Blood samples were collected for the measurement of hematocrit at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Blood samples were collected for the measurement of MCV at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Blood samples were collected for the measurement of MCH at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Blood samples were collected for the measurement of ALT, ALP, AST, and GGT at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Blood samples were collected for the measurement of albumin and total protein at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Blood samples were collected for the measurement of cholesterol, chloride, potassium, sodium, triglycerides, and urea at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Blood samples were collected for the measurement of total bilirubin and creatinine at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Blood samples were collected for the measurement of c-reactive protein at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

SBP and DBP were measured at Baseline and over the post-dose 24 h period at the following scheduled time points: 20 minutes (M), 45 M, 1h, 2h, 3h, 4h, 6h, and 24 h. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Heart rate (HR) was measured at Baseline and over the post-dose 24 h period at the following scheduled time points: 20 minutes (M), 45 M, 1 h, 2 h, 3 h, 4 h, 6 h, and 24 h. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

ECG parameters [PR, QRS, RR, QT (uncorrected), QTcB (QT corrected by Bazett's formula) and QTcF (QT corrected by Fridericia's formula) intervals] were measured at Baseline and over the post-dose 24h period at the following scheduled time points: 20 minutes (min), 45 min, 1 h, 2 h, 3 h, 4 h, 6 h, and 24 h. Baseline was defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the 12-lead ECG. QTcB is the QT interval corrected for heart rate using Bazett's formula; QTcF is the QT interval corrected for heart rate using Fridericia's formula. Weighted mean (WM) is derived by calculating the area under curve (AUC), and then dividing by the relevant time interval. QTcB and QTcF recorded at 20 minutes, 45 minutes, 1, 2, 3, and 4 hours post-dose on Day 1 of each treatment period were used for analysis. The data is presented as the adjusted means of WM and maximum QTc(B) and QTc(F).

Weighted mean (WM) is derived by calculating the area under curve (AUC), and then dividing by the relevant time interval. Heart rate was recorded at Screening, prior to dosing, and at 20 minutes, 45 minutes, 1, 2, 3, 4 and 6 hours post-dose on Day 1of each treatment period. Heart rate recorded at 20 minutes, 45 minutes and 1, 2, 3 and 4 hours post-dose on Day 1of the each treatment period were used for analysis. Heart rate measurement was taken in a supine position having rested in this position for at least 10 minutes before each reading. The data is presented as adjusted mean of WM and maximum heart rate.

Blood pressure (BP) measurement included systolic blood pressure (SBP) and diastolic BP (DBP). Weighted mean (WM) is derived by calculating the area under curve (AUC), and then dividing by the relevant time interval. SBP and DBP were recorded at Screening, prior to dosing, and at 20 minutes, 45 minutes, 1,2, 3, 4 and 6 hours post-dose on Day 1of the each treatment period. SBP and DBP recorded at 20 minutes, 45 minutes and 1, 2, 3 and 4 hours post-dose on Day 1of the each treatment period were used for analysis. Heart rate measurement was taken in a supine position having rested in this position for at least 10 minutes before each reading. The data is presented as adjusted mean of WM and maximum SBP and DBP.

Blood samples were collected for the measurement of potassium and glucose at Screening, prior to dosing, and at 20 minutes, 45 minutes, 1,2, 3 and 4 hours post-dose on Day 1of the each treatment period. Whole blood samples (approximately 1.0 milliliter [mL]) was analysed for potassium and glucose using the i-STAT1 portable chemical analyser. The i-STAT1 system is an analyser designed for point of care testing and employs a hand-held chemistry analyzer and disposable cartridges, which in the configuration tested, are capable of measuring potassium, glucose, blood gases, electrolytes, metabolites and coagulation. Weighted mean (WM) is derived by calculating the area under curve (AUC), and then dividing by the relevant time interval. The data is presented as adjusted mean of WM and maximum (max) glucose /minimum (min) potassium.

Blood samples were collected pre-dose and at 2, 5, 10, 20, and 30 minutes, 1, 2, 4, 6, 8, 10, and 24 hour post-dose. Blood samples were analyzed for GW642444 and its metabolites GI179710, GW630200 and GSK932009 using a high performance liquid chromatography/mass spectrometry/mass (HPLC/MS/MS) spectrometry. AUC defined as area under the plasma concentration curve from time zero to the last quantifiable concentration (AUC(0-t)), and up to 1 hour post-dose (AUC(0-1)) were determined by non-compartmental methods. Assay censoring refers to some of the values being below the limit of quantification such that this parameter could not be defined.

Blood samples were collected pre-dose and at 2, 5, 10, 20, and 30 minutes, 1, 2, 4, 6, 8, 10, and 24 hour post-dose. Blood samples were analyzed for GW642444 and its metabolites GI179710, GW630200 and GSK932009, using a high performance liquid chromatography/mass spectrometry/mass (HPLC/MS/MS) spectrometry. The maximum observed plasma concentration (Cmax) was determined from the concentration time data by non-compartmental methods. Assay censoring refers to some of the values being below the limit of quantification such that this parameter could not be defined.

Blood samples were collected pre-dose and at 2, 5, 10, 20, and 30 minutes, 1, 2, 4, 6, 8, 10, and 24 hour post-dose. Blood samples were analyzed for GW642444 and its metabolites GI179710, GW630200 and GSK932009, using a high performance liquid chromatography/mass spectrometry/mass (HPLC/MS/MS) spectrometry. The Time to maximum plasma concentration (Tmax) was determined from the concentration time data by non-compartmental methods. Assay censoring refers to some of the values being below the limit of quantification such that this parameter could not be defined.

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

Participants received GW642444M 25 µg single dose in the morning from the dry powder inhaler (DPI) from the DISKUS/ACCUHALER (one inhalation in the morning).

Participants received GW642444M 50 µg single dose in the morning from the dry powder inhaler (DPI) from the DISKUS/ACCUHALER (one inhalation in the morning).

Participants received GW642444M 100 µg single dose in the morning from the dry powder inhaler (DPI) from the DISKUS/ACCUHALER (one inhalation in the morning).

Participants received GW642444H 100 µg single dose in the morning from the dry powder inhaler (DPI) from the DISKUS/ACCUHALER (one inhalation in the morning).

Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count, and white blood cell (WBC) count at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

Blood samples were collected for the measurement of hemoglobin and MCHC at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

Blood samples were collected for the measurement of reticulocyte and RBCs at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

Blood samples were collected for the measurement of hematocrit at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

Blood samples were collected for the measurement of MCV at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Blood samples were collected for the measurement of MCV at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Blood samples were collected for the measurement of MCH at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

Blood samples were collected for the measurement of ALT, ALP, AST, and GGT at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

All Subjects Population, Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

Blood samples were collected for the measurement of albumin and total protein at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

Blood samples were collected for the measurement of cholesterol, chloride, potassium, sodium, triglycerides, and urea at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

Blood samples were collected for the measurement of total bilirubin and creatinine at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

Blood samples were collected for the measurement of c-reactive protein at Baseline and 24 hours post-dose on Day 1of each treatment period. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

SBP and DBP were measured at Baseline and over the post-dose 24 h period at the following scheduled time points: 20 minutes (M), 45 M, 1h, 2h, 3h, 4h, 6h, and 24 h. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.

Heart rate (HR) was measured at Baseline and over the post-dose 24 h period at the following scheduled time points: 20 minutes (M), 45 M, 1 h, 2 h, 3 h, 4 h, 6 h, and 24 h. Baseline is defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Per Protocol (PP) Population: all participants included in the All Subjects population excluding a participant deemed not to have heart rate or other ECG parameters deemed suitable for evaluation. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

ECG parameters [PR, QRS, RR, QT (uncorrected), QTcB (QT corrected by Bazett's formula) and QTcF (QT corrected by Fridericia's formula) intervals] were measured at Baseline and over the post-dose 24h period at the following scheduled time points: 20 minutes (min), 45 min, 1 h, 2 h, 3 h, 4 h, 6 h, and 24 h. Baseline was defined as the measurement at Screening (Day -28 to Day -1). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

PP Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the PP Population.

Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured electronically by spirometry. The data is presented as adjusted mean of the FEV1 values over 23 and 24 hours after dosing. Changed in trough FEV1 will be analysed using a model with baseline, treatment, period, as fixed effects .

PP Population. Only those participants available at the indicated time points were assessed.

QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the 12-lead ECG. QTcB is the QT interval corrected for heart rate using Bazett's formula; QTcF is the QT interval corrected for heart rate using Fridericia's formula. Weighted mean (WM) is derived by calculating the area under curve (AUC), and then dividing by the relevant time interval. QTcB and QTcF recorded at 20 minutes, 45 minutes, 1, 2, 3, and 4 hours post-dose on Day 1 of each treatment period were used for analysis. The data is presented as the adjusted means of WM and maximum QTc(B) and QTc(F).

PP Population. Only those participants available at the indicated time points were assessed.

Weighted mean (WM) is derived by calculating the area under curve (AUC), and then dividing by the relevant time interval. Heart rate was recorded at Screening, prior to dosing, and at 20 minutes, 45 minutes, 1, 2, 3, 4 and 6 hours post-dose on Day 1of each treatment period. Heart rate recorded at 20 minutes, 45 minutes and 1, 2, 3 and 4 hours post-dose on Day 1of the each treatment period were used for analysis. Heart rate measurement was taken in a supine position having rested in this position for at least 10 minutes before each reading. The data is presented as adjusted mean of WM and maximum heart rate.

PP Population. Only those participants available at the indicated time points were assessed.

Blood pressure (BP) measurement included systolic blood pressure (SBP) and diastolic BP (DBP). Weighted mean (WM) is derived by calculating the area under curve (AUC), and then dividing by the relevant time interval. SBP and DBP were recorded at Screening, prior to dosing, and at 20 minutes, 45 minutes, 1,2, 3, 4 and 6 hours post-dose on Day 1of the each treatment period. SBP and DBP recorded at 20 minutes, 45 minutes and 1, 2, 3 and 4 hours post-dose on Day 1of the each treatment period were used for analysis. Heart rate measurement was taken in a supine position having rested in this position for at least 10 minutes before each reading. The data is presented as adjusted mean of WM and maximum SBP and DBP.

PP Population. Only those participants available at the indicated time points were assessed.

Blood samples were collected for the measurement of potassium and glucose at Screening, prior to dosing, and at 20 minutes, 45 minutes, 1,2, 3 and 4 hours post-dose on Day 1of the each treatment period. Whole blood samples (approximately 1.0 milliliter [mL]) was analysed for potassium and glucose using the i-STAT1 portable chemical analyser. The i-STAT1 system is an analyser designed for point of care testing and employs a hand-held chemistry analyzer and disposable cartridges, which in the configuration tested, are capable of measuring potassium, glucose, blood gases, electrolytes, metabolites and coagulation. Weighted mean (WM) is derived by calculating the area under curve (AUC), and then dividing by the relevant time interval. The data is presented as adjusted mean of WM and maximum (max) glucose /minimum (min) potassium.

PP Population. Only those participants available at the indicated time points were assessed.

Blood samples were collected pre-dose and at 2, 5, 10, 20, and 30 minutes, 1, 2, 4, 6, 8, 10, and 24 hour post-dose. Blood samples were analyzed for GW642444 and its metabolites GI179710, GW630200 and GSK932009 using a high performance liquid chromatography/mass spectrometry/mass (HPLC/MS/MS) spectrometry. AUC defined as area under the plasma concentration curve from time zero to the last quantifiable concentration (AUC(0-t)), and up to 1 hour post-dose (AUC(0-1)) were determined by non-compartmental methods. Assay censoring refers to some of the values being below the limit of quantification such that this parameter could not be defined.

Pharmacokinetic (PK) Population: all participants who received at least one dose and for whom a PK sample was obtained and analyzed

Blood samples were collected pre-dose and at 2, 5, 10, 20, and 30 minutes, 1, 2, 4, 6, 8, 10, and 24 hour post-dose. Blood samples were analyzed for GW642444 and its metabolites GI179710, GW630200 and GSK932009, using a high performance liquid chromatography/mass spectrometry/mass (HPLC/MS/MS) spectrometry. The maximum observed plasma concentration (Cmax) was determined from the concentration time data by non-compartmental methods. Assay censoring refers to some of the values being below the limit of quantification such that this parameter could not be defined.

PK Population: all participants who received at least one dose and for whom a PK sample was obtained and analyzed

Blood samples were collected pre-dose and at 2, 5, 10, 20, and 30 minutes, 1, 2, 4, 6, 8, 10, and 24 hour post-dose. Blood samples were analyzed for GW642444 and its metabolites GI179710, GW630200 and GSK932009, using a high performance liquid chromatography/mass spectrometry/mass (HPLC/MS/MS) spectrometry. The Time to maximum plasma concentration (Tmax) was determined from the concentration time data by non-compartmental methods. Assay censoring refers to some of the values being below the limit of quantification such that this parameter could not be defined.

PK Population: all participants who received at least one dose and for whom a PK sample was obtained and analyzed

Participants received GW642444M 25 µg single dose in the morning from the dry powder inhaler (DPI) from the DISKUS/ACCUHALER (one inhalation in the morning).

Participants received GW642444M 50 µg single dose in the morning from the dry powder inhaler (DPI) from the DISKUS/ACCUHALER (one inhalation in the morning).

Participants received GW642444M 100 µg single dose in the morning from the dry powder inhaler (DPI) from the DISKUS/ACCUHALER (one inhalation in the morning).

Participants received GW642444H 100 µg single dose in the morning from the dry powder inhaler (DPI) from the DISKUS/ACCUHALER (one inhalation in the morning).