A 3-period Crossover Study With GSK573719 as Monotherapy in Adult Subjects With Asthma

A Multi-national, Randomized, Double-blind, Placebo-controlled, 3-period Crossover Study With GSK 573719 as Monotherapy in Adult Subjects With Asthma

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01641692

Enrollment

350

Registered

2012-07-17

Start date

2012-05-31

Completion date

2013-02-28

Last updated

2017-03-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Asthma

Keywords

Asthma, Pharmacokinetics, GSK573719, Adults, Pharmacogenetics

Brief summary

This is a multi-national, randomized, double-blind, 3-period crossover, incomplete block design to evaluate 5 once-daily and 2 twice-daily doses of GSK573719 in combination with placebo. The study will explore the dose range of GSK573719 in asthmatic subjects who are currently using non-ICS controller medications. Subjects will participate in the study for up to a maximum of 14 weeks. At randomization subjects will be stratified by age to ensure adequate exposure to GSK573719 throughout the expected age range. The primary endpoint will be trough FEV1 obtained 24 hours after the last morning dose on Day 14 of each treatment sequence. A sub-group of subjects at selected sites (approximately 30% of the total population) will have additional serial assessments for spirometry, ECG and Holter, and pharmacokinetic sampling at the start and end of each treatment period. Safety assessments will include monitoring for adverse events, laboratory tests, asthma symptom assessments and twice daily PEF evaluation. Consenting subjects will have a blood sample taken for pharmacogenetic analysis.

Detailed description

Asthma, a reversible obstructive disease of the airways, is defined as a chronic inflammatory disorder of the airways in which many of the cells and cellular mediators play a role. The chronic inflammation is associated with airway hyper-responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or early in the morning. These episodes are usually associated with widespread, but variable airflow obstruction within the lung that is often reversible either spontaneously or with treatment (NIH 2007, GINA, 2010,). Guidelines recommend a stepwise approach to the management of asthma. For many patients with mild disease, asthma symptoms can be adequately relieved by 'on demand' use of a short acting beta-2 -agonist (SABA) alone. A long-acting, inhaled, muscarinic receptor antagonist (LAMA) exerts its effects via distinct and complementary bronchodilator mechanisms on large and small airways through antagonism of the endogenous agonist acetylcholine at the muscarinic receptors leading to smooth muscle relaxation and bronchodilation. However, most experience with older anti-cholinergics has been with acute use and little is known about their effect in chronic use or as maintenance in asthma. Newer more selective muscarinic receptor antagonists are being developed for chronic use which appear to have a better adverse event profile compared with older anti-cholinergics in the treatment of asthma \[Moulton 2011\]. A once daily long-acting, inhaled, muscarinic receptor antagonist (LAMA) bronchodilator, GSK573719, may offer an alternative treatment option to patients with asthma. The proposed study is a multi-national, randomized, double-blind, 3-period crossover, incomplete block study in outpatient subjects with mild asthma and who are not using inhaled corticosteroids (ICS) for symptom control. The primary objective of this study is to evaluate the dose response, efficacy and safety of five once-daily doses of GSK573719 compared with placebo, over a 14-day treatment period, in patients with asthma. A placebo arm will be included to determine an absolute treatment effect over placebo for each GSK573719 dose regimen. Each eligible subject will be randomized to receive 3 out of 8 potential treatments in sequence over a total of three 14-day treatment periods. There will be 12 clinic visits including a safety follow-up visit at the end of the study. All subjects will be provided with albuterol (salbutamol) for use on an 'as-needed' basis throughout the run-in, treatment and washout periods. A sub-group (approximately 30%) of the study population will comprise subjects from selected sites. These subjects will have additional assessments at the start and end of each treatment period, including serial spirometry, serial ECGs, 24 hour Holter monitoring, and samples of blood and urine for pharmacokinetic analysis. Other safety parameters include the incidence of adverse events, vital signs, clinical laboratory parameters, ECGs and spirometry, including twice daily peak expiratory flow, asthma exacerbation assessment. and use of salbutamol.

Interventions

DRUGGSK573719 Active treatment or Placebo

Eligible subjects will be randomised to a sequence of three treatments from 8 possible arms: 7 active drug doses (15.6mcg, 31.25 mc, 62.5mcg 125mcg or 250mcg GSK573719 once daily; 15.6mcg or 31.25 mcg GSK573719 taken twice daily) or matched placebo.

PROCEDUREGSK573719 (Sub-group cohort)

Subjects at selected Sub-group sites (approximately 30% of the total population) will have additional serial assessments and procedures (including blood and urine samples for pharmacokinetic analysis) at the start (Day 1) and at the end (Days 14 and 15) of each treatment period. On Day 14 of each treatment period subjects will remain overnight at the clinic for 24-hour assessments, including spirometry, ECGs, and 24-hour Holter monitoring.

DRUGSalbutamol/Albuterol

Salbutamol/Albuterol, short-activing beta agonist provided to all subjects to be taken as needed for the relief of asthma symptoms.throughout the study period, including washout periods

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Written informed consent * Outpatient (sub-group will have 3 overnight stays at clinic) * Diagnosis of asthma (NIH 2007) for at least 6 months * Male or Eligible female (females of child-bearing potential must use acceptable method of birth control) * A best AM pre-bronchodilator FEV1 of 60% to 85% of predicted normal value at Screening * Reversibility of disease demonstrated by at least 12% and 200mL increase in FEV1 . * Subjects must have been prescribed a non-corticosteroid controller at least 3 months preceding Visit 1, and/or a short-acting beta 2 agonist, without the use of inhaled corticosteroids in the 4 weeks prior to Visit 1 * Subjects must be able to replace their current short-acting Beta-2-agonist with albuterol/salbutamol aerosol inhaler for the duration of the study * Subjects must be judged capable of withholding albuterol/salbutamol for at least 4 hours prior to study visits

Exclusion criteria

* History of life threatening asthma * Severe asthma exacerbation * Respiratory infection within expected to affect subject's ability to participate * Concurrent respiratory disease * Current smoker or smoking history of 10 pack years or more * Diseases preventing use of anticholinergics * Other clinically significant, uncontrolled condition or disease which would pose a safety risk to the patient, or confound interpretation of study results * Drug allergy to any Beta-2-agonist, sympathomimetic drug, intranasal, inhaled or systemic corticosteroid therapy * Known or suspected sensitivity to the constituents of the Novel DPI (ie lactose) * History of severe milk protein allergy * Administration of prescription or over-the-counter medication that would significantly affect the course of asthma, or interact with the study drug * Any infirmity, disability or disease of a child or family member likely to impair compliance * Alcohol or substance abuse history * Viral hepatitis B surface antigen or Hepatitis C antibody * Known HIV-positive history. * Affiliation with investigator or site staff

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With the Indicated 24 Hour Holter Findings	Day 14 of each treatment period (up to Study Day 70)	Twenty-four hour Holter ECG measurements were obtained using a 12-lead Holter monitor. The Holter monitor is worn by the participant for 24 hours, and the monitor continuously records the heart's rhythm while the monitor is worn. Following the 24-hour period, the data from the monitor were downloaded and transmitted to the centralized vendor for analysis and interpretation by a licensed cardiologist. The 24-hour Holter ECG measurements were obtained at during the screening period and on Day 14 of each treatment period. The number of participants with clinically significant change (abnormal or normal) were reported.
Change From Baseline in Hematocrit on Day 14 of Each Treatment Period	Baseline and Day 14 of each treatment period (up to Study Day 70)	Blood samples were collected for the measurement of hematocrit (proportion of red blood cells in blood) at Baseline and Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	Baseline and Day 14 of each treatment period (up to Study Day 70))	Urinalysis parameters included: Urine Bilirubin (UB), Urine Occult Blood (UOB), Urine Glucose (UG), Urine Ketones (UK), Urine Nitrite (UN), Urine Protein (UP), and Urine Leukocyte Esterase test for detecting White Blood Cell (UWBC). The dipstick was a strip used to detect the presence or absence of these parameters in the urine sample. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative (Neg), Trace (T), 1+, 2+, and 3+, and for UG the result can be read as Neg, T, T or 1/10 G/dL, 1+ or 1/4 G/dL, 3+ or 1 G/dL, indicating proportional concentrations in the urine sample. Data are reported as the number of participants who had neg, T, 1+, 2+ and 3+ levels at Day 14.
Urine pH on Day 14 of Each Treatment Period	Day 14 of each treatment period (up to Study Day 70)	Urine samples were collected for the measurement of urine pH by dipstick method at Day 14. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).
Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Day 14 of each treatment period (up to Study Day 70)	Electrocardiograph measurements performed at Screening (Visit 1) and at Day 1 and Day 14 (pre-dose, 10 minutes post-dose and 2 hours post-dose.of each treatment period). Any clinically significant findings were identified during participant monitoring.
Final Dose-response Model for Trough Forced Expiratory Volume in One Second (FEV1)	Day 15 of each treatment period (up to Study Day 71)	Dose-response was conducted for both QD and BID UMEC doses on trough FEV1 (measure of lung function, defined as the maximal amount of air that can be forcefully exhaled in 1 second) on D 15. Total daily dose of UMEC was used in the modeling. The null model was the final model. The null model is defined as: CFEV1,ij=(THETA1+ETA1j)\meanBL+(THETA2+ETA1j)\periodBL+EPSij, where CFEV1,ij represents the change from BL in trough FEV1 for participant j measured at period i. THETA1 and THETA2 were the slopes with respect to meanBL and periodBL, respectively. Omegas were the variance of the slopes on meanBL and periodBL (ETA1j, ETA2j) for each participant and Sigma was the variance of the residual errors (EPSij). MeanBL is the mean of the Baseline (BL) which is the FEV1 value recorded pre-dose on D 1 of each TP; periodBL is the difference between the BL and the meanBL in each TP for each participant.
Change From Baseline in Trough FEV1 on Day 15 of Each Treatment Period	Day 15 of each treatment period (up to Study Day 71)	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on Treatment Day 15 is defined as the value obtained 24 hours after the morning dose administered on Day 14. Analysis was performed using a mixed model, including treatment, period, period Baseline FEV1 and mean Baseline FEV1 as fixed effects and participant as a random effect. Baseline is the FEV1 value recorded pre-dose on Day 1 of each treatment period; mean Baseline is the mean of the Baselines for each participant and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Change from Baseline for each treatment period is the trough FEV1 at Day 15 minus the Baseline value for that treatment period.
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)	From Baseline until the end of Treatment Period 3 (up to Study Day 70)	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An 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, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of SAEs.
Number of Participants With Asthma Exacerbations During the Treatment Period	From Baseline until the end of Treatment Period 3 (up to Study Day 70)	Worsening of asthma symptoms is monitored throughout the study. Severe exacerbation (deterioration of asthma requiring use of systemic corticosteroids for 3 days, inpatient hospitalization or emergency department visit due to asthma) is an exclusion criterion and requires withdrawal from the study. Asthma symptoms were assessed daily using an electronic diary throughout study.
Change From Baseline in Systolic Blood Pressure on Day 14 of Each Treatment Period	Baseline and Day 14 of each treatment period (up to Study Day 70)	Blood pressure measurement included systolic blood pressure (SBP). Blood pressure was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Analysis was performed using a mixed model, including treatment, period, period Baseline and mean Baseline for the measure as fixed effects and participant as a random effect. Baseline is the value recorded pre-dose on Day 1 of each treatment period; mean Baseline is the mean of the Baselines for each participant and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Change from Baseline was calculated as the assessment value at Day 14 minus the Baseline value.
Change From Baseline in Diastolic Blood Pressure on Day 14 of Each Treatment Period	Baseline and Day 14 of each treatment period (up to Study Day 70)	Blood pressure measurement included diastolic blood pressure (DBP). Blood pressure was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Analysis was performed using a mixed model, including treatment, period, period Baseline and mean Baseline for the measure as fixed effects and participant as a random effect. Baseline is the value recorded pre-dose on Day 1 of each treatment period; mean Baseline is the mean of the Baselines for each participant and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Change from Baseline was calculated as the assessment value at Day 14 minus the Baseline value.
Change From Baseline in Pulse Rate on Day 14 of Each Treatment Period	Baseline and Day 14 of each treatment period (up to Study Day 70)	Pulse rate was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Analysis was performed using a mixed model, including treatment, period, period Baseline and mean Baseline for the measure as fixed effects and participant as a random effect. Baseline is the value recorded pre-dose on Day 1 of each treatment period; mean Baseline is the mean of the Baselines for each participant and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Change from Baseline was calculated as the assessment value at Day 14 minus the Baseline value.
Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Baseline and Day 14 of each treatment period (up to Study Day 70))	Blood samples were collected for the measurement of albumin, total protein, and hemoglobin at Baseline and Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	Baseline and Day 14 of each treatment period (up to Study Day 70)	Blood samples were collected for the measurement of ALP, ALT, AST, CK, GGT, and LDH at Baseline and Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Baseline and Day 14 of each treatment period (up to Study Day 70)	Blood samples were collected for the measurement of direct bilirubin, indirect (ind) bilirubin, total bilirubin, and creatinine at Baseline and Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Urine Specific Gravity on Day 14 of Each Treatment Period	Day 14 of each treatment period (up to Study Day 70)	Urine samples were collected for the measurement of urine specific gravity by dipstick method at Day 14. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. A urinary specific gravity measurement is a routine part of urinalysis. The reference range is 1.002-1.030.
Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Baseline and Day 14 of each treatment period (up to Study Day 70)	Blood samples were collected for the measurement of chloride, caron dioxide, glucose, potassium, sodium, and urea/BUN at Baseline and Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Baseline and Day 14 of each treatment period (up to Study Day 70)	Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils (ANC - Absolute neutrophil \[neut\] count), platelet, and leucocytes count at Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Baseline and Day 14 of each treatment period (up to Study Day 70)	Blood samples were collected for the measurement of the percentage of basophils, eosinophils, lymphocytes, monocytes, and segmented neutrophils (neut) at Baseline and Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Secondary

Measure	Time frame	Description
Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	Baseline and Day 14 of each treatment period (up to Study Day 70)	Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry. Serial FEV1 was measured at 5, 15, 30 minutes (min), 1, 3, 6, 9, 12, 16, 20, 23 and 24 hours (h) post-dose. Baseline is the 0h value obtained prior to the AM dose on Day 14 of the treatment period. Change from Baseline was calculated as FEV1 value at the evaluated time point minus Baseline. Analysis was preformed using a repeated measures model with terms for period, treatment, time, mean Baseline, period Baseline, and time by mean Baseline, time by period Baseline, and time by treatment interactions.
Change From Baseline in Mean Morning (AM) and Evening (PM) Pre-treatment Peak Expiratory Flow (PEF) Over Day 7 to Day 14 of Each Treatment Period	Baseline (Day 7 prior to each treatment period) and the last 7 days of each treatment period (up to Study Day 70)	PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants daily in the morning and evening just prior to each dose, using an electronic peak flow meter, throughout the 14-day Treatment Period. Only the averaged daily AM and PM PEF over Days 7 to 14 was analyzed. The analysis was performed using a mixed effects analysis of covariance model with fixed effect terms for treatment and period; Baseline PEF AM and PM, gender and age fitted as covariates; and participant as a random effect.
Change From Baseline in the Mean Number of Puffs Per Day of Rescue Albuterol/Salbutamol Over Day 7 to Day 14 of Each Treatment Period	Baseline (Day 7 prior to each treatment period) and the last 7 days of each treatment period (up to Study Day 70)	The mean number of puffs per day of rescue salbutamol at Baseline (i.e. run-in or washout data) and on-treatment were recorded. Total puffs was calculated as (Number of Puffs + (2 x number of Nebules)). Only the 7 days proceeding each treatment period were included in the Baseline calculations. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change From Baseline (BL) in the Weighted Mean (WM) 0-24 Hour FEV1 Obtained Post-AM Dose on Day 14 of Each Treatment Period	Baseline and Day 14 of each treatment period (up to Study Day 70)	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The WM FEV1 was derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. Baseline is the 0h value obtained prior to the AM dose on Day 14 of the treatment period. Change from BL at a was calculated as WM at the evaluated time point minus BL. Analysis was performed using a mixed model, including treatment, period, period Baseline FEV1, and mean Baseline FEV1 as fixed effects and participant as a random effect.

Countries

Bulgaria, Germany, Mexico, Peru, Poland, United States

Participant flow

Pre-assignment details

Participants were randomized to receive a sequence of 3 of 8 possible treatments over 3 treatment periods. There are 56 combinations of 3 treatments from the 8 study treatments, each of which can be ordered in 6 ways (totaling 336 possible sequences; 246 were randomly assigned). Participant Flow data are presented by treatment rather than sequence.

Participants by arm

Arm	Count
All Study Treatments The treatment phase was comprised of three 14-day treatment periods. Treatment Period 1 and 2 were followed by a 12-14 day washout period. Treatment Period 3 was followed by a 5 to 9 day washout period before the Follow-up visit. Participants were randomly assigned to receive a sequence of 3 of the 8 active treatments : UMEC 15.6, 31.25, 62.5, 125, 250 µg QD and UMEC 15.6, 31.25 µg BID, placebo.	350
Total	350

Arm

Count

All Study Treatments

The treatment phase was comprised of three 14-day treatment periods. Treatment Period 1 and 2 were followed by a 12-14 day washout period. Treatment Period 3 was followed by a 5 to 9 day washout period before the Follow-up visit. Participants were randomly assigned to receive a sequence of 3 of the 8 active treatments : UMEC 15.6, 31.25, 62.5, 125, 250 µg QD and UMEC 15.6, 31.25 µg BID, placebo.

350

Total

350

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007
Treatment Period 1	Adverse Event	1	0	0	0	0	0	0	0
Treatment Period 1	Lack of Efficacy	0	0	0	0	0	0	0	1
Treatment Period 1	Lost to Follow-up	0	0	1	0	0	0	0	0
Treatment Period 1	Physician Decision	0	0	0	0	1	0	0	0
Treatment Period 1	Protocol-defined Stopping Criteria	0	0	0	0	1	0	0	1
Treatment Period 1	Protocol Violation	1	0	0	0	2	0	0	0
Treatment Period 1	Withdrawal by Subject	0	0	0	0	0	2	0	1
Treatment Period 2	Lack of Efficacy	1	0	0	0	0	0	0	0
Treatment Period 2	Lost to Follow-up	0	0	0	0	0	1	0	0
Treatment Period 2	Protocol-defined Stopping Criteria	1	0	0	0	0	0	0	0
Treatment Period 2	Withdrawal by Subject	1	0	0	0	0	1	0	1
Treatment Period 3	Adverse Event	0	0	0	0	0	0	1	0
Treatment Period 3	Lost to Follow-up	0	1	0	0	0	0	0	0
Treatment Period 3	Protocol-defined Stopping Criteria	0	0	0	0	0	0	1	0
Treatment Period 3	Protocol Violation	0	0	1	0	0	0	0	0
Washout Period 1 (12-14 Days)	Adverse Event	2	0	0	0	0	0	0	0
Washout Period 1 (12-14 Days)	Protocol-defined Stopping Criteria	1	0	3	1	3	0	0	1
Washout Period 1 (12-14 Days)	Protocol Violation	0	0	0	0	0	0	1	0
Washout Period 1 (12-14 Days)	Withdrawal by Subject	1	1	0	1	1	0	1	0
Washout Period 2 (12-14 Days)	Protocol-defined Stopping Criteria	0	0	0	0	3	0	1	0
Washout Period 2 (12-14 Days)	Withdrawal by Subject	0	0	1	0	0	1	0	1
Washout Period 3 or Follow-up	Protocol-defined Stopping Criteria	1	0	1	1	0	1	1	0
Washout Period 3 or Follow-up	Protocol Violation	0	0	0	0	0	1	0	0

Baseline characteristics

Characteristic	All Study Treatments
Age, Continuous	42.6 Years STANDARD_DEVIATION 14.84
Race/Ethnicity, Customized African American/African Heritage (HER)	33 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	85 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native & White	31 Participants
Race/Ethnicity, Customized Asian-Japanese/East Asian HER/South East Asian HER	4 Participants
Race/Ethnicity, Customized White	197 Participants
Sex: Female, Male Female	232 Participants
Sex: Female, Male Male	118 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	4 / 126	7 / 131	7 / 138	12 / 133	11 / 128	12 / 135	7 / 126	7 / 133
serious Total, serious adverse events	0 / 126	0 / 131	0 / 138	0 / 133	0 / 128	1 / 135	0 / 126	0 / 133

Outcome results

Primary

Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period

Blood samples were collected for the measurement of albumin, total protein, and hemoglobin at Baseline and Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Time frame: Baseline and Day 14 of each treatment period (up to Study Day 70))

Population: ITT Population. Only those participants remaining in the study and contributing evaluable data for the indicated parameter were indicated by n=X, X in the category title and the overall number of participants analyzed reflects everyone in the ITT Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
All Study Treatments	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Albumin, n=111, 118, 120, 121, 112, 112, 112, 117	-1.1 Grams per liter (G/L)	Standard Deviation 2.46
All Study Treatments	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Hemogloin, n=109,121,124,120,110,113,112,121	-2.2 Grams per liter (G/L)	Standard Deviation 7.24
All Study Treatments	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Total protein, n=111,118,120,121,112,112,112,117	-1.9 Grams per liter (G/L)	Standard Deviation 3.63
UMEC 15.6 µg QD	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Hemogloin, n=109,121,124,120,110,113,112,121	-2.8 Grams per liter (G/L)	Standard Deviation 6.55
UMEC 15.6 µg QD	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Total protein, n=111,118,120,121,112,112,112,117	-1.9 Grams per liter (G/L)	Standard Deviation 3.83
UMEC 15.6 µg QD	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Albumin, n=111, 118, 120, 121, 112, 112, 112, 117	-1.0 Grams per liter (G/L)	Standard Deviation 2.63
UMEC 31.25 µg QD	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Hemogloin, n=109,121,124,120,110,113,112,121	-1.6 Grams per liter (G/L)	Standard Deviation 6.66
UMEC 31.25 µg QD	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Albumin, n=111, 118, 120, 121, 112, 112, 112, 117	-0.8 Grams per liter (G/L)	Standard Deviation 2.47
UMEC 31.25 µg QD	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Total protein, n=111,118,120,121,112,112,112,117	-1.4 Grams per liter (G/L)	Standard Deviation 3.82
UMEC 62.5 µg QD	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Albumin, n=111, 118, 120, 121, 112, 112, 112, 117	-0.9 Grams per liter (G/L)	Standard Deviation 2.59
UMEC 62.5 µg QD	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Total protein, n=111,118,120,121,112,112,112,117	-1.7 Grams per liter (G/L)	Standard Deviation 3.48
UMEC 62.5 µg QD	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Hemogloin, n=109,121,124,120,110,113,112,121	-2.3 Grams per liter (G/L)	Standard Deviation 7.13
UMEC 125 µg QD	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Total protein, n=111,118,120,121,112,112,112,117	-1.9 Grams per liter (G/L)	Standard Deviation 4.02
UMEC 125 µg QD	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Albumin, n=111, 118, 120, 121, 112, 112, 112, 117	-1.1 Grams per liter (G/L)	Standard Deviation 2.65
UMEC 125 µg QD	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Hemogloin, n=109,121,124,120,110,113,112,121	-1.8 Grams per liter (G/L)	Standard Deviation 7.44
UMEC 250 µg QD	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Total protein, n=111,118,120,121,112,112,112,117	-1.8 Grams per liter (G/L)	Standard Deviation 3.58
UMEC 250 µg QD	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Albumin, n=111, 118, 120, 121, 112, 112, 112, 117	-1.0 Grams per liter (G/L)	Standard Deviation 2.47
UMEC 250 µg QD	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Hemogloin, n=109,121,124,120,110,113,112,121	-1.4 Grams per liter (G/L)	Standard Deviation 6.76
UMEC 15.6 µg BID	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Total protein, n=111,118,120,121,112,112,112,117	-1.1 Grams per liter (G/L)	Standard Deviation 3.58
UMEC 15.6 µg BID	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Albumin, n=111, 118, 120, 121, 112, 112, 112, 117	-0.6 Grams per liter (G/L)	Standard Deviation 2.41
UMEC 15.6 µg BID	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Hemogloin, n=109,121,124,120,110,113,112,121	-1.3 Grams per liter (G/L)	Standard Deviation 6.59
UMEC 31.25 µg BID	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Albumin, n=111, 118, 120, 121, 112, 112, 112, 117	-0.7 Grams per liter (G/L)	Standard Deviation 2.14
UMEC 31.25 µg BID	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Total protein, n=111,118,120,121,112,112,112,117	-1.2 Grams per liter (G/L)	Standard Deviation 3.09
UMEC 31.25 µg BID	Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period	Hemogloin, n=109,121,124,120,110,113,112,121	-2.0 Grams per liter (G/L)	Standard Deviation 7.06

Primary

Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period

Blood samples were collected for the measurement of ALP, ALT, AST, CK, GGT, and LDH at Baseline and Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Time frame: Baseline and Day 14 of each treatment period (up to Study Day 70)

Arm	Measure	Group	Value (MEAN)	Dispersion
All Study Treatments	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	ALP, n=111, 118, 120, 121, 112, 112, 112, 117	-0.7 International Units/Liter (IU/L)	Standard Deviation 16.13
All Study Treatments	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	GGT, n=111, 118, 120, 121, 112, 112, 112, 117	1.2 International Units/Liter (IU/L)	Standard Deviation 15.06
All Study Treatments	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	CK, n=111, 118, 120, 121, 112, 112, 112, 117	5.2 International Units/Liter (IU/L)	Standard Deviation 69.94
All Study Treatments	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	AST, n=110, 118, 120, 120, 112, 112, 112, 117	0.6 International Units/Liter (IU/L)	Standard Deviation 7.53
All Study Treatments	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	ALT, n=111, 117, 120, 121, 112, 112, 112, 117	0.7 International Units/Liter (IU/L)	Standard Deviation 12.15
UMEC 15.6 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	ALT, n=111, 117, 120, 121, 112, 112, 112, 117	0.6 International Units/Liter (IU/L)	Standard Deviation 11.56
UMEC 15.6 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	CK, n=111, 118, 120, 121, 112, 112, 112, 117	6.3 International Units/Liter (IU/L)	Standard Deviation 70.2
UMEC 15.6 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	GGT, n=111, 118, 120, 121, 112, 112, 112, 117	0.7 International Units/Liter (IU/L)	Standard Deviation 9.63
UMEC 15.6 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	AST, n=110, 118, 120, 120, 112, 112, 112, 117	-0.3 International Units/Liter (IU/L)	Standard Deviation 6.26
UMEC 15.6 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	ALP, n=111, 118, 120, 121, 112, 112, 112, 117	-1.1 International Units/Liter (IU/L)	Standard Deviation 14.35
UMEC 31.25 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	ALT, n=111, 117, 120, 121, 112, 112, 112, 117	0.4 International Units/Liter (IU/L)	Standard Deviation 11.24
UMEC 31.25 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	GGT, n=111, 118, 120, 121, 112, 112, 112, 117	0.4 International Units/Liter (IU/L)	Standard Deviation 10.63
UMEC 31.25 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	ALP, n=111, 118, 120, 121, 112, 112, 112, 117	-1.8 International Units/Liter (IU/L)	Standard Deviation 13.55
UMEC 31.25 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	CK, n=111, 118, 120, 121, 112, 112, 112, 117	143.0 International Units/Liter (IU/L)	Standard Deviation 1486.66
UMEC 31.25 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	AST, n=110, 118, 120, 120, 112, 112, 112, 117	1.9 International Units/Liter (IU/L)	Standard Deviation 18.69
UMEC 62.5 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	AST, n=110, 118, 120, 120, 112, 112, 112, 117	-0.4 International Units/Liter (IU/L)	Standard Deviation 6.31
UMEC 62.5 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	GGT, n=111, 118, 120, 121, 112, 112, 112, 117	0.0 International Units/Liter (IU/L)	Standard Deviation 9.74
UMEC 62.5 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	ALP, n=111, 118, 120, 121, 112, 112, 112, 117	-2.0 International Units/Liter (IU/L)	Standard Deviation 10.73
UMEC 62.5 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	ALT, n=111, 117, 120, 121, 112, 112, 112, 117	-0.1 International Units/Liter (IU/L)	Standard Deviation 7.18
UMEC 62.5 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	CK, n=111, 118, 120, 121, 112, 112, 112, 117	-10.0 International Units/Liter (IU/L)	Standard Deviation 73.53
UMEC 125 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	AST, n=110, 118, 120, 120, 112, 112, 112, 117	-0.6 International Units/Liter (IU/L)	Standard Deviation 7.51
UMEC 125 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	ALP, n=111, 118, 120, 121, 112, 112, 112, 117	-2.8 International Units/Liter (IU/L)	Standard Deviation 14.16
UMEC 125 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	ALT, n=111, 117, 120, 121, 112, 112, 112, 117	-1.7 International Units/Liter (IU/L)	Standard Deviation 8.44
UMEC 125 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	CK, n=111, 118, 120, 121, 112, 112, 112, 117	-2.5 International Units/Liter (IU/L)	Standard Deviation 147.85
UMEC 125 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	GGT, n=111, 118, 120, 121, 112, 112, 112, 117	-0.6 International Units/Liter (IU/L)	Standard Deviation 8.31
UMEC 250 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	AST, n=110, 118, 120, 120, 112, 112, 112, 117	0.7 International Units/Liter (IU/L)	Standard Deviation 8.39
UMEC 250 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	CK, n=111, 118, 120, 121, 112, 112, 112, 117	7.7 International Units/Liter (IU/L)	Standard Deviation 105.96
UMEC 250 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	ALT, n=111, 117, 120, 121, 112, 112, 112, 117	1.4 International Units/Liter (IU/L)	Standard Deviation 9.8
UMEC 250 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	ALP, n=111, 118, 120, 121, 112, 112, 112, 117	-0.6 International Units/Liter (IU/L)	Standard Deviation 10.9
UMEC 250 µg QD	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	GGT, n=111, 118, 120, 121, 112, 112, 112, 117	0.2 International Units/Liter (IU/L)	Standard Deviation 12.15
UMEC 15.6 µg BID	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	AST, n=110, 118, 120, 120, 112, 112, 112, 117	0.6 International Units/Liter (IU/L)	Standard Deviation 7.24
UMEC 15.6 µg BID	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	ALP, n=111, 118, 120, 121, 112, 112, 112, 117	-0.6 International Units/Liter (IU/L)	Standard Deviation 14.05
UMEC 15.6 µg BID	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	ALT, n=111, 117, 120, 121, 112, 112, 112, 117	1.7 International Units/Liter (IU/L)	Standard Deviation 16.17
UMEC 15.6 µg BID	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	GGT, n=111, 118, 120, 121, 112, 112, 112, 117	2.0 International Units/Liter (IU/L)	Standard Deviation 10.18
UMEC 15.6 µg BID	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	CK, n=111, 118, 120, 121, 112, 112, 112, 117	6.9 International Units/Liter (IU/L)	Standard Deviation 100.44
UMEC 31.25 µg BID	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	GGT, n=111, 118, 120, 121, 112, 112, 112, 117	0.9 International Units/Liter (IU/L)	Standard Deviation 10.61
UMEC 31.25 µg BID	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	CK, n=111, 118, 120, 121, 112, 112, 112, 117	19.8 International Units/Liter (IU/L)	Standard Deviation 284.94
UMEC 31.25 µg BID	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	ALP, n=111, 118, 120, 121, 112, 112, 112, 117	-1.5 International Units/Liter (IU/L)	Standard Deviation 9.88
UMEC 31.25 µg BID	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	AST, n=110, 118, 120, 120, 112, 112, 112, 117	-0.3 International Units/Liter (IU/L)	Standard Deviation 9.59
UMEC 31.25 µg BID	Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period	ALT, n=111, 117, 120, 121, 112, 112, 112, 117	-1.3 International Units/Liter (IU/L)	Standard Deviation 8.73

Primary

Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period

Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils (ANC - Absolute neutrophil \[neut\] count), platelet, and leucocytes count at Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Time frame: Baseline and Day 14 of each treatment period (up to Study Day 70)

Arm	Measure	Group	Value (MEAN)	Dispersion
All Study Treatments	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Lymphocytes, n=109, 121, 124, 117,110,112,111,121	-0.038 10^9 cells/Liter (GI/L)	Standard Deviation 0.5767
All Study Treatments	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Eosinophils, n= 109, 121, 124, 117,110,112,111,121	0.097 10^9 cells/Liter (GI/L)	Standard Deviation 0.24
All Study Treatments	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Basophil, n=109, 121, 124, 117, 110, 112, 111, 121	0.003 10^9 cells/Liter (GI/L)	Standard Deviation 0.0212
All Study Treatments	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Monocytes, n=109, 121, 124, 117, 110, 112, 111,121	0.017 10^9 cells/Liter (GI/L)	Standard Deviation 0.1278
All Study Treatments	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Total Neut, n= 109, 121, 124, 117, 110,112,111,121	-0.204 10^9 cells/Liter (GI/L)	Standard Deviation 1.4615
All Study Treatments	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Segmented Neut, n=109,121,124,117,110,112,111,121	-0.204 10^9 cells/Liter (GI/L)	Standard Deviation 1.4615
All Study Treatments	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Platelets,n=109, 121, 124, 119, 110, 112, 111, 119	-1.4 10^9 cells/Liter (GI/L)	Standard Deviation 40.21
All Study Treatments	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Leukocytes,n=109,121,124, 117, 110, 112, 111, 121	-0.12 10^9 cells/Liter (GI/L)	Standard Deviation 1.74
UMEC 15.6 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Total Neut, n= 109, 121, 124, 117, 110,112,111,121	0.032 10^9 cells/Liter (GI/L)	Standard Deviation 1.2279
UMEC 15.6 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Lymphocytes, n=109, 121, 124, 117,110,112,111,121	-0.064 10^9 cells/Liter (GI/L)	Standard Deviation 0.5882
UMEC 15.6 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Segmented Neut, n=109,121,124,117,110,112,111,121	0.032 10^9 cells/Liter (GI/L)	Standard Deviation 1.2279
UMEC 15.6 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Platelets,n=109, 121, 124, 119, 110, 112, 111, 119	-0.7 10^9 cells/Liter (GI/L)	Standard Deviation 30.35
UMEC 15.6 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Basophil, n=109, 121, 124, 117, 110, 112, 111, 121	-0.001 10^9 cells/Liter (GI/L)	Standard Deviation 0.0173
UMEC 15.6 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Monocytes, n=109, 121, 124, 117, 110, 112, 111,121	0.029 10^9 cells/Liter (GI/L)	Standard Deviation 0.1366
UMEC 15.6 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Eosinophils, n= 109, 121, 124, 117,110,112,111,121	0.023 10^9 cells/Liter (GI/L)	Standard Deviation 0.1988
UMEC 15.6 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Leukocytes,n=109,121,124, 117, 110, 112, 111, 121	0.01 10^9 cells/Liter (GI/L)	Standard Deviation 1.385
UMEC 31.25 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Platelets,n=109, 121, 124, 119, 110, 112, 111, 119	-1.0 10^9 cells/Liter (GI/L)	Standard Deviation 36.65
UMEC 31.25 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Total Neut, n= 109, 121, 124, 117, 110,112,111,121	0.119 10^9 cells/Liter (GI/L)	Standard Deviation 1.871
UMEC 31.25 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Leukocytes,n=109,121,124, 117, 110, 112, 111, 121	0.10 10^9 cells/Liter (GI/L)	Standard Deviation 1.867
UMEC 31.25 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Lymphocytes, n=109, 121, 124, 117,110,112,111,121	-0.050 10^9 cells/Liter (GI/L)	Standard Deviation 0.585
UMEC 31.25 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Segmented Neut, n=109,121,124,117,110,112,111,121	0.119 10^9 cells/Liter (GI/L)	Standard Deviation 1.871
UMEC 31.25 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Monocytes, n=109, 121, 124, 117, 110, 112, 111,121	0.005 10^9 cells/Liter (GI/L)	Standard Deviation 0.1173
UMEC 31.25 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Basophil, n=109, 121, 124, 117, 110, 112, 111, 121	-0.000 10^9 cells/Liter (GI/L)	Standard Deviation 0.0184
UMEC 31.25 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Eosinophils, n= 109, 121, 124, 117,110,112,111,121	0.029 10^9 cells/Liter (GI/L)	Standard Deviation 0.1928
UMEC 62.5 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Leukocytes,n=109,121,124, 117, 110, 112, 111, 121	-0.15 10^9 cells/Liter (GI/L)	Standard Deviation 1.664
UMEC 62.5 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Eosinophils, n= 109, 121, 124, 117,110,112,111,121	0.036 10^9 cells/Liter (GI/L)	Standard Deviation 0.2056
UMEC 62.5 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Basophil, n=109, 121, 124, 117, 110, 112, 111, 121	0.001 10^9 cells/Liter (GI/L)	Standard Deviation 0.0178
UMEC 62.5 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Monocytes, n=109, 121, 124, 117, 110, 112, 111,121	0.017 10^9 cells/Liter (GI/L)	Standard Deviation 0.1185
UMEC 62.5 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Lymphocytes, n=109, 121, 124, 117,110,112,111,121	-0.033 10^9 cells/Liter (GI/L)	Standard Deviation 0.4986
UMEC 62.5 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Total Neut, n= 109, 121, 124, 117, 110,112,111,121	-0.175 10^9 cells/Liter (GI/L)	Standard Deviation 1.5228
UMEC 62.5 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Segmented Neut, n=109,121,124,117,110,112,111,121	-0.175 10^9 cells/Liter (GI/L)	Standard Deviation 1.5228
UMEC 62.5 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Platelets,n=109, 121, 124, 119, 110, 112, 111, 119	-2.3 10^9 cells/Liter (GI/L)	Standard Deviation 36.32
UMEC 125 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Monocytes, n=109, 121, 124, 117, 110, 112, 111,121	0.029 10^9 cells/Liter (GI/L)	Standard Deviation 0.1348
UMEC 125 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Platelets,n=109, 121, 124, 119, 110, 112, 111, 119	-2.1 10^9 cells/Liter (GI/L)	Standard Deviation 34.17
UMEC 125 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Lymphocytes, n=109, 121, 124, 117,110,112,111,121	-0.043 10^9 cells/Liter (GI/L)	Standard Deviation 0.5366
UMEC 125 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Basophil, n=109, 121, 124, 117, 110, 112, 111, 121	0.006 10^9 cells/Liter (GI/L)	Standard Deviation 0.023
UMEC 125 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Leukocytes,n=109,121,124, 117, 110, 112, 111, 121	-0.14 10^9 cells/Liter (GI/L)	Standard Deviation 1.4
UMEC 125 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Total Neut, n= 109, 121, 124, 117, 110,112,111,121	-0.161 10^9 cells/Liter (GI/L)	Standard Deviation 1.178
UMEC 125 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Segmented Neut, n=109,121,124,117,110,112,111,121	-0.161 10^9 cells/Liter (GI/L)	Standard Deviation 1.178
UMEC 125 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Eosinophils, n= 109, 121, 124, 117,110,112,111,121	0.036 10^9 cells/Liter (GI/L)	Standard Deviation 0.1944
UMEC 250 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Leukocytes,n=109,121,124, 117, 110, 112, 111, 121	0.02 10^9 cells/Liter (GI/L)	Standard Deviation 1.913
UMEC 250 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Eosinophils, n= 109, 121, 124, 117,110,112,111,121	0.039 10^9 cells/Liter (GI/L)	Standard Deviation 0.2583
UMEC 250 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Lymphocytes, n=109, 121, 124, 117,110,112,111,121	-0.152 10^9 cells/Liter (GI/L)	Standard Deviation 0.5203
UMEC 250 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Basophil, n=109, 121, 124, 117, 110, 112, 111, 121	-0.001 10^9 cells/Liter (GI/L)	Standard Deviation 0.0162
UMEC 250 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Platelets,n=109, 121, 124, 119, 110, 112, 111, 119	-8.4 10^9 cells/Liter (GI/L)	Standard Deviation 40.89
UMEC 250 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Segmented Neut, n=109,121,124,117,110,112,111,121	0.107 10^9 cells/Liter (GI/L)	Standard Deviation 1.8329
UMEC 250 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Total Neut, n= 109, 121, 124, 117, 110,112,111,121	0.107 10^9 cells/Liter (GI/L)	Standard Deviation 1.8329
UMEC 250 µg QD	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Monocytes, n=109, 121, 124, 117, 110, 112, 111,121	0.030 10^9 cells/Liter (GI/L)	Standard Deviation 0.1289
UMEC 15.6 µg BID	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Lymphocytes, n=109, 121, 124, 117,110,112,111,121	-0.156 10^9 cells/Liter (GI/L)	Standard Deviation 0.5552
UMEC 15.6 µg BID	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Eosinophils, n= 109, 121, 124, 117,110,112,111,121	0.040 10^9 cells/Liter (GI/L)	Standard Deviation 0.1799
UMEC 15.6 µg BID	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Monocytes, n=109, 121, 124, 117, 110, 112, 111,121	0.010 10^9 cells/Liter (GI/L)	Standard Deviation 0.1168
UMEC 15.6 µg BID	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Total Neut, n= 109, 121, 124, 117, 110,112,111,121	-0.133 10^9 cells/Liter (GI/L)	Standard Deviation 1.2785
UMEC 15.6 µg BID	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Segmented Neut, n=109,121,124,117,110,112,111,121	-0.133 10^9 cells/Liter (GI/L)	Standard Deviation 1.2785
UMEC 15.6 µg BID	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Leukocytes,n=109,121,124, 117, 110, 112, 111, 121	-0.24 10^9 cells/Liter (GI/L)	Standard Deviation 1.423
UMEC 15.6 µg BID	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Platelets,n=109, 121, 124, 119, 110, 112, 111, 119	-2.2 10^9 cells/Liter (GI/L)	Standard Deviation 33.07
UMEC 15.6 µg BID	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Basophil, n=109, 121, 124, 117, 110, 112, 111, 121	-0.002 10^9 cells/Liter (GI/L)	Standard Deviation 0.0161
UMEC 31.25 µg BID	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Leukocytes,n=109,121,124, 117, 110, 112, 111, 121	-0.11 10^9 cells/Liter (GI/L)	Standard Deviation 1.402
UMEC 31.25 µg BID	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Segmented Neut, n=109,121,124,117,110,112,111,121	-0.080 10^9 cells/Liter (GI/L)	Standard Deviation 1.1597
UMEC 31.25 µg BID	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Total Neut, n= 109, 121, 124, 117, 110,112,111,121	-0.080 10^9 cells/Liter (GI/L)	Standard Deviation 1.1597
UMEC 31.25 µg BID	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Monocytes, n=109, 121, 124, 117, 110, 112, 111,121	-0.000 10^9 cells/Liter (GI/L)	Standard Deviation 0.106
UMEC 31.25 µg BID	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Lymphocytes, n=109, 121, 124, 117,110,112,111,121	-0.069 10^9 cells/Liter (GI/L)	Standard Deviation 0.6148
UMEC 31.25 µg BID	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Eosinophils, n= 109, 121, 124, 117,110,112,111,121	0.039 10^9 cells/Liter (GI/L)	Standard Deviation 0.1862
UMEC 31.25 µg BID	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Basophil, n=109, 121, 124, 117, 110, 112, 111, 121	0.000 10^9 cells/Liter (GI/L)	Standard Deviation 0.0184
UMEC 31.25 µg BID	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period	Platelets,n=109, 121, 124, 119, 110, 112, 111, 119	-1.0 10^9 cells/Liter (GI/L)	Standard Deviation 39.34

Primary

Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period

Blood samples were collected for the measurement of chloride, caron dioxide, glucose, potassium, sodium, and urea/BUN at Baseline and Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Time frame: Baseline and Day 14 of each treatment period (up to Study Day 70)

Arm	Measure	Group	Value (MEAN)	Dispersion
All Study Treatments	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Urea/BUN, n=111, 118, 120, 121, 112, 112, 112, 117	0.11 Micromoles/Liter (µM/L)	Standard Deviation 1.382
All Study Treatments	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Chloride, n=111, 118, 120, 121, 112, 112, 112, 117	0.1 Micromoles/Liter (µM/L)	Standard Deviation 2.11
All Study Treatments	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Carbon dioxide, n=110,118,120,120,112,112,112,117	-0.6 Micromoles/Liter (µM/L)	Standard Deviation 2.16
All Study Treatments	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Glucose, n=111, 118, 120, 121, 112, 112, 112, 117	0.01 Micromoles/Liter (µM/L)	Standard Deviation 1.134
All Study Treatments	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Sodium, n=111, 118, 120, 121, 112, 112, 112, 117	-0.2 Micromoles/Liter (µM/L)	Standard Deviation 1.78
All Study Treatments	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Potassium, n=110, 118, 120, 120, 112, 112, 112,117	0.02 Micromoles/Liter (µM/L)	Standard Deviation 0.4
UMEC 15.6 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Glucose, n=111, 118, 120, 121, 112, 112, 112, 117	0.04 Micromoles/Liter (µM/L)	Standard Deviation 0.975
UMEC 15.6 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Chloride, n=111, 118, 120, 121, 112, 112, 112, 117	0.4 Micromoles/Liter (µM/L)	Standard Deviation 2.29
UMEC 15.6 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Potassium, n=110, 118, 120, 120, 112, 112, 112,117	0.05 Micromoles/Liter (µM/L)	Standard Deviation 0.338
UMEC 15.6 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Urea/BUN, n=111, 118, 120, 121, 112, 112, 112, 117	0.34 Micromoles/Liter (µM/L)	Standard Deviation 1.149
UMEC 15.6 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Carbon dioxide, n=110,118,120,120,112,112,112,117	-0.4 Micromoles/Liter (µM/L)	Standard Deviation 2.73
UMEC 15.6 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Sodium, n=111, 118, 120, 121, 112, 112, 112, 117	0.2 Micromoles/Liter (µM/L)	Standard Deviation 2.06
UMEC 31.25 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Sodium, n=111, 118, 120, 121, 112, 112, 112, 117	-0.0 Micromoles/Liter (µM/L)	Standard Deviation 2.14
UMEC 31.25 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Glucose, n=111, 118, 120, 121, 112, 112, 112, 117	-0.15 Micromoles/Liter (µM/L)	Standard Deviation 0.95
UMEC 31.25 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Carbon dioxide, n=110,118,120,120,112,112,112,117	-0.6 Micromoles/Liter (µM/L)	Standard Deviation 2.54
UMEC 31.25 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Potassium, n=110, 118, 120, 120, 112, 112, 112,117	0.05 Micromoles/Liter (µM/L)	Standard Deviation 0.416
UMEC 31.25 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Urea/BUN, n=111, 118, 120, 121, 112, 112, 112, 117	0.02 Micromoles/Liter (µM/L)	Standard Deviation 1.197
UMEC 31.25 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Chloride, n=111, 118, 120, 121, 112, 112, 112, 117	0.4 Micromoles/Liter (µM/L)	Standard Deviation 2.29
UMEC 62.5 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Sodium, n=111, 118, 120, 121, 112, 112, 112, 117	-0.2 Micromoles/Liter (µM/L)	Standard Deviation 2.33
UMEC 62.5 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Chloride, n=111, 118, 120, 121, 112, 112, 112, 117	0.3 Micromoles/Liter (µM/L)	Standard Deviation 2.21
UMEC 62.5 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Carbon dioxide, n=110,118,120,120,112,112,112,117	-0.2 Micromoles/Liter (µM/L)	Standard Deviation 2.88
UMEC 62.5 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Glucose, n=111, 118, 120, 121, 112, 112, 112, 117	0.01 Micromoles/Liter (µM/L)	Standard Deviation 1.012
UMEC 62.5 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Potassium, n=110, 118, 120, 120, 112, 112, 112,117	0.03 Micromoles/Liter (µM/L)	Standard Deviation 0.42
UMEC 62.5 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Urea/BUN, n=111, 118, 120, 121, 112, 112, 112, 117	0.11 Micromoles/Liter (µM/L)	Standard Deviation 1.283
UMEC 125 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Sodium, n=111, 118, 120, 121, 112, 112, 112, 117	-0.1 Micromoles/Liter (µM/L)	Standard Deviation 1.99
UMEC 125 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Carbon dioxide, n=110,118,120,120,112,112,112,117	-0.4 Micromoles/Liter (µM/L)	Standard Deviation 2.11
UMEC 125 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Urea/BUN, n=111, 118, 120, 121, 112, 112, 112, 117	-0.04 Micromoles/Liter (µM/L)	Standard Deviation 1.322
UMEC 125 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Chloride, n=111, 118, 120, 121, 112, 112, 112, 117	0.6 Micromoles/Liter (µM/L)	Standard Deviation 2.18
UMEC 125 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Potassium, n=110, 118, 120, 120, 112, 112, 112,117	0.05 Micromoles/Liter (µM/L)	Standard Deviation 0.353
UMEC 125 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Glucose, n=111, 118, 120, 121, 112, 112, 112, 117	-0.29 Micromoles/Liter (µM/L)	Standard Deviation 0.848
UMEC 250 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Glucose, n=111, 118, 120, 121, 112, 112, 112, 117	-0.08 Micromoles/Liter (µM/L)	Standard Deviation 1.048
UMEC 250 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Potassium, n=110, 118, 120, 120, 112, 112, 112,117	0.02 Micromoles/Liter (µM/L)	Standard Deviation 0.412
UMEC 250 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Carbon dioxide, n=110,118,120,120,112,112,112,117	-0.0 Micromoles/Liter (µM/L)	Standard Deviation 2.55
UMEC 250 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Sodium, n=111, 118, 120, 121, 112, 112, 112, 117	-0.3 Micromoles/Liter (µM/L)	Standard Deviation 1.88
UMEC 250 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Chloride, n=111, 118, 120, 121, 112, 112, 112, 117	0.3 Micromoles/Liter (µM/L)	Standard Deviation 1.84
UMEC 250 µg QD	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Urea/BUN, n=111, 118, 120, 121, 112, 112, 112, 117	0.20 Micromoles/Liter (µM/L)	Standard Deviation 1.303
UMEC 15.6 µg BID	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Potassium, n=110, 118, 120, 120, 112, 112, 112,117	0.08 Micromoles/Liter (µM/L)	Standard Deviation 0.387
UMEC 15.6 µg BID	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Sodium, n=111, 118, 120, 121, 112, 112, 112, 117	-0.2 Micromoles/Liter (µM/L)	Standard Deviation 2.23
UMEC 15.6 µg BID	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Chloride, n=111, 118, 120, 121, 112, 112, 112, 117	0.3 Micromoles/Liter (µM/L)	Standard Deviation 2.22
UMEC 15.6 µg BID	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Glucose, n=111, 118, 120, 121, 112, 112, 112, 117	-0.09 Micromoles/Liter (µM/L)	Standard Deviation 1.022
UMEC 15.6 µg BID	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Urea/BUN, n=111, 118, 120, 121, 112, 112, 112, 117	0.02 Micromoles/Liter (µM/L)	Standard Deviation 1.184
UMEC 15.6 µg BID	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Carbon dioxide, n=110,118,120,120,112,112,112,117	-0.5 Micromoles/Liter (µM/L)	Standard Deviation 2.69
UMEC 31.25 µg BID	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Potassium, n=110, 118, 120, 120, 112, 112, 112,117	0.09 Micromoles/Liter (µM/L)	Standard Deviation 0.398
UMEC 31.25 µg BID	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Glucose, n=111, 118, 120, 121, 112, 112, 112, 117	-0.14 Micromoles/Liter (µM/L)	Standard Deviation 0.778
UMEC 31.25 µg BID	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Urea/BUN, n=111, 118, 120, 121, 112, 112, 112, 117	0.13 Micromoles/Liter (µM/L)	Standard Deviation 1.265
UMEC 31.25 µg BID	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Sodium, n=111, 118, 120, 121, 112, 112, 112, 117	-0.4 Micromoles/Liter (µM/L)	Standard Deviation 1.82
UMEC 31.25 µg BID	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Chloride, n=111, 118, 120, 121, 112, 112, 112, 117	0.3 Micromoles/Liter (µM/L)	Standard Deviation 2
UMEC 31.25 µg BID	Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period	Carbon dioxide, n=110,118,120,120,112,112,112,117	-0.6 Micromoles/Liter (µM/L)	Standard Deviation 2.38

Primary

Change From Baseline in Diastolic Blood Pressure on Day 14 of Each Treatment Period

Blood pressure measurement included diastolic blood pressure (DBP). Blood pressure was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Analysis was performed using a mixed model, including treatment, period, period Baseline and mean Baseline for the measure as fixed effects and participant as a random effect. Baseline is the value recorded pre-dose on Day 1 of each treatment period; mean Baseline is the mean of the Baselines for each participant and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Change from Baseline was calculated as the assessment value at Day 14 minus the Baseline value.

Time frame: Baseline and Day 14 of each treatment period (up to Study Day 70)

Population: ITT Population. Only those participants with data available at the specified time points were analyzed.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
All Study Treatments	Change From Baseline in Diastolic Blood Pressure on Day 14 of Each Treatment Period	-2.1 Millimeters of mercury (mmHg)	Standard Error 0.57
UMEC 15.6 µg QD	Change From Baseline in Diastolic Blood Pressure on Day 14 of Each Treatment Period	-0.5 Millimeters of mercury (mmHg)	Standard Error 0.55
UMEC 31.25 µg QD	Change From Baseline in Diastolic Blood Pressure on Day 14 of Each Treatment Period	-0.8 Millimeters of mercury (mmHg)	Standard Error 0.53
UMEC 62.5 µg QD	Change From Baseline in Diastolic Blood Pressure on Day 14 of Each Treatment Period	-0.2 Millimeters of mercury (mmHg)	Standard Error 0.54
UMEC 125 µg QD	Change From Baseline in Diastolic Blood Pressure on Day 14 of Each Treatment Period	0.3 Millimeters of mercury (mmHg)	Standard Error 0.57
UMEC 250 µg QD	Change From Baseline in Diastolic Blood Pressure on Day 14 of Each Treatment Period	0.0 Millimeters of mercury (mmHg)	Standard Error 0.55
UMEC 15.6 µg BID	Change From Baseline in Diastolic Blood Pressure on Day 14 of Each Treatment Period	0.6 Millimeters of mercury (mmHg)	Standard Error 0.56
UMEC 31.25 µg BID	Change From Baseline in Diastolic Blood Pressure on Day 14 of Each Treatment Period	-0.7 Millimeters of mercury (mmHg)	Standard Error 0.55

p-value: 0.0395% CI: [0.2, 3.2]Mixed Models Analysis

p-value: 0.07795% CI: [-0.1, 2.8]Mixed Models Analysis

p-value: 0.0195% CI: [0.5, 3.5]Mixed Models Analysis

p-value: 0.00295% CI: [0.9, 3.9]Mixed Models Analysis

p-value: 0.00595% CI: [0.7, 3.7]Mixed Models Analysis

p-value: <0.00195% CI: [1.2, 4.3]Mixed Models Analysis

p-value: 0.05495% CI: [0, 3]Mixed Models Analysis

Primary

Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period

Blood samples were collected for the measurement of direct bilirubin, indirect (ind) bilirubin, total bilirubin, and creatinine at Baseline and Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Time frame: Baseline and Day 14 of each treatment period (up to Study Day 70)

Arm	Measure	Group	Value (MEAN)	Dispersion
All Study Treatments	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Bilirubin, n=111,118,120,121,112,112,112,117	-1.0 Micromoles/Liter (µM/L)	Standard Deviation 3.94
All Study Treatments	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Direct bilirubin,n=111,118,120,121,112,112,112,117	-0.2 Micromoles/Liter (µM/L)	Standard Deviation 1.1
All Study Treatments	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Ind Bilirubin, n=111,118,120,121,112,112,112,117	-0.8 Micromoles/Liter (µM/L)	Standard Deviation 3.42
All Study Treatments	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Creatinine, n=111,118,120,121,112,112,112,117	0.27 Micromoles/Liter (µM/L)	Standard Deviation 9.218
UMEC 15.6 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Bilirubin, n=111,118,120,121,112,112,112,117	-0.9 Micromoles/Liter (µM/L)	Standard Deviation 3.69
UMEC 15.6 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Direct bilirubin,n=111,118,120,121,112,112,112,117	-0.1 Micromoles/Liter (µM/L)	Standard Deviation 1.1
UMEC 15.6 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Creatinine, n=111,118,120,121,112,112,112,117	-0.67 Micromoles/Liter (µM/L)	Standard Deviation 8.037
UMEC 15.6 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Ind Bilirubin, n=111,118,120,121,112,112,112,117	-0.8 Micromoles/Liter (µM/L)	Standard Deviation 3.03
UMEC 31.25 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Direct bilirubin,n=111,118,120,121,112,112,112,117	-0.1 Micromoles/Liter (µM/L)	Standard Deviation 0.99
UMEC 31.25 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Bilirubin, n=111,118,120,121,112,112,112,117	-0.7 Micromoles/Liter (µM/L)	Standard Deviation 3.36
UMEC 31.25 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Ind Bilirubin, n=111,118,120,121,112,112,112,117	-0.6 Micromoles/Liter (µM/L)	Standard Deviation 2.93
UMEC 31.25 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Creatinine, n=111,118,120,121,112,112,112,117	-0.76 Micromoles/Liter (µM/L)	Standard Deviation 6.242
UMEC 62.5 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Ind Bilirubin, n=111,118,120,121,112,112,112,117	-0.8 Micromoles/Liter (µM/L)	Standard Deviation 3.37
UMEC 62.5 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Bilirubin, n=111,118,120,121,112,112,112,117	-0.9 Micromoles/Liter (µM/L)	Standard Deviation 3.85
UMEC 62.5 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Creatinine, n=111,118,120,121,112,112,112,117	0.94 Micromoles/Liter (µM/L)	Standard Deviation 6.811
UMEC 62.5 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Direct bilirubin,n=111,118,120,121,112,112,112,117	-0.1 Micromoles/Liter (µM/L)	Standard Deviation 0.95
UMEC 125 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Bilirubin, n=111,118,120,121,112,112,112,117	-1.1 Micromoles/Liter (µM/L)	Standard Deviation 5.15
UMEC 125 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Direct bilirubin,n=111,118,120,121,112,112,112,117	-0.1 Micromoles/Liter (µM/L)	Standard Deviation 1.15
UMEC 125 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Ind Bilirubin, n=111,118,120,121,112,112,112,117	-1.1 Micromoles/Liter (µM/L)	Standard Deviation 4.42
UMEC 125 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Creatinine, n=111,118,120,121,112,112,112,117	-0.24 Micromoles/Liter (µM/L)	Standard Deviation 7.45
UMEC 250 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Bilirubin, n=111,118,120,121,112,112,112,117	-0.9 Micromoles/Liter (µM/L)	Standard Deviation 4.17
UMEC 250 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Direct bilirubin,n=111,118,120,121,112,112,112,117	-0.1 Micromoles/Liter (µM/L)	Standard Deviation 1.15
UMEC 250 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Ind Bilirubin, n=111,118,120,121,112,112,112,117	-0.8 Micromoles/Liter (µM/L)	Standard Deviation 3.6
UMEC 250 µg QD	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Creatinine, n=111,118,120,121,112,112,112,117	0.15 Micromoles/Liter (µM/L)	Standard Deviation 6.826
UMEC 15.6 µg BID	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Creatinine, n=111,118,120,121,112,112,112,117	0.30 Micromoles/Liter (µM/L)	Standard Deviation 7.297
UMEC 15.6 µg BID	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Ind Bilirubin, n=111,118,120,121,112,112,112,117	-0.7 Micromoles/Liter (µM/L)	Standard Deviation 3.63
UMEC 15.6 µg BID	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Bilirubin, n=111,118,120,121,112,112,112,117	-0.8 Micromoles/Liter (µM/L)	Standard Deviation 4.19
UMEC 15.6 µg BID	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Direct bilirubin,n=111,118,120,121,112,112,112,117	-0.1 Micromoles/Liter (µM/L)	Standard Deviation 1.08
UMEC 31.25 µg BID	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Creatinine, n=111,118,120,121,112,112,112,117	0.22 Micromoles/Liter (µM/L)	Standard Deviation 7.671
UMEC 31.25 µg BID	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Ind Bilirubin, n=111,118,120,121,112,112,112,117	-0.8 Micromoles/Liter (µM/L)	Standard Deviation 3.16
UMEC 31.25 µg BID	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Bilirubin, n=111,118,120,121,112,112,112,117	-0.9 Micromoles/Liter (µM/L)	Standard Deviation 3.68
UMEC 31.25 µg BID	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period	Direct bilirubin,n=111,118,120,121,112,112,112,117	-0.1 Micromoles/Liter (µM/L)	Standard Deviation 1.1

Primary

Change From Baseline in Hematocrit on Day 14 of Each Treatment Period

Blood samples were collected for the measurement of hematocrit (proportion of red blood cells in blood) at Baseline and Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Time frame: Baseline and Day 14 of each treatment period (up to Study Day 70)

Population: ITT Population. Only those participants with data available at the specified time points were analyzed.

Arm	Measure	Value (MEAN)	Dispersion
All Study Treatments	Change From Baseline in Hematocrit on Day 14 of Each Treatment Period	-0.0093 Proportion of red blood cells in blood	Standard Deviation 0.02298
UMEC 15.6 µg QD	Change From Baseline in Hematocrit on Day 14 of Each Treatment Period	-0.0118 Proportion of red blood cells in blood	Standard Deviation 0.0218
UMEC 31.25 µg QD	Change From Baseline in Hematocrit on Day 14 of Each Treatment Period	-0.0075 Proportion of red blood cells in blood	Standard Deviation 0.02271
UMEC 62.5 µg QD	Change From Baseline in Hematocrit on Day 14 of Each Treatment Period	-0.0092 Proportion of red blood cells in blood	Standard Deviation 0.02198
UMEC 125 µg QD	Change From Baseline in Hematocrit on Day 14 of Each Treatment Period	-0.0082 Proportion of red blood cells in blood	Standard Deviation 0.02452
UMEC 250 µg QD	Change From Baseline in Hematocrit on Day 14 of Each Treatment Period	-0.0079 Proportion of red blood cells in blood	Standard Deviation 0.02053
UMEC 15.6 µg BID	Change From Baseline in Hematocrit on Day 14 of Each Treatment Period	-0.0084 Proportion of red blood cells in blood	Standard Deviation 0.02259
UMEC 31.25 µg BID	Change From Baseline in Hematocrit on Day 14 of Each Treatment Period	-0.0087 Proportion of red blood cells in blood	Standard Deviation 0.02279

Primary

Change From Baseline in Pulse Rate on Day 14 of Each Treatment Period

Pulse rate was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Analysis was performed using a mixed model, including treatment, period, period Baseline and mean Baseline for the measure as fixed effects and participant as a random effect. Baseline is the value recorded pre-dose on Day 1 of each treatment period; mean Baseline is the mean of the Baselines for each participant and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Change from Baseline was calculated as the assessment value at Day 14 minus the Baseline value.

Time frame: Baseline and Day 14 of each treatment period (up to Study Day 70)

Population: ITT Population. Only those participants with data available at the specified time points were analyzed.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
All Study Treatments	Change From Baseline in Pulse Rate on Day 14 of Each Treatment Period	-0.4 Beats per minute	Standard Error 0.64
UMEC 15.6 µg QD	Change From Baseline in Pulse Rate on Day 14 of Each Treatment Period	-0.1 Beats per minute	Standard Error 0.62
UMEC 31.25 µg QD	Change From Baseline in Pulse Rate on Day 14 of Each Treatment Period	1.2 Beats per minute	Standard Error 0.6
UMEC 62.5 µg QD	Change From Baseline in Pulse Rate on Day 14 of Each Treatment Period	0.2 Beats per minute	Standard Error 0.61
UMEC 125 µg QD	Change From Baseline in Pulse Rate on Day 14 of Each Treatment Period	0.2 Beats per minute	Standard Error 0.64
UMEC 250 µg QD	Change From Baseline in Pulse Rate on Day 14 of Each Treatment Period	1.1 Beats per minute	Standard Error 0.62
UMEC 15.6 µg BID	Change From Baseline in Pulse Rate on Day 14 of Each Treatment Period	-0.4 Beats per minute	Standard Error 0.64
UMEC 31.25 µg BID	Change From Baseline in Pulse Rate on Day 14 of Each Treatment Period	-1.1 Beats per minute	Standard Error 0.62

p-value: 0.75295% CI: [-1.4, 2]Mixed Models Analysis

p-value: 0.07295% CI: [-0.1, 3.2]Mixed Models Analysis

p-value: 0.50395% CI: [-1.1, 2.2]Mixed Models Analysis

p-value: 0.47695% CI: [-1.1, 2.3]Mixed Models Analysis

p-value: 0.08495% CI: [-0.2, 3.2]Mixed Models Analysis

p-value: 0.9795% CI: [-1.8, 1.7]Mixed Models Analysis

p-value: 0.42395% CI: [-2.4, 1]Mixed Models Analysis

Primary

Change From Baseline in Systolic Blood Pressure on Day 14 of Each Treatment Period

Blood pressure measurement included systolic blood pressure (SBP). Blood pressure was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Analysis was performed using a mixed model, including treatment, period, period Baseline and mean Baseline for the measure as fixed effects and participant as a random effect. Baseline is the value recorded pre-dose on Day 1 of each treatment period; mean Baseline is the mean of the Baselines for each participant and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Change from Baseline was calculated as the assessment value at Day 14 minus the Baseline value.

Time frame: Baseline and Day 14 of each treatment period (up to Study Day 70)

Population: ITT Population. Only those participants with data available at the specified time points were analyzed.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
All Study Treatments	Change From Baseline in Systolic Blood Pressure on Day 14 of Each Treatment Period	-0.4 Millimeters of mercury (mmHg)	Standard Error 0.71
UMEC 15.6 µg QD	Change From Baseline in Systolic Blood Pressure on Day 14 of Each Treatment Period	-0.6 Millimeters of mercury (mmHg)	Standard Error 0.68
UMEC 31.25 µg QD	Change From Baseline in Systolic Blood Pressure on Day 14 of Each Treatment Period	-1.0 Millimeters of mercury (mmHg)	Standard Error 0.67
UMEC 62.5 µg QD	Change From Baseline in Systolic Blood Pressure on Day 14 of Each Treatment Period	1.1 Millimeters of mercury (mmHg)	Standard Error 0.68
UMEC 125 µg QD	Change From Baseline in Systolic Blood Pressure on Day 14 of Each Treatment Period	-0.6 Millimeters of mercury (mmHg)	Standard Error 0.71
UMEC 250 µg QD	Change From Baseline in Systolic Blood Pressure on Day 14 of Each Treatment Period	0.0 Millimeters of mercury (mmHg)	Standard Error 0.69
UMEC 15.6 µg BID	Change From Baseline in Systolic Blood Pressure on Day 14 of Each Treatment Period	0.3 Millimeters of mercury (mmHg)	Standard Error 0.71
UMEC 31.25 µg BID	Change From Baseline in Systolic Blood Pressure on Day 14 of Each Treatment Period	-1.2 Millimeters of mercury (mmHg)	Standard Error 0.69

p-value: 0.8495% CI: [-2.1, 1.7]Mixed Models Analysis

p-value: 0.55395% CI: [-2.4, 1.3]Mixed Models Analysis

p-value: 0.12195% CI: [-0.4, 3.3]Mixed Models Analysis

p-value: 0.81495% CI: [-2.1, 1.7]Mixed Models Analysis

p-value: 0.68395% CI: [-1.5, 2.3]Mixed Models Analysis

p-value: 0.45695% CI: [-1.2, 2.7]Mixed Models Analysis

p-value: 0.39995% CI: [-2.7, 1.1]Mixed Models Analysis

Primary

Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period

Blood samples were collected for the measurement of the percentage of basophils, eosinophils, lymphocytes, monocytes, and segmented neutrophils (neut) at Baseline and Day 14. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Time frame: Baseline and Day 14 of each treatment period (up to Study Day 70)

Arm	Measure	Group	Value (MEAN)	Dispersion
All Study Treatments	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Segmented Neut, n=109,121,124,117,110,112,111,121	-1.80 Percentage of cells in blood	Standard Deviation 8.264
All Study Treatments	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Basophils, n=109,121,124,117,111,112,111,121	0.05 Percentage of cells in blood	Standard Deviation 0.302
All Study Treatments	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Eosinophils, n= 109,121,124,117,110,112,111,121	1.45 Percentage of cells in blood	Standard Deviation 3.38
All Study Treatments	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Lymphocytes, n=109,121,124,117,110,112,111,121	-0.00 Percentage of cells in blood	Standard Deviation 6.861
All Study Treatments	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Neutrophils, n=109,121,124,117,110,112,111,121	-1.80 Percentage of cells in blood	Standard Deviation 8.264
All Study Treatments	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Monocytes, n=109,121,124,117,110,112,111,121	0.30 Percentage of cells in blood	Standard Deviation 1.735
UMEC 15.6 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Lymphocytes, n=109,121,124,117,110,112,111,121	-0.64 Percentage of cells in blood	Standard Deviation 7.59
UMEC 15.6 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Basophils, n=109,121,124,117,111,112,111,121	-0.01 Percentage of cells in blood	Standard Deviation 0.24
UMEC 15.6 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Monocytes, n=109,121,124,117,110,112,111,121	0.45 Percentage of cells in blood	Standard Deviation 1.941
UMEC 15.6 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Segmented Neut, n=109,121,124,117,110,112,111,121	-0.11 Percentage of cells in blood	Standard Deviation 8.872
UMEC 15.6 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Eosinophils, n= 109,121,124,117,110,112,111,121	0.30 Percentage of cells in blood	Standard Deviation 2.782
UMEC 15.6 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Neutrophils, n=109,121,124,117,110,112,111,121	-0.11 Percentage of cells in blood	Standard Deviation 8.872
UMEC 31.25 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Neutrophils, n=109,121,124,117,110,112,111,121	-0.04 Percentage of cells in blood	Standard Deviation 8.739
UMEC 31.25 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Lymphocytes, n=109,121,124,117,110,112,111,121	-0.29 Percentage of cells in blood	Standard Deviation 7.485
UMEC 31.25 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Eosinophils, n= 109,121,124,117,110,112,111,121	0.32 Percentage of cells in blood	Standard Deviation 2.896
UMEC 31.25 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Monocytes, n=109,121,124,117,110,112,111,121	0.04 Percentage of cells in blood	Standard Deviation 1.798
UMEC 31.25 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Segmented Neut, n=109,121,124,117,110,112,111,121	-0.04 Percentage of cells in blood	Standard Deviation 8.739
UMEC 31.25 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Basophils, n=109,121,124,117,111,112,111,121	-0.02 Percentage of cells in blood	Standard Deviation 0.273
UMEC 62.5 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Neutrophils, n=109,121,124,117,110,112,111,121	-1.73 Percentage of cells in blood	Standard Deviation 9.048
UMEC 62.5 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Basophils, n=109,121,124,117,111,112,111,121	0.03 Percentage of cells in blood	Standard Deviation 0.286
UMEC 62.5 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Eosinophils, n= 109,121,124,117,110,112,111,121	0.68 Percentage of cells in blood	Standard Deviation 3.1
UMEC 62.5 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Lymphocytes, n=109,121,124,117,110,112,111,121	0.62 Percentage of cells in blood	Standard Deviation 8.069
UMEC 62.5 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Monocytes, n=109,121,124,117,110,112,111,121	0.41 Percentage of cells in blood	Standard Deviation 1.787
UMEC 62.5 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Segmented Neut, n=109,121,124,117,110,112,111,121	-1.73 Percentage of cells in blood	Standard Deviation 9.048
UMEC 125 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Neutrophils, n=109,121,124,117,110,112,111,121	-1.11 Percentage of cells in blood	Standard Deviation 8.107
UMEC 125 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Eosinophils, n= 109,121,124,117,110,112,111,121	0.56 Percentage of cells in blood	Standard Deviation 2.403
UMEC 125 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Segmented Neut, n=109,121,124,117,110,112,111,121	-1.11 Percentage of cells in blood	Standard Deviation 8.107
UMEC 125 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Basophils, n=109,121,124,117,111,112,111,121	0.08 Percentage of cells in blood	Standard Deviation 0.318
UMEC 125 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Monocytes, n=109,121,124,117,110,112,111,121	0.52 Percentage of cells in blood	Standard Deviation 1.719
UMEC 125 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Lymphocytes, n=109,121,124,117,110,112,111,121	-0.06 Percentage of cells in blood	Standard Deviation 6.996
UMEC 250 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Lymphocytes, n=109,121,124,117,110,112,111,121	-1.97 Percentage of cells in blood	Standard Deviation 8.203
UMEC 250 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Monocytes, n=109,121,124,117,110,112,111,121	0.45 Percentage of cells in blood	Standard Deviation 1.622
UMEC 250 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Eosinophils, n= 109,121,124,117,110,112,111,121	0.55 Percentage of cells in blood	Standard Deviation 3.142
UMEC 250 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Neutrophils, n=109,121,124,117,110,112,111,121	0.96 Percentage of cells in blood	Standard Deviation 9.319
UMEC 250 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Basophils, n=109,121,124,117,111,112,111,121	0.00 Percentage of cells in blood	Standard Deviation 0.212
UMEC 250 µg QD	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Segmented Neut, n=109,121,124,117,110,112,111,121	0.96 Percentage of cells in blood	Standard Deviation 9.319
UMEC 15.6 µg BID	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Monocytes, n=109,121,124,117,110,112,111,121	0.43 Percentage of cells in blood	Standard Deviation 2.626
UMEC 15.6 µg BID	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Neutrophils, n=109,121,124,117,110,112,111,121	-0.30 Percentage of cells in blood	Standard Deviation 9.252
UMEC 15.6 µg BID	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Basophils, n=109,121,124,117,111,112,111,121	-0.02 Percentage of cells in blood	Standard Deviation 0.248
UMEC 15.6 µg BID	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Lymphocytes, n=109,121,124,117,110,112,111,121	-0.76 Percentage of cells in blood	Standard Deviation 8.001
UMEC 15.6 µg BID	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Segmented Neut, n=109,121,124,117,110,112,111,121	-0.30 Percentage of cells in blood	Standard Deviation 9.252
UMEC 15.6 µg BID	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Eosinophils, n= 109,121,124,117,110,112,111,121	0.65 Percentage of cells in blood	Standard Deviation 2.537
UMEC 31.25 µg BID	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Monocytes, n=109,121,124,117,110,112,111,121	0.07 Percentage of cells in blood	Standard Deviation 1.585
UMEC 31.25 µg BID	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Lymphocytes, n=109,121,124,117,110,112,111,121	-0.46 Percentage of cells in blood	Standard Deviation 7.65
UMEC 31.25 µg BID	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Segmented Neut, n=109,121,124,117,110,112,111,121	-0.17 Percentage of cells in blood	Standard Deviation 8.676
UMEC 31.25 µg BID	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Neutrophils, n=109,121,124,117,110,112,111,121	-0.17 Percentage of cells in blood	Standard Deviation 8.676
UMEC 31.25 µg BID	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Basophils, n=109,121,124,117,111,112,111,121	0.00 Percentage of cells in blood	Standard Deviation 0.268
UMEC 31.25 µg BID	Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period	Eosinophils, n= 109,121,124,117,110,112,111,121	0.56 Percentage of cells in blood	Standard Deviation 2.481

Primary

Change From Baseline in Trough FEV1 on Day 15 of Each Treatment Period

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on Treatment Day 15 is defined as the value obtained 24 hours after the morning dose administered on Day 14. Analysis was performed using a mixed model, including treatment, period, period Baseline FEV1 and mean Baseline FEV1 as fixed effects and participant as a random effect. Baseline is the FEV1 value recorded pre-dose on Day 1 of each treatment period; mean Baseline is the mean of the Baselines for each participant and period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Change from Baseline for each treatment period is the trough FEV1 at Day 15 minus the Baseline value for that treatment period.

Time frame: Day 15 of each treatment period (up to Study Day 71)

Population: ITT Population. All participants with \>=1 post-Baseline assessment and non-missing covariate data are included in the analysis. The number of participants represents participants who provided data at Day 15.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
All Study Treatments	Change From Baseline in Trough FEV1 on Day 15 of Each Treatment Period	0.046 Liters	Standard Error 0.0235
UMEC 15.6 µg QD	Change From Baseline in Trough FEV1 on Day 15 of Each Treatment Period	0.112 Liters	Standard Error 0.0226
UMEC 31.25 µg QD	Change From Baseline in Trough FEV1 on Day 15 of Each Treatment Period	0.076 Liters	Standard Error 0.0222
UMEC 62.5 µg QD	Change From Baseline in Trough FEV1 on Day 15 of Each Treatment Period	0.080 Liters	Standard Error 0.0224
UMEC 125 µg QD	Change From Baseline in Trough FEV1 on Day 15 of Each Treatment Period	0.134 Liters	Standard Error 0.0232
UMEC 250 µg QD	Change From Baseline in Trough FEV1 on Day 15 of Each Treatment Period	0.057 Liters	Standard Error 0.0228
UMEC 15.6 µg BID	Change From Baseline in Trough FEV1 on Day 15 of Each Treatment Period	0.103 Liters	Standard Error 0.0232
UMEC 31.25 µg BID	Change From Baseline in Trough FEV1 on Day 15 of Each Treatment Period	0.097 Liters	Standard Error 0.0227

p-value: 0.03695% CI: [0.004, 0.127]Mixed Models Analysis

p-value: 0.33195% CI: [-0.03, 0.09]Mixed Models Analysis

p-value: 0.27295% CI: [-0.027, 0.095]Mixed Models Analysis

p-value: 0.00595% CI: [0.026, 0.149]Mixed Models Analysis

p-value: 0.72295% CI: [-0.05, 0.073]Mixed Models Analysis

p-value: 0.07695% CI: [-0.006, 0.119]Mixed Models Analysis

p-value: 0.10195% CI: [-0.01, 0.113]Mixed Models Analysis

Primary

Final Dose-response Model for Trough Forced Expiratory Volume in One Second (FEV1)

Dose-response was conducted for both QD and BID UMEC doses on trough FEV1 (measure of lung function, defined as the maximal amount of air that can be forcefully exhaled in 1 second) on D 15. Total daily dose of UMEC was used in the modeling. The null model was the final model. The null model is defined as: CFEV1,ij=(THETA1+ETA1j)\*meanBL+(THETA2+ETA1j)\*periodBL+EPSij, where CFEV1,ij represents the change from BL in trough FEV1 for participant j measured at period i. THETA1 and THETA2 were the slopes with respect to meanBL and periodBL, respectively. Omegas were the variance of the slopes on meanBL and periodBL (ETA1j, ETA2j) for each participant and Sigma was the variance of the residual errors (EPSij). MeanBL is the mean of the Baseline (BL) which is the FEV1 value recorded pre-dose on D 1 of each TP; periodBL is the difference between the BL and the meanBL in each TP for each participant.

Time frame: Day 15 of each treatment period (up to Study Day 71)

Population: Intent-To-Treat (ITT) Population: : all participants randomized to treatment and who received at least one dose of study medication. All participants with \>=1 post-Baseline assessment and non-missing covariate data are included in the analysis. The number of participants represents participants who provided data at Day 15.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
All Study Treatments	Final Dose-response Model for Trough Forced Expiratory Volume in One Second (FEV1)	Omega (mean Baseline)	0.00371 unitless
All Study Treatments	Final Dose-response Model for Trough Forced Expiratory Volume in One Second (FEV1)	Theta1 (mean Baseline)	0.0363 unitless
All Study Treatments	Final Dose-response Model for Trough Forced Expiratory Volume in One Second (FEV1)	Theta2 (period Baseline)	-0.97 unitless
All Study Treatments	Final Dose-response Model for Trough Forced Expiratory Volume in One Second (FEV1)	Omega (period Baseline)	0.149 unitless
All Study Treatments	Final Dose-response Model for Trough Forced Expiratory Volume in One Second (FEV1)	Sigma (Variance of Residual error)	0.0393 unitless

Primary

Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period

Urinalysis parameters included: Urine Bilirubin (UB), Urine Occult Blood (UOB), Urine Glucose (UG), Urine Ketones (UK), Urine Nitrite (UN), Urine Protein (UP), and Urine Leukocyte Esterase test for detecting White Blood Cell (UWBC). The dipstick was a strip used to detect the presence or absence of these parameters in the urine sample. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative (Neg), Trace (T), 1+, 2+, and 3+, and for UG the result can be read as Neg, T, T or 1/10 G/dL, 1+ or 1/4 G/dL, 3+ or 1 G/dL, indicating proportional concentrations in the urine sample. Data are reported as the number of participants who had neg, T, 1+, 2+ and 3+ levels at Day 14.

Time frame: Baseline and Day 14 of each treatment period (up to Study Day 70))

Arm	Measure	Group	Value (NUMBER)
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 3+, n=109,121,125,120,112,113,112,119	5 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 1+, n=109,121,125,120,112,113,112,119	6 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, T, n=109,121,125,120,112,113,112,119	4 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UB, Neg, n=109,121,125,120,112, 113,112,119	109 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UN, Pos, n=109,121,125,120,112,113,112,119	12 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, T, n=109,121,125,120,112,113,112,119	8 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, T, n=109,121,125,120,112,113,112,119	0 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 3+, n=109,121,125,120,112,113,112,119	6 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, Neg, n=109,121,125,120,112,113,112,119	107 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 1+, n=109,121,125,120,112,113,112,119	1 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, Neg, n=109,121,125,120,112,113,112,119	103 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 2+, n=109,121,125,120,112,113,112,119	0 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 3+, n=109,121,125,120,112,113,112,119	1 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 2+, n=109,121,125,120,112,113,112,119	4 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, Neg, n=109,121,125,120,112,113,112,119	85 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, 1+ or 1/4, n=109,121,125,120,112,113,112,119	1 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, T, n=109,121,125,120,112,113,112,119	6 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 2+, n=109,121,125,120,112,113,112,119	5 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, T, n=109,121,125,120,112,113,112,119	4 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, 1+, n=109,121,125,120,112,113,112,119	4 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UN, Neg, n=109,121,125,120,112,113,112,119	97 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 1+, n=109,121,125,120,112,113,112,119	5 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, Neg, n=109,121,125,120,112,113,112,119	88 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, 3+ or 1, n=109,121,125,120,112,113,112,119	1 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, Neg, n=109,121,125,120,112,113,112,119	99 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, 2+, n=109,121,125,120,112,113,112,119	2 Participants
All Study Treatments	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, T or 1/10, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, T, n=109,121,125,120,112,113,112,119	6 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, 2+, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, Neg, n=109,121,125,120,112,113,112,119	118 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 3+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UB, Neg, n=109,121,125,120,112, 113,112,119	121 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, T or 1/10, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, 1+, n=109,121,125,120,112,113,112,119	2 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, Neg, n=109,121,125,120,112,113,112,119	101 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, T, n=109,121,125,120,112,113,112,119	8 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 2+, n=109,121,125,120,112,113,112,119	8 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, 1+ or 1/4, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 2+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 3+, n=109,121,125,120,112,113,112,119	3 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 1+, n=109,121,125,120,112,113,112,119	9 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, T, n=109,121,125,120,112,113,112,119	3 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 3+, n=109,121,125,120,112,113,112,119	3 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, Neg, n=109,121,125,120,112,113,112,119	112 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, Neg, n=109,121,125,120,112,113,112,119	118 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 1+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 2+, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, T, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, T, n=109,121,125,120,112,113,112,119	5 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UN, Neg, n=109,121,125,120,112,113,112,119	113 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, Neg, n=109,121,125,120,112,113,112,119	96 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, 3+ or 1, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UN, Pos, n=109,121,125,120,112,113,112,119	8 Participants
UMEC 15.6 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 1+, n=109,121,125,120,112,113,112,119	8 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 1+, n=109,121,125,120,112,113,112,119	12 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UN, Neg, n=109,121,125,120,112,113,112,119	116 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 2+, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, T or 1/10, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 3+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 3+, n=109,121,125,120,112,113,112,119	2 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, 1+ or 1/4, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, T, n=109,121,125,120,112,113,112,119	5 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, T, n=109,121,125,120,112,113,112,119	6 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, Neg, n=109,121,125,120,112,113,112,119	119 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, T, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, Neg, n=109,121,125,120,112,113,112,119	100 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, 3+ or 1, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, 2+, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, Neg, n=109,121,125,120,112,113,112,119	124 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UB, Neg, n=109,121,125,120,112, 113,112,119	125 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, 1+, n=109,121,125,120,112,113,112,119	6 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, T, n=109,121,125,120,112,113,112,119	14 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 1+, n=109,121,125,120,112,113,112,119	4 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, T, n=109,121,125,120,112,113,112,119	8 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 2+, n=109,121,125,120,112,113,112,119	3 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 2+, n=109,121,125,120,112,113,112,119	5 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, Neg, n=109,121,125,120,112,113,112,119	110 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 3+, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UN, Pos, n=109,121,125,120,112,113,112,119	9 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, Neg, n=109,121,125,120,112,113,112,119	103 Participants
UMEC 31.25 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 1+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 2+, n=109,121,125,120,112,113,112,119	3 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 2+, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, 3+ or 1, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, 1+ or 1/4, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, Neg, n=109,121,125,120,112,113,112,119	90 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, Neg, n=109,121,125,120,112,113,112,119	116 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 1+, n=109,121,125,120,112,113,112,119	12 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 2+, n=109,121,125,120,112,113,112,119	2 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, T or 1/10, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, Neg, n=109,121,125,120,112,113,112,119	116 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UN, Neg, n=109,121,125,120,112,113,112,119	108 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, T, n=109,121,125,120,112,113,112,119	11 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, Neg, n=109,121,125,120,112,113,112,119	100 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, T, n=109,121,125,120,112,113,112,119	2 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 3+, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 3+, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 1+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, Neg, n=109,121,125,120,112,113,112,119	119 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, T, n=109,121,125,120,112,113,112,119	12 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, 1+, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 3+, n=109,121,125,120,112,113,112,119	3 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UB, Neg, n=109,121,125,120,112, 113,112,119	120 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, T, n=109,121,125,120,112,113,112,119	2 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, 2+, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, T, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UN, Pos, n=109,121,125,120,112,113,112,119	12 Participants
UMEC 62.5 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 1+, n=109,121,125,120,112,113,112,119	5 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, T, n=109,121,125,120,112,113,112,119	8 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, Neg, n=109,121,125,120,112,113,112,119	90 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, T, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, T or 1/10, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, Neg, n=109,121,125,120,112,113,112,119	112 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, T, n=109,121,125,120,112,113,112,119	8 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, Neg, n=109,121,125,120,112,113,112,119	104 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, 1+ or 1/4, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, 3+ or 1, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UB, Neg, n=109,121,125,120,112, 113,112,119	112 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, T, n=109,121,125,120,112,113,112,119	13 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 1+, n=109,121,125,120,112,113,112,119	5 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 2+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 3+, n=109,121,125,120,112,113,112,119	4 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 1+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 2+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 3+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UN, Neg, n=109,121,125,120,112,113,112,119	108 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UN, Pos, n=109,121,125,120,112,113,112,119	4 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, Neg, n=109,121,125,120,112,113,112,119	102 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, T, n=109,121,125,120,112,113,112,119	6 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, 1+, n=109,121,125,120,112,113,112,119	4 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, 2+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, Neg, n=109,121,125,120,112,113,112,119	82 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 1+, n=109,121,125,120,112,113,112,119	12 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 2+, n=109,121,125,120,112,113,112,119	5 Participants
UMEC 125 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 3+, n=109,121,125,120,112,113,112,119	5 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, Neg, n=109,121,125,120,112,113,112,119	108 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 1+, n=109,121,125,120,112,113,112,119	7 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, Neg, n=109,121,125,120,112,113,112,119	112 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 1+, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 3+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 1+, n=109,121,125,120,112,113,112,119	12 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, T, n=109,121,125,120,112,113,112,119	3 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, T or 1/10, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 3+, n=109,121,125,120,112,113,112,119	3 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 2+, n=109,121,125,120,112,113,112,119	8 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 3+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 2+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, T, n=109,121,125,120,112,113,112,119	11 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UN, Neg, n=109,121,125,120,112,113,112,119	109 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, 1+, n=109,121,125,120,112,113,112,119	2 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UB, Neg, n=109,121,125,120,112, 113,112,119	112 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 2+, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, 3+ or 1, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, Neg, n=109,121,125,120,112,113,112,119	91 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, 2+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, T, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, T, n=109,121,125,120,112,113,112,119	5 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, 1+ or 1/4, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, Neg, n=109,121,125,120,112,113,112,119	88 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UN, Pos, n=109,121,125,120,112,113,112,119	4 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, Neg, n=109,121,125,120,112,113,112,119	112 Participants
UMEC 250 µg QD	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, T, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 3+, n=109,121,125,120,112,113,112,119	2 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, T, n=109,121,125,120,112,113,112,119	5 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UB, Neg, n=109,121,125,120,112, 113,112,119	112 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UN, Pos, n=109,121,125,120,112,113,112,119	9 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, Neg, n=109,121,125,120,112,113,112,119	111 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, Neg, n=109,121,125,120,112,113,112,119	94 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 1+, n=109,121,125,120,112,113,112,119	5 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, 1+, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 2+, n=109,121,125,120,112,113,112,119	3 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 1+, n=109,121,125,120,112,113,112,119	4 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, 1+ or 1/4, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, T or 1/10, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, Neg, n=109,121,125,120,112,113,112,119	110 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, T, n=109,121,125,120,112,113,112,119	4 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, T, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 3+, n=109,121,125,120,112,113,112,119	3 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, 3+ or 1, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, Neg, n=109,121,125,120,112,113,112,119	107 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 3+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, T, n=109,121,125,120,112,113,112,119	8 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 2+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, T, n=109,121,125,120,112,113,112,119	2 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, 2+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 1+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 2+, n=109,121,125,120,112,113,112,119	11 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, Neg, n=109,121,125,120,112,113,112,119	89 Participants
UMEC 15.6 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UN, Neg, n=109,121,125,120,112,113,112,119	103 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 2+, n=109,121,125,120,112,113,112,119	2 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 3+, n=109,121,125,120,112,113,112,119	3 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 2+, n=109,121,125,120,112,113,112,119	12 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UN, Pos, n=109,121,125,120,112,113,112,119	14 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 2+, n=109,121,125,120,112,113,112,119	2 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, Neg, n=109,121,125,120,112,113,112,119	111 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, 1+, n=109,121,125,120,112,113,112,119	2 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, T, n=109,121,125,120,112,113,112,119	13 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UOB, Neg, n=109,121,125,120,112,113,112,119	99 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, T, n=109,121,125,120,112,113,112,119	4 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UB, Neg, n=109,121,125,120,112, 113,112,119	119 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, 1+, n=109,121,125,120,112,113,112,119	4 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, 3+ or 1, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UP, 2+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, 1+ or 1/4, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, Neg, n=109,121,125,120,112,113,112,119	113 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 3+, n=109,121,125,120,112,113,112,119	1 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, Neg, n=109,121,125,120,112,113,112,119	85 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, T, n=109,121,125,120,112,113,112,119	3 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, T, n=109,121,125,120,112,113,112,119	11 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, Neg, n=109,121,125,120,112,113,112,119	119 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, T or 1/10, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UWBC, 1+, n=109,121,125,120,112,113,112,119	10 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UG, T, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UN, Neg, n=109,121,125,120,112,113,112,119	105 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 3+, n=109,121,125,120,112,113,112,119	0 Participants
UMEC 31.25 µg BID	Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period	UK, 1+, n=109,121,125,120,112,113,112,119	1 Participants

Primary

Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An 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, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of SAEs.

Time frame: From Baseline until the end of Treatment Period 3 (up to Study Day 70)

Population: ITT Population

Arm	Measure	Group	Value (NUMBER)
All Study Treatments	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)	Any SAE	0 Participants
All Study Treatments	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)	Any AE	15 Participants
UMEC 15.6 µg QD	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)	Any SAE	0 Participants
UMEC 15.6 µg QD	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)	Any AE	12 Participants
UMEC 31.25 µg QD	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)	Any SAE	0 Participants
UMEC 31.25 µg QD	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)	Any AE	13 Participants
UMEC 62.5 µg QD	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)	Any AE	21 Participants
UMEC 62.5 µg QD	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)	Any SAE	0 Participants
UMEC 125 µg QD	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)	Any AE	26 Participants
UMEC 125 µg QD	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)	Any SAE	0 Participants
UMEC 250 µg QD	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)	Any AE	28 Participants
UMEC 250 µg QD	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)	Any SAE	1 Participants
UMEC 15.6 µg BID	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)	Any AE	16 Participants
UMEC 15.6 µg BID	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)	Any SAE	0 Participants
UMEC 31.25 µg BID	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)	Any SAE	0 Participants
UMEC 31.25 µg BID	Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)	Any AE	12 Participants

Primary

Number of Participants With Asthma Exacerbations During the Treatment Period

Worsening of asthma symptoms is monitored throughout the study. Severe exacerbation (deterioration of asthma requiring use of systemic corticosteroids for 3 days, inpatient hospitalization or emergency department visit due to asthma) is an exclusion criterion and requires withdrawal from the study. Asthma symptoms were assessed daily using an electronic diary throughout study.

Time frame: From Baseline until the end of Treatment Period 3 (up to Study Day 70)

Population: ITT Population. Only those participants with data available at the specified time points were analyzed.

Arm	Measure	Value (NUMBER)
All Study Treatments	Number of Participants With Asthma Exacerbations During the Treatment Period	2 Participants
UMEC 15.6 µg QD	Number of Participants With Asthma Exacerbations During the Treatment Period	0 Participants
UMEC 31.25 µg QD	Number of Participants With Asthma Exacerbations During the Treatment Period	0 Participants
UMEC 62.5 µg QD	Number of Participants With Asthma Exacerbations During the Treatment Period	0 Participants
UMEC 125 µg QD	Number of Participants With Asthma Exacerbations During the Treatment Period	0 Participants
UMEC 250 µg QD	Number of Participants With Asthma Exacerbations During the Treatment Period	0 Participants
UMEC 15.6 µg BID	Number of Participants With Asthma Exacerbations During the Treatment Period	1 Participants
UMEC 31.25 µg BID	Number of Participants With Asthma Exacerbations During the Treatment Period	1 Participants

Primary

Number of Participants With the Indicated 24 Hour Holter Findings

Twenty-four hour Holter ECG measurements were obtained using a 12-lead Holter monitor. The Holter monitor is worn by the participant for 24 hours, and the monitor continuously records the heart's rhythm while the monitor is worn. Following the 24-hour period, the data from the monitor were downloaded and transmitted to the centralized vendor for analysis and interpretation by a licensed cardiologist. The 24-hour Holter ECG measurements were obtained at during the screening period and on Day 14 of each treatment period. The number of participants with clinically significant change (abnormal or normal) were reported.

Time frame: Day 14 of each treatment period (up to Study Day 70)

Population: ITT Population. Only participants with sufficient data (at least 16 hours of recorded data) at the specified time points were analyzed.

Arm	Measure	Group	Value (NUMBER)
All Study Treatments	Number of Participants With the Indicated 24 Hour Holter Findings	Abnormal	6 Participants
All Study Treatments	Number of Participants With the Indicated 24 Hour Holter Findings	Normal	35 Participants
UMEC 15.6 µg QD	Number of Participants With the Indicated 24 Hour Holter Findings	Abnormal	3 Participants
UMEC 15.6 µg QD	Number of Participants With the Indicated 24 Hour Holter Findings	Normal	38 Participants
UMEC 31.25 µg QD	Number of Participants With the Indicated 24 Hour Holter Findings	Abnormal	7 Participants
UMEC 31.25 µg QD	Number of Participants With the Indicated 24 Hour Holter Findings	Normal	44 Participants
UMEC 62.5 µg QD	Number of Participants With the Indicated 24 Hour Holter Findings	Abnormal	7 Participants
UMEC 62.5 µg QD	Number of Participants With the Indicated 24 Hour Holter Findings	Normal	39 Participants
UMEC 125 µg QD	Number of Participants With the Indicated 24 Hour Holter Findings	Abnormal	8 Participants
UMEC 125 µg QD	Number of Participants With the Indicated 24 Hour Holter Findings	Normal	38 Participants
UMEC 250 µg QD	Number of Participants With the Indicated 24 Hour Holter Findings	Abnormal	8 Participants
UMEC 250 µg QD	Number of Participants With the Indicated 24 Hour Holter Findings	Normal	34 Participants
UMEC 15.6 µg BID	Number of Participants With the Indicated 24 Hour Holter Findings	Normal	32 Participants
UMEC 15.6 µg BID	Number of Participants With the Indicated 24 Hour Holter Findings	Abnormal	7 Participants
UMEC 31.25 µg BID	Number of Participants With the Indicated 24 Hour Holter Findings	Abnormal	7 Participants
UMEC 31.25 µg BID	Number of Participants With the Indicated 24 Hour Holter Findings	Normal	42 Participants

Primary

Number of Participants With the Indicated Abnormal Electrocardiogram Findings

Electrocardiograph measurements performed at Screening (Visit 1) and at Day 1 and Day 14 (pre-dose, 10 minutes post-dose and 2 hours post-dose.of each treatment period). Any clinically significant findings were identified during participant monitoring.

Time frame: Day 14 of each treatment period (up to Study Day 70)

Population: ITT Population. Only those participants remaining in the study and contributing evaluable data at the indicated time points were analyzed.

Arm	Measure	Group	Value (NUMBER)
All Study Treatments	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Depolarisation/Repolarisation(QRS-T)	21 Participants
All Study Treatments	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Rhythm	12 Participants
All Study Treatments	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Myocardial Infarction	2 Participants
All Study Treatments	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	P-Wave and QRS Morphology	0 Participants
All Study Treatments	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Conduction	14 Participants
UMEC 15.6 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Myocardial Infarction	3 Participants
UMEC 15.6 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Conduction	17 Participants
UMEC 15.6 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Rhythm	13 Participants
UMEC 15.6 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Depolarisation/Repolarisation(QRS-T)	20 Participants
UMEC 15.6 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	P-Wave and QRS Morphology	0 Participants
UMEC 31.25 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Depolarisation/Repolarisation(QRS-T)	26 Participants
UMEC 31.25 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	P-Wave and QRS Morphology	0 Participants
UMEC 31.25 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Rhythm	15 Participants
UMEC 31.25 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Myocardial Infarction	1 Participants
UMEC 31.25 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Conduction	10 Participants
UMEC 62.5 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Rhythm	12 Participants
UMEC 62.5 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Myocardial Infarction	2 Participants
UMEC 62.5 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Depolarisation/Repolarisation(QRS-T)	20 Participants
UMEC 62.5 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	P-Wave and QRS Morphology	0 Participants
UMEC 62.5 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Conduction	12 Participants
UMEC 125 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	P-Wave and QRS Morphology	1 Participants
UMEC 125 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Conduction	10 Participants
UMEC 125 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Depolarisation/Repolarisation(QRS-T)	32 Participants
UMEC 125 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Myocardial Infarction	1 Participants
UMEC 125 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Rhythm	13 Participants
UMEC 250 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	P-Wave and QRS Morphology	0 Participants
UMEC 250 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Depolarisation/Repolarisation(QRS-T)	25 Participants
UMEC 250 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Rhythm	15 Participants
UMEC 250 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Myocardial Infarction	0 Participants
UMEC 250 µg QD	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Conduction	11 Participants
UMEC 15.6 µg BID	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	P-Wave and QRS Morphology	2 Participants
UMEC 15.6 µg BID	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Conduction	7 Participants
UMEC 15.6 µg BID	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Depolarisation/Repolarisation(QRS-T)	22 Participants
UMEC 15.6 µg BID	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Rhythm	17 Participants
UMEC 15.6 µg BID	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Myocardial Infarction	1 Participants
UMEC 31.25 µg BID	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Conduction	12 Participants
UMEC 31.25 µg BID	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Depolarisation/Repolarisation(QRS-T)	28 Participants
UMEC 31.25 µg BID	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	P-Wave and QRS Morphology	0 Participants
UMEC 31.25 µg BID	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Myocardial Infarction	2 Participants
UMEC 31.25 µg BID	Number of Participants With the Indicated Abnormal Electrocardiogram Findings	Rhythm	21 Participants

Primary

Urine pH on Day 14 of Each Treatment Period

Urine samples were collected for the measurement of urine pH by dipstick method at Day 14. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).

Time frame: Day 14 of each treatment period (up to Study Day 70)

Population: ITT Population. Only those participants with data available at the specified time points were analyzed.

Arm	Measure	Value (MEAN)	Dispersion
All Study Treatments	Urine pH on Day 14 of Each Treatment Period	5.89 Scores on a scale	Standard Deviation 0.635
UMEC 15.6 µg QD	Urine pH on Day 14 of Each Treatment Period	5.97 Scores on a scale	Standard Deviation 0.709
UMEC 31.25 µg QD	Urine pH on Day 14 of Each Treatment Period	6.05 Scores on a scale	Standard Deviation 0.718
UMEC 62.5 µg QD	Urine pH on Day 14 of Each Treatment Period	6.07 Scores on a scale	Standard Deviation 0.743
UMEC 125 µg QD	Urine pH on Day 14 of Each Treatment Period	5.90 Scores on a scale	Standard Deviation 0.678
UMEC 250 µg QD	Urine pH on Day 14 of Each Treatment Period	5.99 Scores on a scale	Standard Deviation 0.72
UMEC 15.6 µg BID	Urine pH on Day 14 of Each Treatment Period	5.89 Scores on a scale	Standard Deviation 0.69
UMEC 31.25 µg BID	Urine pH on Day 14 of Each Treatment Period	5.90 Scores on a scale	Standard Deviation 0.684

Primary

Urine Specific Gravity on Day 14 of Each Treatment Period

Urine samples were collected for the measurement of urine specific gravity by dipstick method at Day 14. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. A urinary specific gravity measurement is a routine part of urinalysis. The reference range is 1.002-1.030.

Time frame: Day 14 of each treatment period (up to Study Day 70)

Population: ITT Population. Only those participants with data available at the specified time points were analyzed.

Arm	Measure	Value (MEAN)	Dispersion
All Study Treatments	Urine Specific Gravity on Day 14 of Each Treatment Period	1.0194 Ratio	Standard Deviation 0.00703
UMEC 15.6 µg QD	Urine Specific Gravity on Day 14 of Each Treatment Period	1.0198 Ratio	Standard Deviation 0.00628
UMEC 31.25 µg QD	Urine Specific Gravity on Day 14 of Each Treatment Period	1.0194 Ratio	Standard Deviation 0.00732
UMEC 62.5 µg QD	Urine Specific Gravity on Day 14 of Each Treatment Period	1.0185 Ratio	Standard Deviation 0.00653
UMEC 125 µg QD	Urine Specific Gravity on Day 14 of Each Treatment Period	1.0201 Ratio	Standard Deviation 0.0078
UMEC 250 µg QD	Urine Specific Gravity on Day 14 of Each Treatment Period	1.0192 Ratio	Standard Deviation 0.00707
UMEC 15.6 µg BID	Urine Specific Gravity on Day 14 of Each Treatment Period	1.0189 Ratio	Standard Deviation 0.00734
UMEC 31.25 µg BID	Urine Specific Gravity on Day 14 of Each Treatment Period	1.0193 Ratio	Standard Deviation 0.00671

Secondary

Change From Baseline (BL) in the Weighted Mean (WM) 0-24 Hour FEV1 Obtained Post-AM Dose on Day 14 of Each Treatment Period

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The WM FEV1 was derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. Baseline is the 0h value obtained prior to the AM dose on Day 14 of the treatment period. Change from BL at a was calculated as WM at the evaluated time point minus BL. Analysis was performed using a mixed model, including treatment, period, period Baseline FEV1, and mean Baseline FEV1 as fixed effects and participant as a random effect.

Time frame: Baseline and Day 14 of each treatment period (up to Study Day 70)

Population: ITT Population. Only those participants with data available at the specified time points were analyzed.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
All Study Treatments	Change From Baseline (BL) in the Weighted Mean (WM) 0-24 Hour FEV1 Obtained Post-AM Dose on Day 14 of Each Treatment Period	-0.025 Liters	Standard Error 0.0255
UMEC 15.6 µg QD	Change From Baseline (BL) in the Weighted Mean (WM) 0-24 Hour FEV1 Obtained Post-AM Dose on Day 14 of Each Treatment Period	0.060 Liters	Standard Error 0.0249
UMEC 31.25 µg QD	Change From Baseline (BL) in the Weighted Mean (WM) 0-24 Hour FEV1 Obtained Post-AM Dose on Day 14 of Each Treatment Period	0.077 Liters	Standard Error 0.0222
UMEC 62.5 µg QD	Change From Baseline (BL) in the Weighted Mean (WM) 0-24 Hour FEV1 Obtained Post-AM Dose on Day 14 of Each Treatment Period	0.092 Liters	Standard Error 0.0232
UMEC 125 µg QD	Change From Baseline (BL) in the Weighted Mean (WM) 0-24 Hour FEV1 Obtained Post-AM Dose on Day 14 of Each Treatment Period	0.094 Liters	Standard Error 0.0229
UMEC 250 µg QD	Change From Baseline (BL) in the Weighted Mean (WM) 0-24 Hour FEV1 Obtained Post-AM Dose on Day 14 of Each Treatment Period	0.048 Liters	Standard Error 0.0243
UMEC 15.6 µg BID	Change From Baseline (BL) in the Weighted Mean (WM) 0-24 Hour FEV1 Obtained Post-AM Dose on Day 14 of Each Treatment Period	0.097 Liters	Standard Error 0.0252
UMEC 31.25 µg BID	Change From Baseline (BL) in the Weighted Mean (WM) 0-24 Hour FEV1 Obtained Post-AM Dose on Day 14 of Each Treatment Period	0.043 Liters	Standard Error 0.0231

Secondary

Change From Baseline in Mean Morning (AM) and Evening (PM) Pre-treatment Peak Expiratory Flow (PEF) Over Day 7 to Day 14 of Each Treatment Period

PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants daily in the morning and evening just prior to each dose, using an electronic peak flow meter, throughout the 14-day Treatment Period. Only the averaged daily AM and PM PEF over Days 7 to 14 was analyzed. The analysis was performed using a mixed effects analysis of covariance model with fixed effect terms for treatment and period; Baseline PEF AM and PM, gender and age fitted as covariates; and participant as a random effect.

Time frame: Baseline (Day 7 prior to each treatment period) and the last 7 days of each treatment period (up to Study Day 70)

Arm	Measure	Group	Value (MEAN)	Dispersion
All Study Treatments	Change From Baseline in Mean Morning (AM) and Evening (PM) Pre-treatment Peak Expiratory Flow (PEF) Over Day 7 to Day 14 of Each Treatment Period	AM, n=112, 120, 125, 122, 113, 116, 110, 122	0.8 Liters per minute	Standard Deviation 31.98
All Study Treatments	Change From Baseline in Mean Morning (AM) and Evening (PM) Pre-treatment Peak Expiratory Flow (PEF) Over Day 7 to Day 14 of Each Treatment Period	PM, n=116, 123, 123, 119, 115, 118, 108, 121	-5.1 Liters per minute	Standard Deviation 34.43
UMEC 15.6 µg QD	Change From Baseline in Mean Morning (AM) and Evening (PM) Pre-treatment Peak Expiratory Flow (PEF) Over Day 7 to Day 14 of Each Treatment Period	AM, n=112, 120, 125, 122, 113, 116, 110, 122	5.2 Liters per minute	Standard Deviation 42.17
UMEC 15.6 µg QD	Change From Baseline in Mean Morning (AM) and Evening (PM) Pre-treatment Peak Expiratory Flow (PEF) Over Day 7 to Day 14 of Each Treatment Period	PM, n=116, 123, 123, 119, 115, 118, 108, 121	10.0 Liters per minute	Standard Deviation 43.47
UMEC 31.25 µg QD	Change From Baseline in Mean Morning (AM) and Evening (PM) Pre-treatment Peak Expiratory Flow (PEF) Over Day 7 to Day 14 of Each Treatment Period	AM, n=112, 120, 125, 122, 113, 116, 110, 122	1.7 Liters per minute	Standard Deviation 37.95
UMEC 31.25 µg QD	Change From Baseline in Mean Morning (AM) and Evening (PM) Pre-treatment Peak Expiratory Flow (PEF) Over Day 7 to Day 14 of Each Treatment Period	PM, n=116, 123, 123, 119, 115, 118, 108, 121	1.5 Liters per minute	Standard Deviation 37.95
UMEC 62.5 µg QD	Change From Baseline in Mean Morning (AM) and Evening (PM) Pre-treatment Peak Expiratory Flow (PEF) Over Day 7 to Day 14 of Each Treatment Period	AM, n=112, 120, 125, 122, 113, 116, 110, 122	1.1 Liters per minute	Standard Deviation 31.23
UMEC 62.5 µg QD	Change From Baseline in Mean Morning (AM) and Evening (PM) Pre-treatment Peak Expiratory Flow (PEF) Over Day 7 to Day 14 of Each Treatment Period	PM, n=116, 123, 123, 119, 115, 118, 108, 121	-0.9 Liters per minute	Standard Deviation 31.32
UMEC 125 µg QD	Change From Baseline in Mean Morning (AM) and Evening (PM) Pre-treatment Peak Expiratory Flow (PEF) Over Day 7 to Day 14 of Each Treatment Period	AM, n=112, 120, 125, 122, 113, 116, 110, 122	6.4 Liters per minute	Standard Deviation 32.31
UMEC 125 µg QD	Change From Baseline in Mean Morning (AM) and Evening (PM) Pre-treatment Peak Expiratory Flow (PEF) Over Day 7 to Day 14 of Each Treatment Period	PM, n=116, 123, 123, 119, 115, 118, 108, 121	9.8 Liters per minute	Standard Deviation 31.25
UMEC 250 µg QD	Change From Baseline in Mean Morning (AM) and Evening (PM) Pre-treatment Peak Expiratory Flow (PEF) Over Day 7 to Day 14 of Each Treatment Period	AM, n=112, 120, 125, 122, 113, 116, 110, 122	6.4 Liters per minute	Standard Deviation 43.24
UMEC 250 µg QD	Change From Baseline in Mean Morning (AM) and Evening (PM) Pre-treatment Peak Expiratory Flow (PEF) Over Day 7 to Day 14 of Each Treatment Period	PM, n=116, 123, 123, 119, 115, 118, 108, 121	9.3 Liters per minute	Standard Deviation 40.03
UMEC 15.6 µg BID	Change From Baseline in Mean Morning (AM) and Evening (PM) Pre-treatment Peak Expiratory Flow (PEF) Over Day 7 to Day 14 of Each Treatment Period	PM, n=116, 123, 123, 119, 115, 118, 108, 121	2.5 Liters per minute	Standard Deviation 35.89
UMEC 15.6 µg BID	Change From Baseline in Mean Morning (AM) and Evening (PM) Pre-treatment Peak Expiratory Flow (PEF) Over Day 7 to Day 14 of Each Treatment Period	AM, n=112, 120, 125, 122, 113, 116, 110, 122	5.0 Liters per minute	Standard Deviation 35.82
UMEC 31.25 µg BID	Change From Baseline in Mean Morning (AM) and Evening (PM) Pre-treatment Peak Expiratory Flow (PEF) Over Day 7 to Day 14 of Each Treatment Period	AM, n=112, 120, 125, 122, 113, 116, 110, 122	5.8 Liters per minute	Standard Deviation 33
UMEC 31.25 µg BID	Change From Baseline in Mean Morning (AM) and Evening (PM) Pre-treatment Peak Expiratory Flow (PEF) Over Day 7 to Day 14 of Each Treatment Period	PM, n=116, 123, 123, 119, 115, 118, 108, 121	8.7 Liters per minute	Standard Deviation 30.55

Secondary

Change From Baseline in the Mean Number of Puffs Per Day of Rescue Albuterol/Salbutamol Over Day 7 to Day 14 of Each Treatment Period

The mean number of puffs per day of rescue salbutamol at Baseline (i.e. run-in or washout data) and on-treatment were recorded. Total puffs was calculated as (Number of Puffs + (2 x number of Nebules)). Only the 7 days proceeding each treatment period were included in the Baseline calculations. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Time frame: Baseline (Day 7 prior to each treatment period) and the last 7 days of each treatment period (up to Study Day 70)

Population: ITT Population. Only those participants with data available at the specified time points were analyzed.

Arm	Measure	Value (MEAN)	Dispersion
All Study Treatments	Change From Baseline in the Mean Number of Puffs Per Day of Rescue Albuterol/Salbutamol Over Day 7 to Day 14 of Each Treatment Period	-0.3 Number of puffs	Standard Deviation 1.25
UMEC 15.6 µg QD	Change From Baseline in the Mean Number of Puffs Per Day of Rescue Albuterol/Salbutamol Over Day 7 to Day 14 of Each Treatment Period	-0.4 Number of puffs	Standard Deviation 1.42
UMEC 31.25 µg QD	Change From Baseline in the Mean Number of Puffs Per Day of Rescue Albuterol/Salbutamol Over Day 7 to Day 14 of Each Treatment Period	-0.2 Number of puffs	Standard Deviation 1.06
UMEC 62.5 µg QD	Change From Baseline in the Mean Number of Puffs Per Day of Rescue Albuterol/Salbutamol Over Day 7 to Day 14 of Each Treatment Period	-0.3 Number of puffs	Standard Deviation 1.14
UMEC 125 µg QD	Change From Baseline in the Mean Number of Puffs Per Day of Rescue Albuterol/Salbutamol Over Day 7 to Day 14 of Each Treatment Period	-0.4 Number of puffs	Standard Deviation 1.19
UMEC 250 µg QD	Change From Baseline in the Mean Number of Puffs Per Day of Rescue Albuterol/Salbutamol Over Day 7 to Day 14 of Each Treatment Period	-0.3 Number of puffs	Standard Deviation 1.31
UMEC 15.6 µg BID	Change From Baseline in the Mean Number of Puffs Per Day of Rescue Albuterol/Salbutamol Over Day 7 to Day 14 of Each Treatment Period	-0.6 Number of puffs	Standard Deviation 1.49
UMEC 31.25 µg BID	Change From Baseline in the Mean Number of Puffs Per Day of Rescue Albuterol/Salbutamol Over Day 7 to Day 14 of Each Treatment Period	-0.3 Number of puffs	Standard Deviation 1.04

Secondary

Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period

Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry. Serial FEV1 was measured at 5, 15, 30 minutes (min), 1, 3, 6, 9, 12, 16, 20, 23 and 24 hours (h) post-dose. Baseline is the 0h value obtained prior to the AM dose on Day 14 of the treatment period. Change from Baseline was calculated as FEV1 value at the evaluated time point minus Baseline. Analysis was preformed using a repeated measures model with terms for period, treatment, time, mean Baseline, period Baseline, and time by mean Baseline, time by period Baseline, and time by treatment interactions.

Time frame: Baseline and Day 14 of each treatment period (up to Study Day 70)

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
All Study Treatments	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	5 min, n=41, 39, 49, 46, 44, 42, 38, 48	0.024 Liters	Standard Error 0.0329
All Study Treatments	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	1 h, n=41, 41, 51, 46, 46, 42, 39, 49	0.025 Liters	Standard Error 0.0319
All Study Treatments	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	12 h, n=41, 41, 51, 46, 46, 41, 39, 49	-0.044 Liters	Standard Error 0.0395
All Study Treatments	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	3 h, n=41, 41, 51, 46, 46, 42, 39, 49	0.000 Liters	Standard Error 0.0353
All Study Treatments	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	20 h, n=40, 41, 51, 45, 46, 41, 39, 49	-0.149 Liters	Standard Error 0.0441
All Study Treatments	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	15 min, n=41, 41, 51, 46, 46, 42, 39, 49	0.002 Liters	Standard Error 0.0322
All Study Treatments	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	9 h, n=41, 40, 51, 46, 46, 42, 39, 49	-0.049 Liters	Standard Error 0.0354
All Study Treatments	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	24 h, n=41, 41, 51, 45, 46, 42, 39, 49	0.039 Liters	Standard Error 0.0387
All Study Treatments	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	6 h, n=41, 40, 51, 46, 46, 42, 39, 48	0.007 Liters	Standard Error 0.0368
All Study Treatments	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	16 h, n=40, 40, 51, 46, 46, 42, 38, 49	-0.074 Liters	Standard Error 0.0408
All Study Treatments	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	30 min, n=45, 42, 39, 49, 45, 42, 39, 49	0.012 Liters	Standard Error 0.0318
All Study Treatments	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	23 h, n=40, 40, 51, 46, 46, 42, 39, 48	0.013 Liters	Standard Error 0.0391
UMEC 15.6 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	6 h, n=41, 40, 51, 46, 46, 42, 39, 48	0.099 Liters	Standard Error 0.0369
UMEC 15.6 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	5 min, n=41, 39, 49, 46, 44, 42, 38, 48	0.095 Liters	Standard Error 0.033
UMEC 15.6 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	1 h, n=41, 41, 51, 46, 46, 42, 39, 49	0.127 Liters	Standard Error 0.0318
UMEC 15.6 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	9 h, n=41, 40, 51, 46, 46, 42, 39, 49	0.043 Liters	Standard Error 0.0356
UMEC 15.6 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	3 h, n=41, 41, 51, 46, 46, 42, 39, 49	0.141 Liters	Standard Error 0.0353
UMEC 15.6 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	16 h, n=40, 40, 51, 46, 46, 42, 38, 49	0.006 Liters	Standard Error 0.0407
UMEC 15.6 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	24 h, n=41, 41, 51, 45, 46, 42, 39, 49	0.105 Liters	Standard Error 0.0386
UMEC 15.6 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	20 h, n=40, 41, 51, 45, 46, 41, 39, 49	-0.046 Liters	Standard Error 0.0438
UMEC 15.6 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	12 h, n=41, 41, 51, 46, 46, 41, 39, 49	0.015 Liters	Standard Error 0.0394
UMEC 15.6 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	23 h, n=40, 40, 51, 46, 46, 42, 39, 48	0.033 Liters	Standard Error 0.039
UMEC 15.6 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	15 min, n=41, 41, 51, 46, 46, 42, 39, 49	0.082 Liters	Standard Error 0.0322
UMEC 15.6 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	30 min, n=45, 42, 39, 49, 45, 42, 39, 49	0.109 Liters	Standard Error 0.0317
UMEC 31.25 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	3 h, n=41, 41, 51, 46, 46, 42, 39, 49	0.175 Liters	Standard Error 0.0317
UMEC 31.25 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	9 h, n=41, 40, 51, 46, 46, 42, 39, 49	0.061 Liters	Standard Error 0.0318
UMEC 31.25 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	24 h, n=41, 41, 51, 45, 46, 42, 39, 49	0.110 Liters	Standard Error 0.0347
UMEC 31.25 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	15 min, n=41, 41, 51, 46, 46, 42, 39, 49	0.124 Liters	Standard Error 0.029
UMEC 31.25 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	23 h, n=40, 40, 51, 46, 46, 42, 39, 48	0.056 Liters	Standard Error 0.0349
UMEC 31.25 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	30 min, n=45, 42, 39, 49, 45, 42, 39, 49	0.115 Liters	Standard Error 0.0285
UMEC 31.25 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	5 min, n=41, 39, 49, 46, 44, 42, 38, 48	0.110 Liters	Standard Error 0.0296
UMEC 31.25 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	1 h, n=41, 41, 51, 46, 46, 42, 39, 49	0.161 Liters	Standard Error 0.0286
UMEC 31.25 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	20 h, n=40, 41, 51, 45, 46, 41, 39, 49	-0.003 Liters	Standard Error 0.0393
UMEC 31.25 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	12 h, n=41, 41, 51, 46, 46, 41, 39, 49	0.021 Liters	Standard Error 0.0354
UMEC 31.25 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	16 h, n=40, 40, 51, 46, 46, 42, 38, 49	0.022 Liters	Standard Error 0.0364
UMEC 31.25 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	6 h, n=41, 40, 51, 46, 46, 42, 39, 48	0.089 Liters	Standard Error 0.033
UMEC 62.5 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	3 h, n=41, 41, 51, 46, 46, 42, 39, 49	0.156 Liters	Standard Error 0.0332
UMEC 62.5 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	20 h, n=40, 41, 51, 45, 46, 41, 39, 49	0.057 Liters	Standard Error 0.0415
UMEC 62.5 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	16 h, n=40, 40, 51, 46, 46, 42, 38, 49	0.052 Liters	Standard Error 0.0382
UMEC 62.5 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	9 h, n=41, 40, 51, 46, 46, 42, 39, 49	0.118 Liters	Standard Error 0.0333
UMEC 62.5 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	30 min, n=45, 42, 39, 49, 45, 42, 39, 49	0.092 Liters	Standard Error 0.0299
UMEC 62.5 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	23 h, n=40, 40, 51, 46, 46, 42, 39, 48	0.107 Liters	Standard Error 0.0366
UMEC 62.5 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	15 min, n=41, 41, 51, 46, 46, 42, 39, 49	0.090 Liters	Standard Error 0.0303
UMEC 62.5 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	12 h, n=41, 41, 51, 46, 46, 41, 39, 49	0.060 Liters	Standard Error 0.0372
UMEC 62.5 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	6 h, n=41, 40, 51, 46, 46, 42, 39, 48	0.108 Liters	Standard Error 0.0346
UMEC 62.5 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	5 min, n=41, 39, 49, 46, 44, 42, 38, 48	0.077 Liters	Standard Error 0.0309
UMEC 62.5 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	1 h, n=41, 41, 51, 46, 46, 42, 39, 49	0.143 Liters	Standard Error 0.03
UMEC 62.5 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	24 h, n=41, 41, 51, 45, 46, 42, 39, 49	0.143 Liters	Standard Error 0.0366
UMEC 125 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	16 h, n=40, 40, 51, 46, 46, 42, 38, 49	0.035 Liters	Standard Error 0.0384
UMEC 125 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	5 min, n=41, 39, 49, 46, 44, 42, 38, 48	0.123 Liters	Standard Error 0.0312
UMEC 125 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	15 min, n=41, 41, 51, 46, 46, 42, 39, 49	0.115 Liters	Standard Error 0.0305
UMEC 125 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	30 min, n=45, 42, 39, 49, 45, 42, 39, 49	0.149 Liters	Standard Error 0.0301
UMEC 125 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	1 h, n=41, 41, 51, 46, 46, 42, 39, 49	0.165 Liters	Standard Error 0.0302
UMEC 125 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	3 h, n=41, 41, 51, 46, 46, 42, 39, 49	0.143 Liters	Standard Error 0.0335
UMEC 125 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	6 h, n=41, 40, 51, 46, 46, 42, 39, 48	0.134 Liters	Standard Error 0.0349
UMEC 125 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	9 h, n=41, 40, 51, 46, 46, 42, 39, 49	0.117 Liters	Standard Error 0.0335
UMEC 125 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	12 h, n=41, 41, 51, 46, 46, 41, 39, 49	0.056 Liters	Standard Error 0.0374
UMEC 125 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	20 h, n=40, 41, 51, 45, 46, 41, 39, 49	0.029 Liters	Standard Error 0.0416
UMEC 125 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	23 h, n=40, 40, 51, 46, 46, 42, 39, 48	0.087 Liters	Standard Error 0.0369
UMEC 125 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	24 h, n=41, 41, 51, 45, 46, 42, 39, 49	0.139 Liters	Standard Error 0.0366
UMEC 250 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	30 min, n=45, 42, 39, 49, 45, 42, 39, 49	0.040 Liters	Standard Error 0.0315
UMEC 250 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	5 min, n=41, 39, 49, 46, 44, 42, 38, 48	0.042 Liters	Standard Error 0.0326
UMEC 250 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	1 h, n=41, 41, 51, 46, 46, 42, 39, 49	0.113 Liters	Standard Error 0.0316
UMEC 250 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	20 h, n=40, 41, 51, 45, 46, 41, 39, 49	-0.050 Liters	Standard Error 0.0437
UMEC 250 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	24 h, n=41, 41, 51, 45, 46, 42, 39, 49	0.088 Liters	Standard Error 0.0384
UMEC 250 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	6 h, n=41, 40, 51, 46, 46, 42, 39, 48	0.076 Liters	Standard Error 0.0365
UMEC 250 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	15 min, n=41, 41, 51, 46, 46, 42, 39, 49	0.038 Liters	Standard Error 0.032
UMEC 250 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	12 h, n=41, 41, 51, 46, 46, 41, 39, 49	0.016 Liters	Standard Error 0.0393
UMEC 250 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	3 h, n=41, 41, 51, 46, 46, 42, 39, 49	0.143 Liters	Standard Error 0.035
UMEC 250 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	16 h, n=40, 40, 51, 46, 46, 42, 38, 49	0.008 Liters	Standard Error 0.0402
UMEC 250 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	9 h, n=41, 40, 51, 46, 46, 42, 39, 49	0.081 Liters	Standard Error 0.0351
UMEC 250 µg QD	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	23 h, n=40, 40, 51, 46, 46, 42, 39, 48	0.058 Liters	Standard Error 0.0386
UMEC 15.6 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	6 h, n=41, 40, 51, 46, 46, 42, 39, 48	0.157 Liters	Standard Error 0.0378
UMEC 15.6 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	12 h, n=41, 41, 51, 46, 46, 41, 39, 49	0.050 Liters	Standard Error 0.0405
UMEC 15.6 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	3 h, n=41, 41, 51, 46, 46, 42, 39, 49	0.182 Liters	Standard Error 0.0362
UMEC 15.6 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	16 h, n=40, 40, 51, 46, 46, 42, 38, 49	0.053 Liters	Standard Error 0.0419
UMEC 15.6 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	1 h, n=41, 41, 51, 46, 46, 42, 39, 49	0.164 Liters	Standard Error 0.0327
UMEC 15.6 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	20 h, n=40, 41, 51, 45, 46, 41, 39, 49	-0.005 Liters	Standard Error 0.045
UMEC 15.6 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	30 min, n=45, 42, 39, 49, 45, 42, 39, 49	0.158 Liters	Standard Error 0.0326
UMEC 15.6 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	15 min, n=41, 41, 51, 46, 46, 42, 39, 49	0.160 Liters	Standard Error 0.0331
UMEC 15.6 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	24 h, n=41, 41, 51, 45, 46, 42, 39, 49	0.187 Liters	Standard Error 0.0397
UMEC 15.6 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	23 h, n=40, 40, 51, 46, 46, 42, 39, 48	0.081 Liters	Standard Error 0.0399
UMEC 15.6 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	5 min, n=41, 39, 49, 46, 44, 42, 38, 48	0.141 Liters	Standard Error 0.0338
UMEC 15.6 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	9 h, n=41, 40, 51, 46, 46, 42, 39, 49	0.072 Liters	Standard Error 0.0363
UMEC 31.25 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	9 h, n=41, 40, 51, 46, 46, 42, 39, 49	0.075 Liters	Standard Error 0.0323
UMEC 31.25 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	16 h, n=40, 40, 51, 46, 46, 42, 38, 49	0.009 Liters	Standard Error 0.037
UMEC 31.25 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	6 h, n=41, 40, 51, 46, 46, 42, 39, 48	0.100 Liters	Standard Error 0.0337
UMEC 31.25 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	23 h, n=40, 40, 51, 46, 46, 42, 39, 48	0.037 Liters	Standard Error 0.0356
UMEC 31.25 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	3 h, n=41, 41, 51, 46, 46, 42, 39, 49	0.165 Liters	Standard Error 0.0322
UMEC 31.25 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	30 min, n=45, 42, 39, 49, 45, 42, 39, 49	0.110 Liters	Standard Error 0.029
UMEC 31.25 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	5 min, n=41, 39, 49, 46, 44, 42, 38, 48	0.118 Liters	Standard Error 0.0301
UMEC 31.25 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	20 h, n=40, 41, 51, 45, 46, 41, 39, 49	-0.012 Liters	Standard Error 0.04
UMEC 31.25 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	24 h, n=41, 41, 51, 45, 46, 42, 39, 49	0.124 Liters	Standard Error 0.0353
UMEC 31.25 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	1 h, n=41, 41, 51, 46, 46, 42, 39, 49	0.168 Liters	Standard Error 0.0291
UMEC 31.25 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	15 min, n=41, 41, 51, 46, 46, 42, 39, 49	0.108 Liters	Standard Error 0.0294
UMEC 31.25 µg BID	Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period	12 h, n=41, 41, 51, 46, 46, 41, 39, 49	0.056 Liters	Standard Error 0.036

Source: ClinicalTrials.gov · Data processed: Mar 17, 2026

A 3-period Crossover Study With GSK573719 as Monotherapy in Adult Subjects With Asthma

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Change From Baseline in Albumin, Total Protein, and Hemoglobin on Day 14 of Each Treatment Period

Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) on Day 14 of Each Treatment Period

Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (ANC - Absolute Neutrophil Count), Platelet, and Leukocytes Count on Day 14 of Each Treatment Period

Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) on Day 14 of Each Treatment Period

Change From Baseline in Diastolic Blood Pressure on Day 14 of Each Treatment Period

Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine on Day 14 of Each Treatment Period

Change From Baseline in Hematocrit on Day 14 of Each Treatment Period

Change From Baseline in Pulse Rate on Day 14 of Each Treatment Period

Change From Baseline in Systolic Blood Pressure on Day 14 of Each Treatment Period

Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Segmented Neutrophils in Blood on Day 14 of Each Treatment Period

Change From Baseline in Trough FEV1 on Day 15 of Each Treatment Period

Final Dose-response Model for Trough Forced Expiratory Volume in One Second (FEV1)

Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick on Day 14 of Each Treatment Period

Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)

Number of Participants With Asthma Exacerbations During the Treatment Period

Number of Participants With the Indicated 24 Hour Holter Findings

Number of Participants With the Indicated Abnormal Electrocardiogram Findings

Urine pH on Day 14 of Each Treatment Period

Urine Specific Gravity on Day 14 of Each Treatment Period

Change From Baseline (BL) in the Weighted Mean (WM) 0-24 Hour FEV1 Obtained Post-AM Dose on Day 14 of Each Treatment Period

Change From Baseline in Mean Morning (AM) and Evening (PM) Pre-treatment Peak Expiratory Flow (PEF) Over Day 7 to Day 14 of Each Treatment Period

Change From Baseline in the Mean Number of Puffs Per Day of Rescue Albuterol/Salbutamol Over Day 7 to Day 14 of Each Treatment Period

Change in Baseline in Serial FEV1 Over 0-24 Hours After the Morning Dose on Day 14 of Each Treatment Period