Trial Outcomes & Findings for A Dose Ascending, Study To Examine The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of GSK233705B. (NCT NCT00453479)

Last Updated: 2018-03-12

Results Overview

An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

23 participants

Primary outcome timeframe

Up to follow-up (approximately 45 days)

Results posted on

2018-03-12

Participant Flow

From 29 March 2007 to 11 October 2007, total of 23 participants with chronic obstructive pulmonary disease (COPD) were randomized at four centres in the Netherlands. DISKUS™ is registered product of GlaxoSmithKline.

Participant milestones

Participant milestones
Measure	Placebo Participants entered into Cohort I received single inhaled dose of dry powder inhaler (DPI) of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) and was formulated with lactose only as a vehicle to make 12.5 milligrams (mg).	GSK233705 50 µg Twice Daily Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 micrograms (µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Overall Study STARTED	6	9	8
Overall Study COMPLETED	6	9	8
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Dose Ascending, Study To Examine The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of GSK233705B.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=6 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily n=8 Participants Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	Total n=23 Participants Total of all reporting groups
Age, Continuous	60.0 Years STANDARD_DEVIATION 11.15 • n=5 Participants	66.4 Years STANDARD_DEVIATION 6.31 • n=7 Participants	59.0 Years STANDARD_DEVIATION 7.27 • n=5 Participants	62.2 Years STANDARD_DEVIATION 8.48 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	9 Participants n=7 Participants	5 Participants n=5 Participants	19 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	9 Participants n=7 Participants	8 Participants n=5 Participants	23 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to follow-up (approximately 45 days)

Population: All subject population included all available data on participants who had received at least one dose of study medication (including placebo).

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily n=8 Participants Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) Any AE	4 Participants	4 Participants	4 Participants
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) Any SAE	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Day 7 (24 hours post-dose)

Population: All subject population was used.

Blood pressure was measured subsequent to 12 lead electrocardiogram (ECG). Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7.

Outcome measures

PRIMARY outcome

Timeframe: Up to Day 7 (24 hour post dose)

Population: All subject population was used.

Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily n=8 Participants Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Summary of Mean Heart Rate Day 1, 8 hour	65.7 Beats per minute Standard Deviation 5.75	68.1 Beats per minute Standard Deviation 11.12	66.9 Beats per minute Standard Deviation 6.01
Summary of Mean Heart Rate Day 1, 24 hour	62.3 Beats per minute Standard Deviation 10.25	68.1 Beats per minute Standard Deviation 13.13	65.5 Beats per minute Standard Deviation 8.45
Summary of Mean Heart Rate Day 7, 30 minutes	63.3 Beats per minute Standard Deviation 6.25	66.7 Beats per minute Standard Deviation 11.79	65.0 Beats per minute Standard Deviation 7.33
Summary of Mean Heart Rate Day 1, Baseline	65.7 Beats per minute Standard Deviation 7.07	66.7 Beats per minute Standard Deviation 9.68	71.5 Beats per minute Standard Deviation 8.50
Summary of Mean Heart Rate Day 1, 15 minutes	62.2 Beats per minute Standard Deviation 8.06	65.1 Beats per minute Standard Deviation 8.07	70.4 Beats per minute Standard Deviation 10.57
Summary of Mean Heart Rate Day 1, 30 minutes	61.2 Beats per minute Standard Deviation 5.78	64.9 Beats per minute Standard Deviation 8.57	66.6 Beats per minute Standard Deviation 7.42
Summary of Mean Heart Rate Day 1, 1.5 hour	64.7 Beats per minute Standard Deviation 9.52	62.7 Beats per minute Standard Deviation 9.63	64.9 Beats per minute Standard Deviation 6.29
Summary of Mean Heart Rate Day 1, 4 hour	63.2 Beats per minute Standard Deviation 6.31	66.6 Beats per minute Standard Deviation 14.57	64.0 Beats per minute Standard Deviation 8.37
Summary of Mean Heart Rate Day 7, Baseline	63.6 Beats per minute Standard Deviation 4.62	67.0 Beats per minute Standard Deviation 8.20	67.8 Beats per minute Standard Deviation 8.30
Summary of Mean Heart Rate Day 7, 15 minutes	65.3 Beats per minute Standard Deviation 6.56	68.3 Beats per minute Standard Deviation 14.27	64.5 Beats per minute Standard Deviation 6.55
Summary of Mean Heart Rate Day 7, 1.5 hour	60.0 Beats per minute Standard Deviation 7.01	64.0 Beats per minute Standard Deviation 11.61	62.5 Beats per minute Standard Deviation 8.25
Summary of Mean Heart Rate Day 7, 4 hour	64.3 Beats per minute Standard Deviation 8.91	66.2 Beats per minute Standard Deviation 12.72	63.0 Beats per minute Standard Deviation 8.43
Summary of Mean Heart Rate Day 7, 8 hour	65.3 Beats per minute Standard Deviation 4.89	66.1 Beats per minute Standard Deviation 7.62	66.3 Beats per minute Standard Deviation 5.47
Summary of Mean Heart Rate Day 7, 24 hour	68.0 Beats per minute Standard Deviation 9.78	70.2 Beats per minute Standard Deviation 17.22	65.5 Beats per minute Standard Deviation 5.98

PRIMARY outcome

Timeframe: Up to Day 7 (0-4 hour)

Population: All subject population

Blood pressure was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily n=8 Participants Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose SBP, Day 1	132.52 Millimeters of mercury Interval 123.46 to 141.58	131.56 Millimeters of mercury Interval 124.15 to 138.97	138.73 Millimeters of mercury Interval 130.88 to 146.59
Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose SBP, Day 7	132.43 Millimeters of mercury Interval 125.61 to 139.26	128.33 Millimeters of mercury Interval 122.75 to 133.92	127.67 Millimeters of mercury Interval 121.76 to 133.59
Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose DBP, Day 1	81.21 Millimeters of mercury Interval 77.72 to 84.71	81.80 Millimeters of mercury Interval 79.0 to 84.6	82.19 Millimeters of mercury Interval 79.17 to 85.22
Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose DBP, Day 7	86.14 Millimeters of mercury Interval 82.24 to 90.03	79.50 Millimeters of mercury Interval 76.38 to 82.62	75.33 Millimeters of mercury Interval 71.96 to 78.7

PRIMARY outcome

Timeframe: Up to Day 7 (0-4 hour)

Population: All subject population was used.

Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily n=8 Participants Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Maximum Value of Heart Rate (0-4 Hour) for the Morning Dose Day 1	68.32 Beats per minute Interval 62.19 to 74.46	70.58 Beats per minute Interval 65.6 to 75.57	68.48 Beats per minute Interval 63.07 to 73.89
Maximum Value of Heart Rate (0-4 Hour) for the Morning Dose Day 7	69.30 Beats per minute Interval 63.1 to 75.5	71.92 Beats per minute Interval 66.89 to 76.96	63.86 Beats per minute Interval 58.39 to 69.33

PRIMARY outcome

Timeframe: Up to Day 7 (0-4 hour)

Population: All subject population was used.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily n=8 Participants Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose DBP, Day 7	81.37 Millimeters of mercury Interval 77.91 to 84.84	77.49 Millimeters of mercury Interval 74.71 to 80.26	71.99 Millimeters of mercury Interval 68.99 to 74.98
Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose SBP, Day 1	128.31 Millimeters of mercury Interval 120.84 to 135.77	125.53 Millimeters of mercury Interval 119.43 to 131.64	131.32 Millimeters of mercury Interval 124.85 to 137.79
Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose SBP, Day 7	125.87 Millimeters of mercury Interval 119.53 to 132.21	123.99 Millimeters of mercury Interval 118.81 to 129.17	122.37 Millimeters of mercury Interval 116.88 to 127.87
Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose DBP, Day 1	78.22 Millimeters of mercury Interval 75.24 to 81.2	77.94 Millimeters of mercury Interval 75.56 to 80.33	76.47 Millimeters of mercury Interval 73.89 to 79.04

PRIMARY outcome

Timeframe: Up to Day 7 (0-4 hour)

Population: All subject population was used.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily n=8 Participants Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Weighted Mean of Heart Rate (0-4 Hour) for the Morning Dose Day 1	65.46 Beats per minute Interval 61.04 to 69.88	65.60 Beats per minute Interval 62.0 to 69.19	62.79 Beats per minute Interval 58.89 to 66.7
Weighted Mean of Heart Rate (0-4 Hour) for the Morning Dose Day 7	64.31 Beats per minute Interval 59.7 to 68.92	66.70 Beats per minute Interval 62.96 to 70.44	60.47 Beats per minute Interval 56.4 to 64.53

PRIMARY outcome

Timeframe: Up to Day 7 (24 hour post dose)

Population: All subject population was used. Only those participants available at the specified time points were analyzed.

Single measurements were taken at all time points. The pre-dose values were classed as Baseline. Data for number of participants with normal, abnormal not clinically significant and abnormal clinically significant is presented. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily n=8 Participants Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Number of Participants With Abnormal 12-lead ECG Findings Day 1, Baseline · Abnormal not clinically significant	3 Participants	4 Participants	2 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, Baseline · Abnormal clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, 4 hour · Abnormal not clinically significant	4 Participants	6 Participants	3 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, 24 hour · Abnormal clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, Baseline · Abnormal not clinically significant	3 Participants	4 Participants	2 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, 15 minutes · Normal	2 Participants	4 Participants	6 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, 4 hour · Abnormal not clinically significant	4 Participants	4 Participants	2 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, Baseline · Normal	3 Participants	5 Participants	6 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, 15 minutes · Normal	2 Participants	4 Participants	5 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, 15 minutes · Abnormal not clinically significant	4 Participants	5 Participants	3 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, 15 minutes · Abnormal clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, 30 minutes · Normal	3 Participants	5 Participants	5 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, 30 minutes · Abnormal not clinically significant	3 Participants	4 Participants	3 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, 30 minutes · Abnormal clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, 1.5 hour · Normal	3 Participants	7 Participants	3 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, 1.5 hour · Abnormal not clinically significant	3 Participants	2 Participants	5 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, 1.5 hour · Abnormal clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, 4 hour · Normal	2 Participants	3 Participants	5 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, 4 hour · Abnormal clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, 8 hour · Normal	3 Participants	5 Participants	5 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, 8 hour · Abnormal not clinically significant	3 Participants	4 Participants	3 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, 8 hour · Abnormal clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, 24 hour · Normal	3 Participants	5 Participants	5 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 1, 24 hour · Abnormal not clinically significant	3 Participants	4 Participants	3 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, Baseline · Normal	3 Participants	5 Participants	6 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, Baseline · Abnormal clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, 15 minutes · Abnormal not clinically significant	4 Participants	5 Participants	2 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, 15 minutes · Abnormal clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, 30 minutes · Normal	2 Participants	5 Participants	6 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, 30 minutes · Abnormal not clinically significant	4 Participants	4 Participants	2 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, 30 minutes · Abnormal clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, 1.5 hour · Normal	2 Participants	3 Participants	6 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, 1.5 hour · Abnormal not clinically significant	4 Participants	6 Participants	2 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, 1.5 hour · Abnormal clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, 4 hour · Normal	1 Participants	5 Participants	6 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, 4 hour · Abnormal clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, 8 hour · Normal	3 Participants	5 Participants	6 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, 8 hour · Abnormal not clinically significant	3 Participants	4 Participants	2 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, 8 hour · Abnormal clinically significant	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, 24 hour · Normal	2 Participants	4 Participants	6 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, 24 hour · Abnormal not clinically significant	4 Participants	5 Participants	2 Participants
Number of Participants With Abnormal 12-lead ECG Findings Day 7, 24 hour · Abnormal clinically significant	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Day 7 (0-4 hour)

Population: All subject population was used.

Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily n=8 Participants Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B) QTcB, Day 1	406.29 Milliseconds Interval 392.99 to 419.6	410.71 Milliseconds Interval 399.93 to 421.48	416.86 Milliseconds Interval 405.3 to 428.42
Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B) QTcB, Day 7	400.21 Milliseconds Interval 389.18 to 411.23	409.23 Milliseconds Interval 400.3 to 418.16	416.71 Milliseconds Interval 407.13 to 426.29
Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B) QTcF, Day 1	402.97 Milliseconds Interval 388.5 to 417.43	405.10 Milliseconds Interval 393.37 to 416.83	420.63 Milliseconds Interval 408.14 to 433.11
Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B) QTcF, Day 7	395.77 Milliseconds Interval 387.16 to 404.37	408.06 Milliseconds Interval 401.08 to 415.04	418.08 Milliseconds Interval 410.66 to 425.51

PRIMARY outcome

Timeframe: Up to Day 7 (0-4 hour)

Population: All subject population was used.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily n=8 Participants Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B QTcB, Day 1	393.77 Milliseconds Interval 385.19 to 402.36	403.33 Milliseconds Interval 396.38 to 410.28	405.25 Milliseconds Interval 397.79 to 412.71
Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B QTcB, Day 7	392.54 Milliseconds Interval 382.92 to 402.17	400.93 Milliseconds Interval 393.14 to 408.73	407.83 Milliseconds Interval 399.46 to 416.19
Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B QTcF, Day 1	391.25 Milliseconds Interval 383.74 to 398.75	399.57 Milliseconds Interval 393.48 to 405.66	408.08 Milliseconds Interval 401.6 to 414.56
Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B QTcF, Day 7	390.72 Milliseconds Interval 382.21 to 399.22	399.47 Milliseconds Interval 392.57 to 406.37	411.18 Milliseconds Interval 403.83 to 418.52

PRIMARY outcome

Timeframe: Up to Day 7 (24-hour post dose)

Population: All subject population was used.

It was assessed on 1, 2, 4, 9, 12 and 24 hours on Days 1 and 7. Also on Day 7, it was measured on 0 hour (Baseline). At all time points 3 measurements were taken and formal statistical analysis was carried out on the derived maximum readings. Data for adjusted mean is presented as least square mean.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily n=8 Participants Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FEV1, Day 1, 9 hour	1.614 Liters Interval 1.43 to 1.798	1.764 Liters Interval 1.62 to 1.908	1.934 Liters Interval 1.778 to 2.09
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FVC, Day 7, 9 hour	3.449 Liters Interval 3.037 to 3.86	3.714 Liters Interval 3.381 to 4.048	3.894 Liters Interval 3.537 to 4.25
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FVC, Day 7, 12 hour	3.316 Liters Interval 2.868 to 3.765	3.683 Liters Interval 3.32 to 4.046	3.600 Liters Interval 3.212 to 3.989
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FVC, Day 7, 24 hour	3.449 Liters Interval 3.04 to 3.857	3.691 Liters Interval 3.36 to 4.022	3.832 Liters Interval 3.478 to 4.187
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FEV1, Day 1, 24 hour	1.644 Liters Interval 1.456 to 1.832	1.807 Liters Interval 1.66 to 1.955	1.798 Liters Interval 1.638 to 1.957
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FEV1, Day 7, Baseline	1.515 Liters Interval 1.352 to 1.678	1.751 Liters Interval 1.623 to 1.879	1.771 Liters Interval 1.633 to 1.909
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FEV1, Day 7, 1 hour	1.560 Liters Interval 1.361 to 1.759	1.789 Liters Interval 1.633 to 1.945	1.856 Liters Interval 1.687 to 2.025
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FEV1, Day 7, 2 hour	1.665 Liters Interval 1.463 to 1.867	1.760 Liters Interval 1.602 to 1.918	1.867 Liters Interval 1.696 to 2.038
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FEV1, Day 7, 4 hour	1.604 Liters Interval 1.413 to 1.796	1.777 Liters Interval 1.627 to 1.927	1.811 Liters Interval 1.649 to 1.974
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FEV1, Day 7, 9 hour	1.598 Liters Interval 1.367 to 1.83	1.804 Liters Interval 1.623 to 1.985	1.878 Liters Interval 1.682 to 2.074
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FEV1, Day 7, 12 hour	1.526 Liters Interval 1.306 to 1.746	1.746 Liters Interval 1.573 to 1.919	1.719 Liters Interval 1.532 to 1.906
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FEV1, Day 7, 24 hour	1.614 Liters Interval 1.38 to 1.848	1.820 Liters Interval 1.636 to 2.004	1.793 Liters Interval 1.595 to 1.992
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FVC, Day 1, 1 hour	3.623 Liters Interval 3.312 to 3.935	3.761 Liters Interval 3.508 to 4.013	3.776 Liters Interval 3.506 to 4.045
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FVC, Day 1, 2 hour	3.689 Liters Interval 3.387 to 3.99	3.819 Liters Interval 3.575 to 4.063	4.009 Liters Interval 3.748 to 4.271
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FVC, Day 1, 4 hour	3.596 Liters Interval 3.303 to 3.889	3.558 Liters Interval 3.321 to 3.795	3.907 Liters Interval 3.653 to 4.161
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FVC, Day 1, 9 hour	3.571 Liters Interval 3.262 to 3.88	3.631 Liters Interval 3.381 to 3.881	3.919 Liters Interval 3.652 to 4.187
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FVC, Day 1, 12 hour	3.544 Liters Interval 3.188 to 3.9	3.658 Liters Interval 3.37 to 3.947	3.789 Liters Interval 3.48 to 4.097
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FVC, Day 1, 24 hour	3.593 Liters Interval 3.288 to 3.898	3.708 Liters Interval 3.461 to 3.955	3.755 Liters Interval 3.491 to 4.019
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FVC, Day 7, Baseline	3.266 Liters Interval 2.836 to 3.695	3.628 Liters Interval 3.28 to 3.976	3.801 Liters Interval 3.428 to 4.173
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FVC, Day 7, 1 hour	3.375 Liters Interval 2.962 to 3.789	3.644 Liters Interval 3.309 to 3.979	3.999 Liters Interval 3.64 to 4.357
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FVC, Day 7, 2 hour	3.503 Liters Interval 3.097 to 3.909	3.524 Liters Interval 3.195 to 3.853	3.962 Liters Interval 3.61 to 4.314
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FVC, Day 7, 4 hour	3.465 Liters Interval 3.065 to 3.865	3.642 Liters Interval 3.318 to 3.966	3.929 Liters Interval 3.583 to 4.275
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FEV1, Day 1, 1 hour	1.713 Liters Interval 1.571 to 1.855	1.860 Liters Interval 1.749 to 1.971	1.919 Liters Interval 1.799 to 2.039
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FEV1, Day 1, 2 hour	1.726 Liters Interval 1.581 to 1.871	1.897 Liters Interval 1.783 to 2.011	2.055 Liters Interval 1.931 to 2.178
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FEV1, Day 1, 4 hour	1.687 Liters Interval 1.556 to 1.818	1.747 Liters Interval 1.645 to 1.85	1.953 Liters Interval 1.842 to 2.064
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FEV1, Day 1, 12 hour	1.616 Liters Interval 1.445 to 1.786	1.740 Liters Interval 1.607 to 1.874	1.788 Liters Interval 1.643 to 1.932

PRIMARY outcome

Timeframe: Up to Day 7

Population: All subject population was used.

Inhaled salbutamol was used as a rescue medication. Participants were required to keep a diary of their rescue medication (total number of salbutamol doses taken) over the entire 7-day treatment period. Diaries were reviewed by the Investigator when participants were admitted to the unit on Days 1, 2, 7 and 8.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily n=8 Participants Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Number of Participants Who Used Rescue Medication	0 Participants	4 Participants	2 Participants

PRIMARY outcome

Timeframe: Up to Day 7

Population: All subject population was used.

Clinical chemistry parameters included urea, potassium, aspartate aminotransferase (AST), total bilirubin, creatinine, creatine kinase, chloride, alanine aminotransferase (ALT), uric acid, glucose, gamma glutamyltransferase (GGT), albumin, sodium, phosphorus inorganic, calcium, alkaline phosphatase (ALP) and total protein. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours). Data for parameters with above and below the potential clinical concern (PCI) is provided.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily n=8 Participants Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Number of Participants With Abnormalities in Chemistry Data of Clinical Concern Glucose, High	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormalities in Chemistry Data of Clinical Concern Inorganic phosphorus, Low	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormalities in Chemistry Data of Clinical Concern Inorganic phosphorus, High	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to Day 7

Population: All subject population was used.

Hematology parameters included platelet count, red blood cell (RBC) count, mean corpuscular volume (MCV), total neutrophils, white blood cell (WBC) count (absolute), mean corpuscular hemoglobin (MCH), lymphocytes, mean corpuscular hemoglobin concentration (MCHC), monocytes, hemoglobin, eosinophils, hematocrit and basophils. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours). Data for parameters with above and below the PCI is provided.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily n=8 Participants Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Number of Participants With Abnormalities in Hematology Data of Clinical Concern	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Day 7 (pre dose)

Population: All subject population was used.

Urinalysis parameters included protein, blood, ketones, glucose, bilirubin, urobilinogen, leukocyte esterase, specific gravity, nitrites and pH. Sediment microscopy was performed only on urine samples showing an abnormality on the dipstick. Microscopy was performed for: WBC, RBC, hyaline casts, granular casts and cellular casts. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours).

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily n=8 Participants Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results Urine microscopy-RBC-Day 1	1 Participants	0 Participants	0 Participants
Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results Urine microscopy-RBC-Day 7	1 Participants	1 Participants	0 Participants
Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results Urine microscopy-WBC-Day 1	0 Participants	0 Participants	1 Participants
Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results Urine microscopy-WBC-Day 7	1 Participants	1 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to Day 7

Population: All subject population was used.

Holter monitors were switched on immediately prior to dosing (up to 15mins pre-dose) so as to capture Holter ECG data from the 24 hour period following dosing. It was assessed on Day 1 and 7.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily n=8 Participants Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data Maximum heart rate, Day 1	113.35 Beats per minute Interval 108.13 to 118.57	115.58 Beats per minute Interval 111.24 to 119.93	112.08 Beats per minute Interval 107.62 to 116.54
Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data Maximum heart rate, Day 7	114.02 Beats per minute Interval 101.35 to 126.69	119.75 Beats per minute Interval 109.21 to 130.3	115.01 Beats per minute Interval 104.18 to 125.84
Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data Mean heart rate, Day 1	71.260 Beats per minute Interval 65.915 to 76.605	73.994 Beats per minute Interval 69.498 to 78.491	70.186 Beats per minute Interval 65.593 to 74.779
Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data Mean heart rate, Day 7	68.670 Beats per minute Interval 64.101 to 73.238	73.453 Beats per minute Interval 69.61 to 77.295	70.239 Beats per minute Interval 63.313 to 74.164

SECONDARY outcome

Timeframe: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose

Population: PK population was used; this was defined as all participants in the all subjects population for whom a PK sample was obtained and analyzed.

Blood samples were collected at indicated time points. 12 hour pharmacokinetic (PK) sampling was before evening dose.

Outcome measures

SECONDARY outcome

Timeframe: Day 1 and 7 throughout 24 hours

Population: PK population was used.

Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study and consolidated data is presented as 0-12 hours and 12-24 hours. 12 hour pharmacokinetic sampling was before evening dose.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=8 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Urine Concentrations of GSK233705 Day 7, 0-12 hours	316.6091 Nanograms per liter Standard Deviation 80.41509	629.6146 Nanograms per liter Standard Deviation 311.2823	—
Urine Concentrations of GSK233705 Day 7, 12-24 hours	311.6291 Nanograms per liter Standard Deviation 131.1778	643.1492 Nanograms per liter Standard Deviation 218.4276	—
Urine Concentrations of GSK233705 Day 1, 0-12 hours	124.6721 Nanograms per liter Standard Deviation 35.34371	348.9206 Nanograms per liter Standard Deviation 110.1697	—
Urine Concentrations of GSK233705 Day 1, 12-24 hours	179.4939 Nanograms per liter Standard Deviation 47.34615	431.8806 Nanograms per liter Standard Deviation 122.7514	—

SECONDARY outcome

Timeframe: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose

Population: PK population was used.

Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning samples.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=8 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Derived Plasma PK Parameters-area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau) Day 1	0.044 Hour×Nanograms per milliliter Geometric Coefficient of Variation 28.2	0.147 Hour×Nanograms per milliliter Geometric Coefficient of Variation 43.0	—
Derived Plasma PK Parameters-area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau) Day 7	0.189 Hour×Nanograms per milliliter Geometric Coefficient of Variation 39.3	0.430 Hour×Nanograms per milliliter Geometric Coefficient of Variation 44.5	—

SECONDARY outcome

Timeframe: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose

Population: PK population was used.

Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning sample as adjusted geometric mean.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=8 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Derived Plasma PK Parameters-area Under Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-t) Day 7	0.018 Hour×Nanograms per milliliter Interval 0.013 to 0.025	0.056 Hour×Nanograms per milliliter Interval 0.039 to 0.08	—
Derived Plasma PK Parameters-area Under Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-t) Day 1	0.016 Hour×Nanograms per milliliter Interval 0.011 to 0.021	0.053 Hour×Nanograms per milliliter Interval 0.038 to 0.073	—

SECONDARY outcome

Timeframe: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose

Population: PK population was used.

Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning and evening samples as adjusted geometric mean.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=8 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Derived PK Plasma Parameters-area Under Concentration-maximum Observed Plasma Concentration (Cmax) AM Dose, Day 1	0.035 Nanograms per liter Interval 0.025 to 0.05	0.160 Nanograms per liter Interval 0.109 to 0.234	—
Derived PK Plasma Parameters-area Under Concentration-maximum Observed Plasma Concentration (Cmax) AM Dose, Day 7	0.049 Nanograms per liter Interval 0.031 to 0.078	0.190 Nanograms per liter Interval 0.117 to 0.309	—
Derived PK Plasma Parameters-area Under Concentration-maximum Observed Plasma Concentration (Cmax) PM Dose, Day 1	0.052 Nanograms per liter Interval 0.035 to 0.077	0.186 Nanograms per liter Interval 0.123 to 0.281	—
Derived PK Plasma Parameters-area Under Concentration-maximum Observed Plasma Concentration (Cmax) PM Dose, Day 7	0.051 Nanograms per liter Interval 0.032 to 0.08	0.191 Nanograms per liter Interval 0.119 to 0.309	—

SECONDARY outcome

Timeframe: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose

Population: PK population was used.

Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning and evening samples.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=8 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) T-half, Day 1, AM dose	0.624 Hour Interval 0.5 to 1.08	1.167 Hour Interval 0.71 to 2.25	—
Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) T-half, Day 7, AM dose	4.122 Hour Interval 1.66 to 7.01	7.189 Hour Interval 6.59 to 13.97	—
Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) T-last, Day 1, AM dose	1.000 Hour Interval 0.48 to 2.0	2.025 Hour Interval 2.0 to 6.0	—
Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) T-last, Day 7, AM dose	11.920 Hour Interval 2.0 to 12.03	11.920 Hour Interval 11.92 to 12.08	—
Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) T-last, Day 1, PM dose	0.500 Hour Interval 0.25 to 0.5	0.500 Hour Interval 0.48 to 0.52	—
Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) T-last, Day 7, PM dose	0.500 Hour Interval 0.48 to 0.53	0.500 Hour Interval 0.5 to 0.53	—
Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) T-max, Day 1, AM dose	0.080 Hour Interval 0.08 to 1.98	0.080 Hour Interval 0.08 to 0.1	—
Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) T-max, Day 7, AM dose	0.230 Hour Interval 0.08 to 6.0	0.080 Hour Interval 0.08 to 0.1	—
Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) T-max, Day 1, PM dose	0.080 Hour Interval 0.08 to 0.47	0.080 Hour Interval 0.08 to 0.1	—
Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) T-max, Day 7, PM dose	0.080 Hour Interval 0.08 to 0.48	0.080 Hour Interval 0.08 to 0.12	—

SECONDARY outcome

Timeframe: Day 1 and 7 throughout 24 hours

Population: PK population was used.

Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study and consolidated data presented as AM dose and PM dose. 12 hour pharmacokinetic sampling was before evening dose.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=8 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Derived Urine Pharmacokinetic (PK) Parameters-area Under the Plasma Concentration-amount of Drug Excreted Unchanged in Urine (Ae) Ae, Day 1, AM dose	1432.6 Nanogram Geometric Coefficient of Variation 30.6	3977.1 Nanogram Geometric Coefficient of Variation 32.4	—
Derived Urine Pharmacokinetic (PK) Parameters-area Under the Plasma Concentration-amount of Drug Excreted Unchanged in Urine (Ae) Ae, Day 7, AM dose	3661.2 Nanogram Geometric Coefficient of Variation 27.4	6538.3 Nanogram Geometric Coefficient of Variation 66.5	—
Derived Urine Pharmacokinetic (PK) Parameters-area Under the Plasma Concentration-amount of Drug Excreted Unchanged in Urine (Ae) Ae, Day 1, PM dose	2080.2 Nanogram Geometric Coefficient of Variation 29.5	4913.3 Nanogram Geometric Coefficient of Variation 39.0	—
Derived Urine Pharmacokinetic (PK) Parameters-area Under the Plasma Concentration-amount of Drug Excreted Unchanged in Urine (Ae) Ae, Day 7, PM dose	3344.7 Nanogram Geometric Coefficient of Variation 62.0	7328.5 Nanogram Geometric Coefficient of Variation 36.6	—

SECONDARY outcome

Timeframe: Day 1 and 7 throughout 24 hours

Population: PK population was used.

Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study and consolidated data presented as 0-12 hours and 12-24 hours. 12 hour pharmacokinetic sampling was before evening dose.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=8 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Derived Urine PK Parameters-area Under Concentration-fraction of Dose Excreted Unchanged in Urine (Fe) Day 7, PM dose	7.5 Percentage of dose Standard Deviation 3.15	7.7 Percentage of dose Standard Deviation 2.66	—
Derived Urine PK Parameters-area Under Concentration-fraction of Dose Excreted Unchanged in Urine (Fe) Day 1, AM dose	3.0 Percentage of dose Standard Deviation 0.84	4.2 Percentage of dose Standard Deviation 1.30	—
Derived Urine PK Parameters-area Under Concentration-fraction of Dose Excreted Unchanged in Urine (Fe) Day 7, AM dose	7.5 Percentage of dose Standard Deviation 1.88	7.5 Percentage of dose Standard Deviation 3.67	—
Derived Urine PK Parameters-area Under Concentration-fraction of Dose Excreted Unchanged in Urine (Fe) Day 1, PM dose	4.3 Percentage of dose Standard Deviation 1.14	5.2 Percentage of dose Standard Deviation 1.48	—

SECONDARY outcome

Timeframe: Day 1 and 7 throughout 24 hours

Population: PK population was used. Only those participants available at the specified time points were analyzed.

Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study. 12 hour pharmacokinetic sampling was before evening dose.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=8 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Derived Urine PK Parameters-area Under Concentration-renal Clearance (Clr) Day 1	36.2 Liters per hour Geometric Coefficient of Variation 24.5	27.5 Liters per hour Geometric Coefficient of Variation 50.2	—
Derived Urine PK Parameters-area Under Concentration-renal Clearance (Clr) Day 7	19.4 Liters per hour Geometric Coefficient of Variation 49.1	15.2 Liters per hour Geometric Coefficient of Variation 68.4	—

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

GSK233705 50 µg Twice Daily

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

GSK233705 100 µg Twice Daily

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

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

Restriction type: OTHER

Measure	Placebo n=6 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily n=8 Participants Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Day 7, 1.5 hour	127.0 Millimeters of mercury Standard Deviation 16.12	122.8 Millimeters of mercury Standard Deviation 12.55	123.9 Millimeters of mercury Standard Deviation 10.86
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Day 7, 8 hour	131.0 Millimeters of mercury Standard Deviation 20.71	123.3 Millimeters of mercury Standard Deviation 12.59	123.1 Millimeters of mercury Standard Deviation 13.22
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Day 7, 24 hour	130.3 Millimeters of mercury Standard Deviation 15.96	126.6 Millimeters of mercury Standard Deviation 11.67	129.1 Millimeters of mercury Standard Deviation 10.64
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Day 1, 30 minutes	76.2 Millimeters of mercury Standard Deviation 8.80	77.0 Millimeters of mercury Standard Deviation 5.00	77.3 Millimeters of mercury Standard Deviation 10.61
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Day 1, 1.5 hour	74.8 Millimeters of mercury Standard Deviation 6.82	76.2 Millimeters of mercury Standard Deviation 4.02	78.4 Millimeters of mercury Standard Deviation 8.35
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Day 7, 30 minutes	78.8 Millimeters of mercury Standard Deviation 10.70	77.7 Millimeters of mercury Standard Deviation 4.58	74.9 Millimeters of mercury Standard Deviation 11.13
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Day 1, Baseline	129.2 Millimeters of mercury Standard Deviation 15.37	127.7 Millimeters of mercury Standard Deviation 9.03	129.6 Millimeters of mercury Standard Deviation 11.78
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Day 1, 15 minutes	130.0 Millimeters of mercury Standard Deviation 12.84	130.0 Millimeters of mercury Standard Deviation 8.99	130.6 Millimeters of mercury Standard Deviation 16.04
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Day 1, 30 minutes	126.0 Millimeters of mercury Standard Deviation 14.24	123.7 Millimeters of mercury Standard Deviation 10.85	128.4 Millimeters of mercury Standard Deviation 9.32
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Day 1, 1.5 hour	131.2 Millimeters of mercury Standard Deviation 16.17	124.1 Millimeters of mercury Standard Deviation 13.01	133.5 Millimeters of mercury Standard Deviation 18.47
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Day 1, 4 hour	126.2 Millimeters of mercury Standard Deviation 17.52	124.8 Millimeters of mercury Standard Deviation 9.90	132.1 Millimeters of mercury Standard Deviation 12.96
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Day 1, 8 hour	132.8 Millimeters of mercury Standard Deviation 14.26	121.1 Millimeters of mercury Standard Deviation 9.44	124.0 Millimeters of mercury Standard Deviation 13.03
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Day 1, 24 hour	131.5 Millimeters of mercury Standard Deviation 13.49	123.1 Millimeters of mercury Standard Deviation 7.64	129.6 Millimeters of mercury Standard Deviation 16.10
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Day 7, Baseline	124.6 Millimeters of mercury Standard Deviation 15.25	122.7 Millimeters of mercury Standard Deviation 11.94	123.9 Millimeters of mercury Standard Deviation 9.21
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Day 7, 15 minutes	127.5 Millimeters of mercury Standard Deviation 16.43	123.1 Millimeters of mercury Standard Deviation 12.75	123.6 Millimeters of mercury Standard Deviation 11.13
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Day 7, 30 minutes	122.5 Millimeters of mercury Standard Deviation 22.21	124.6 Millimeters of mercury Standard Deviation 13.41	119.5 Millimeters of mercury Standard Deviation 9.58
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Day 7, 4 hour	127.2 Millimeters of mercury Standard Deviation 13.26	122.7 Millimeters of mercury Standard Deviation 10.78	123.9 Millimeters of mercury Standard Deviation 15.42
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Day 1, Baseline	74.7 Millimeters of mercury Standard Deviation 8.69	77.4 Millimeters of mercury Standard Deviation 4.29	80.0 Millimeters of mercury Standard Deviation 10.60
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Day 1, 15 minutes	78.0 Millimeters of mercury Standard Deviation 7.43	78.9 Millimeters of mercury Standard Deviation 4.11	81.1 Millimeters of mercury Standard Deviation 9.95
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Day 1, 4 hour	77.3 Millimeters of mercury Standard Deviation 9.42	80.3 Millimeters of mercury Standard Deviation 5.32	77.9 Millimeters of mercury Standard Deviation 12.08
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Day 1, 8 hour	75.3 Millimeters of mercury Standard Deviation 9.16	75.7 Millimeters of mercury Standard Deviation 5.41	72.6 Millimeters of mercury Standard Deviation 10.95
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Day 1, 24 hour	77.2 Millimeters of mercury Standard Deviation 6.05	77.4 Millimeters of mercury Standard Deviation 3.32	76.0 Millimeters of mercury Standard Deviation 12.98
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Day 7, Baseline	77.0 Millimeters of mercury Standard Deviation 8.80	76.7 Millimeters of mercury Standard Deviation 5.15	75.4 Millimeters of mercury Standard Deviation 7.21
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Day 7, 15 minutes	82.5 Millimeters of mercury Standard Deviation 10.97	76.1 Millimeters of mercury Standard Deviation 4.65	75.0 Millimeters of mercury Standard Deviation 9.97
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Day 7, 1.5 hour	78.2 Millimeters of mercury Standard Deviation 10.57	76.8 Millimeters of mercury Standard Deviation 4.27	73.6 Millimeters of mercury Standard Deviation 8.99
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Day 7, 4 hour	79.3 Millimeters of mercury Standard Deviation 7.69	78.2 Millimeters of mercury Standard Deviation 4.55	74.0 Millimeters of mercury Standard Deviation 12.72
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Day 7, 8 hour	79.0 Millimeters of mercury Standard Deviation 12.66	75.6 Millimeters of mercury Standard Deviation 5.15	73.4 Millimeters of mercury Standard Deviation 8.33
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Day 7, 24 hour	78.8 Millimeters of mercury Standard Deviation 9.39	77.4 Millimeters of mercury Standard Deviation 4.61	73.4 Millimeters of mercury Standard Deviation 11.50

Measure	Placebo n=9 Participants Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg.	GSK233705 50 µg Twice Daily n=8 Participants Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.	GSK233705 100 µg Twice Daily Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg.
Plasma Concentrations of GSK233705 Day 7, AM dose, 6 hour	0.015 Nanograms per milliliter Standard Deviation 0.0081	0.028 Nanograms per milliliter Standard Deviation 0.0085	—
Plasma Concentrations of GSK233705 Day 7, AM dose, 12 hour	NA Nanograms per milliliter Standard Deviation NA NA indicates data not quantifiable.	0.028 Nanograms per milliliter Standard Deviation 0.0242	—
Plasma Concentrations of GSK233705 Day 1, AM dose, pre-dose	NA Nanograms per milliliter Standard Deviation NA NA indicates data not quantifiable.	NA Nanograms per milliliter Standard Deviation NA NA indicates data not quantifiable.	—
Plasma Concentrations of GSK233705 Day 1, AM dose, 5 minutes	0.039 Nanograms per milliliter Standard Deviation 0.0332	0.181 Nanograms per milliliter Standard Deviation 0.0948	—
Plasma Concentrations of GSK233705 Day 1, AM dose, 15 minutes	0.028 Nanograms per milliliter Standard Deviation 0.0128	0.090 Nanograms per milliliter Standard Deviation 0.0331	—
Plasma Concentrations of GSK233705 Day 1, AM dose, 1 hour	0.012 Nanograms per milliliter Standard Deviation NA NA indicates data not quantifiable.	0.034 Nanograms per milliliter Standard Deviation 0.0115	—
Plasma Concentrations of GSK233705 Day 1, AM dose, 6 hour	NA Nanograms per milliliter Standard Deviation NA NA indicates data not quantifiable.	NA Nanograms per milliliter Standard Deviation NA NA indicates data not quantifiable.	—
Plasma Concentrations of GSK233705 Day 1, AM dose, 12 hour	NA Nanograms per milliliter Standard Deviation NA NA indicates data not quantifiable.	NA Nanograms per milliliter Standard Deviation NA NA indicates data not quantifiable.	—
Plasma Concentrations of GSK233705 Day 1, PM dose, 5 minutes	0.070 Nanograms per milliliter Standard Deviation 0.0327	0.209 Nanograms per milliliter Standard Deviation 0.1066	—
Plasma Concentrations of GSK233705 Day 1, PM dose, 30 minutes	0.024 Nanograms per milliliter Standard Deviation 0.0087	0.062 Nanograms per milliliter Standard Deviation 0.0120	—
Plasma Concentrations of GSK233705 Day 7, AM dose, pre-dose	0.013 Nanograms per milliliter Standard Deviation 0.0111	0.024 Nanograms per milliliter Standard Deviation 0.0070	—
Plasma Concentrations of GSK233705 Day 7, AM dose, 5 minutes	0.062 Nanograms per milliliter Standard Deviation 0.0513	0.226 Nanograms per milliliter Standard Deviation 0.1257	—
Plasma Concentrations of GSK233705 Day 7, AM dose, 15 minutes	0.046 Nanograms per milliliter Standard Deviation 0.0291	0.146 Nanograms per milliliter Standard Deviation 0.0724	—
Plasma Concentrations of GSK233705 Day 7, AM dose, 1 hour	0.025 Nanograms per milliliter Standard Deviation 0.0119	0.061 Nanograms per milliliter Standard Deviation 0.0210	—
Plasma Concentrations of GSK233705 Day 7, PM dose, 5 minutes	0.068 Nanograms per milliliter Standard Deviation 0.0477	0.218 Nanograms per milliliter Standard Deviation 0.1091	—
Plasma Concentrations of GSK233705 Day 7, PM dose, 30 minutes	0.028 Nanograms per milliliter Standard Deviation 0.0115	0.064 Nanograms per milliliter Standard Deviation 0.0233	—