (FF) 100 micrograms (µg)/Vilanterol (VI) 25 µg in Treatment Period 1 and FF 100 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.	FF 100 µg in TP 1 and FF 100 µg/VI 25 µg in TP 2 Participants received 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.
Treatment Period (TP) 1 Protocol Violation	1	0
Treatment Period (TP) 1 Met Protocol-defined Stopping Criteria	0	1
Treatment Period 2 Protocol Violation	0	1

Baseline Characteristics

Inhaled Fluticasone Furoate/Vilanterol Safety and Tolerability, PK and PD Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FF 100 µg/VI 25 µg and FF 100 µg in TPs 1 and 2 n=26 Participants 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.
Age, Continuous	8.1 Years STANDARD_DEVIATION 1.97 • n=5 Participants
Gender Female	11 Participants n=5 Participants
Gender Male	15 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	3 Participants n=5 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	1 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	21 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage & White	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period Any AE	4 Participants	1 Participants
Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period Any SAE	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
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	0.025 10^9 cells per liter (GI/L) Standard Deviation 0.0153
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	0.293 10^9 cells per liter (GI/L) Standard Deviation 0.3957
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	2.339 10^9 cells per liter (GI/L) Standard Deviation 0.7391
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	0.222 10^9 cells per liter (GI/L) Standard Deviation 0.1375
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 2.4090	3.106 10^9 cells per liter (GI/L) Standard Deviation 1.3526
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	299.0 10^9 cells per liter (GI/L) Standard Deviation 73.66
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	5.98 10^9 cells per liter (GI/L) Standard Deviation 1.897

PRIMARY outcome

Timeframe: 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.

Blood samples were collected for the measurement of hemoglobin and MCHC at Day 14 of the respective treatment period.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
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	128.0 Grams per liter (g/L) Standard Deviation 6.52
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	330.8 Grams per liter (g/L) Standard Deviation 7.88

PRIMARY outcome

Timeframe: 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.

Blood samples were collected for the measurement of reticulocytes and RBCs at Day 14 of the respective treatment period.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
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	4.38 10^12 cells per liter (TI/L) Standard Deviation 0.199
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	0.07323 10^12 cells per liter (TI/L) Standard Deviation 0.032203

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=21 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=23 Participants 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.
Hematocrit Values at Day 14 of the Respective Treatment Period	0.3816 proportion of 1 Standard Deviation 0.04199	0.3866 proportion of 1 Standard Deviation 0.02160

PRIMARY outcome

Timeframe: 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.

Blood samples were collected for the measurement of MCV at Day 14 of the respective treatment period.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=21 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=23 Participants 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.
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	88.6 10^15 femtoliters (fL) per cell Standard Deviation 3.37

PRIMARY outcome

Timeframe: 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.

Blood samples were collected for the measurement of MCH at Day 14 of the respective treatment period.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=21 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=23 Participants 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.
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	29.25 10^12 picograms (pg) per cell Standard Deviation 1.116

PRIMARY outcome

Timeframe: 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.

Blood samples were collected for the measurement of ALT, ALP, AST, and GGT at Day 14 of the respective treatment period.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
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	16.1 International units per liter (IU/L) Standard Deviation 10.36
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	17.7 International units per liter (IU/L) Standard Deviation 14.88
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	272.6 International units per liter (IU/L) Standard Deviation 119.48
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	29.0 International units per liter (IU/L) Standard Deviation 7.51

PRIMARY outcome

Timeframe: 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.

Blood samples were collected for the measurement of albumin and total protein at Day 14 of the respective treatment period.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
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	45.6 Grams per liter Standard Deviation 2.20
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	70.4 Grams per liter Standard Deviation 3.12

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
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	2.415 Millimoles per liter (mmol/L) Standard Deviation 0.0749
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	103.8 Millimoles per liter (mmol/L) Standard Deviation 1.79
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	19.1 Millimoles per liter (mmol/L) Standard Deviation 2.05
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	4.53 Millimoles per liter (mmol/L) Standard Deviation 0.523
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	4.27 Millimoles per liter (mmol/L) Standard Deviation 0.265
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	139.0 Millimoles per liter (mmol/L) Standard Deviation 1.85
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	4.52 Millimoles per liter (mmol/L) Standard Deviation 1.108

PRIMARY outcome

Timeframe: 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.

Blood samples were collected for the measurement of total bilirubin, direct bilirubin, creatinine, and uric acid at Day 14 of the respective treatment period.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
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	5.9 Micromoles per liter (µmol/L) Standard Deviation 1.72
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 0.70	1.9 Micromoles per liter (µmol/L) Standard Deviation 0.41
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	37.09 Micromoles per liter (µmol/L) Standard Deviation 6.225
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	233.8 Micromoles per liter (µmol/L) Standard Deviation 54.04

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
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	223.6 liters/minute Standard Deviation 56.91
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	223.0 liters/minute Standard Deviation 55.15
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 53.50	228.2 liters/minute Standard Deviation 56.73
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	227.2 liters/minute Standard Deviation 54.07
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	228.6 liters/minute Standard Deviation 54.17
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	215.0 liters/minute Standard Deviation 50.71
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	218.1 liters/minute Standard Deviation 52.12
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	225.8 liters/minute Standard Deviation 48.78
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	230.4 liters/minute Standard Deviation 52.54

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
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	88.6 Beats per minute Standard Error 1.63
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	85.7 Beats per minute Standard Error 1.67

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
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	402.2 milliseconds Standard Error 1.98
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	404.2 milliseconds Standard Error 2.02

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=24 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=24 Participants 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.
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 picogramshour per milliliter (pghr/mL) Interval 21.63 to 69.941	32.880 picogramshour per milliliter (pghr/mL) Interval 18.268 to 59.179
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 picogramshour per milliliter (pghr/mL) Interval 70.03 to 105.96	83.83 picogramshour per milliliter (pghr/mL) Interval 71.49 to 98.3

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=23 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=24 Participants 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.
Cmax of FF on Day 14 of the Respective Treatment Period	20.73 picograms per milliliter (pg/mL) Interval 15.16 to 28.36	21.16 picograms per milliliter (pg/mL) Interval 14.91 to 30.02

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=24 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=24 Participants 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.
Tmax and Tlast of FF on Day 14 of the Respective Treatment Period tmax, n=20, 19	0.965 hours Interval 0.0 to 2.07	0.500 hours Interval 0.0 to 3.95
Tmax and Tlast of FF on Day 14 of the Respective Treatment Period tlast, n=20, 19	4.030 hours Interval 0.52 to 4.13	4.020 hours Interval 1.03 to 4.05

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=23 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg 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.
AUC(0-t) and AUC(0-4) of VI on Day 14 of the Respective Treatment Period AUC(0-t), n=23	44.297 picogramshour per milliliter (pghr/mL) Interval 26.996 to 72.688	—
AUC(0-t) and AUC(0-4) of VI on Day 14 of the Respective Treatment Period AUC(0-4), n=11	119.19 picogramshour per milliliter (pghr/mL) Interval 102.41 to 138.73	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=23 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg 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.
Cmax of VI on Day 14 of the Respective Treatment Period	44.21 picograms per milliliter (pg/mL) Interval 27.65 to 70.7	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=23 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg 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.
Tmax and Tlast of VI on Day 1 of the Respective Treatment Period tmax, n=21	0.170 hours Interval 0.0 to 2.08	—
Tmax and Tlast of VI on Day 1 of the Respective Treatment Period tlast, n=21	3.870 hours Interval 0.5 to 4.13	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
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 • Interval 5.275 to 5.881	5.074 Millimoles per liter (mmol/L) 95% Confidence Interval 0.1443 • Interval 4.781 to 5.367
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 • Interval 3.969 to 4.15	4.148 Millimoles per liter (mmol/L) 95% Confidence Interval 0.0426 • Interval 4.062 to 4.234

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=23 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=23 Participants 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.
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 • Interval 168.42 to 222.93	192.50 nanomoles per Liter 95% Confidence Interval 0.069 • Interval 167.32 to 221.48

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
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 2.010	3.85 centimeters squared (cm^2) Standard Deviation 2.043
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	3.70 centimeters squared (cm^2) Standard Deviation 2.279

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
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	19.24 centimeters (cm) Standard Deviation 0.959
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	19.10 centimeters (cm) Standard Deviation 1.003

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
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	75.54 Liters per minute (L/min) Standard Deviation 44.195
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	71.47 Liters per minute (L/min) Standard Deviation 45.841

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
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	42.72 Liters per minute (L/min) Standard Deviation 11.593
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	41.36 Liters per minute (L/min) Standard Deviation 10.354
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	67.60 Liters per minute (L/min) Standard Deviation 16.097
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	64.79 Liters per minute (L/min) Standard Deviation 15.886

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
Inhalation Time on Days 1 and 14 of of the Respective Treatment Period Day 1, n=23, 23	0.97 Seconds (sec) Standard Deviation 0.350	0.83 Seconds (sec) Standard Deviation 0.385
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	0.91 Seconds (sec) Standard Deviation 0.347

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
Inhaled Volume on Days 1 and 14 of the Respective Treatment Period Day 1, n=23, 23	0.69 Liters Standard Deviation 0.337	0.58 Liters Standard Deviation 0.285
Inhaled Volume on Days 1 and 14 of the Respective Treatment Period Day 14, n=23, 23	0.68 Liters Standard Deviation 0.308	0.65 Liters Standard Deviation 0.352

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
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	3.97 Kilopascal (kpa) Standard Deviation 1.787
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	3.67 Kilopascal (kpa) Standard Deviation 1.611

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
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	86.33 micrograms Standard Deviation 1.505
Total Emitted Dose (TED) on Day 14 of the Respective Treatment Period Minimum TED FF, n=23, 23	87.64 micrograms Standard Deviation 0.330	86.72 micrograms Standard Deviation 1.589
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	85.93 micrograms Standard Deviation 1.534
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	NA micrograms Standard Deviation NA The TED of VI was not assessed in participants receiving only FF.
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	NA micrograms Standard Deviation NA The TED of VI was not assessed in participants receiving only FF.
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	NA micrograms Standard Deviation NA The TED of VI was not assessed in participants receiving only FF.

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
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	24.34 micrograms Standard Deviation 8.574
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	22.99 micrograms Standard Deviation 9.120
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	25.48 micrograms Standard Deviation 8.197
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	5.97 micrograms Standard Deviation 1.382
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	5.77 micrograms Standard Deviation 1.319
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	6.21 micrograms Standard Deviation 1.476
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	NA micrograms Standard Deviation NA The ETD of VI was not assessed in participants receiving only FF.
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	NA micrograms Standard Deviation NA The ETD of VI was not assessed in participants receiving only FF.
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	NA micrograms Standard Deviation NA The ETD of VI was not assessed in participants receiving only FF.
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	NA micrograms Standard Deviation NA The ETD of VI was not assessed in participants receiving only FF.
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	NA micrograms Standard Deviation NA The ETD of VI was not assessed in participants receiving only FF.
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	NA micrograms Standard Deviation NA The ETD of VI was not assessed in participants receiving only FF.

Adverse Events

FF 100 µg/VI 25 µg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

FF 100 µg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	FF 100 µg/VI 25 µg n=25 participants at risk Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 participants at risk 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.
Infections and infestations Bronchitis	4.0% 1/25 Serious adverse events (SAEs) and non-serious AEs were collected in members of the All Subjects Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/25 Serious adverse events (SAEs) and non-serious AEs were collected in members of the All Subjects Population, comprised of all participants who received at least one dose of study medication.
Infections and infestations Conjunctivitis viral	0.00% 0/25 Serious adverse events (SAEs) and non-serious AEs were collected in members of the All Subjects Population, comprised of all participants who received at least one dose of study medication.	4.0% 1/25 Serious adverse events (SAEs) and non-serious AEs were collected in members of the All Subjects Population, comprised of all participants who received at least one dose of study medication.
Infections and infestations Pharyngitis streptococcal	4.0% 1/25 Serious adverse events (SAEs) and non-serious AEs were collected in members of the All Subjects Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/25 Serious adverse events (SAEs) and non-serious AEs were collected in members of the All Subjects Population, comprised of all participants who received at least one dose of study medication.
Infections and infestations Upper respiratory tract infection	0.00% 0/25 Serious adverse events (SAEs) and non-serious AEs were collected in members of the All Subjects Population, comprised of all participants who received at least one dose of study medication.	4.0% 1/25 Serious adverse events (SAEs) and non-serious AEs were collected in members of the All Subjects Population, comprised of all participants who received at least one dose of study medication.
Eye disorders Conjunctivitis	4.0% 1/25 Serious adverse events (SAEs) and non-serious AEs were collected in members of the All Subjects Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/25 Serious adverse events (SAEs) and non-serious AEs were collected in members of the All Subjects Population, comprised of all participants who received at least one dose of study medication.
Nervous system disorders Headache	4.0% 1/25 Serious adverse events (SAEs) and non-serious AEs were collected in members of the All Subjects Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/25 Serious adverse events (SAEs) and non-serious AEs were collected in members of the All Subjects Population, comprised of all participants who received at least one dose of study medication.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	FF 100 µg/VI 25 µg n=25 Participants Participants received FF 100 µg/VI 25 µg in one of the two 14-day treatment periods. FF 100 µg/VI 25 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.	FF 100 µg n=25 Participants 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.
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	99.9 Millimeters of mercury (mmHg) Standard Deviation 6.71
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	-0.1 Millimeters of mercury (mmHg) Standard Deviation 4.66
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	0.4 Millimeters of mercury (mmHg) Standard Deviation 3.70
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	1.3 Millimeters of mercury (mmHg) Standard Deviation 2.95
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	-1.2 Millimeters of mercury (mmHg) Standard Deviation 6.92
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	-1.2 Millimeters of mercury (mmHg) Standard Deviation 6.03
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	-0.8 Millimeters of mercury (mmHg) Standard Deviation 6.36
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	-0.8 Millimeters of mercury (mmHg) Standard Deviation 6.34
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	0.1 Millimeters of mercury (mmHg) Standard Deviation 6.47
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	-0.4 Millimeters of mercury (mmHg) Standard Deviation 7.17
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	63.6 Millimeters of mercury (mmHg) Standard Deviation 3.86
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	-0.3 Millimeters of mercury (mmHg) Standard Deviation 3.76
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	0.8 Millimeters of mercury (mmHg) Standard Deviation 3.11
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	1.0 Millimeters of mercury (mmHg) Standard Deviation 3.38
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	0.2 Millimeters of mercury (mmHg) Standard Deviation 3.29
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	0.1 Millimeters of mercury (mmHg) Standard Deviation 2.62
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	0.0 Millimeters of mercury (mmHg) Standard Deviation 2.30
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	0.4 Millimeters of mercury (mmHg) Standard Deviation 3.19
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	1.1 Millimeters of mercury (mmHg) Standard Deviation 3.35
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	-0.2 Millimeters of mercury (mmHg) Standard Deviation 3.02