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

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ClinicalTrials.gov Identifier: NCT00453479
Recruitment Status : Completed
First Posted : March 29, 2007
Results First Posted : February 8, 2018
Last Update Posted : March 12, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Primary Purpose: Diagnostic
Condition Pulmonary Disease, Chronic Obstructive
Intervention Drug: GSK233705B
Enrollment 23
Recruitment Details 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.
Pre-assignment Details  
Arm/Group Title Placebo GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description 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). 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. 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.
Period Title: Overall Study
Started 6 9 8
Completed 6 9 8
Not Completed 0 0 0
Arm/Group Title Placebo GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily Total
Hide Arm/Group Description 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. 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. 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 of all reporting groups
Overall Number of Baseline Participants 6 9 8 23
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 9 participants 8 participants 23 participants
60.0  (11.15) 66.4  (6.31) 59.0  (7.27) 62.2  (8.48)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 9 participants 8 participants 23 participants
Female
1
  16.7%
0
   0.0%
3
  37.5%
4
  17.4%
Male
5
  83.3%
9
 100.0%
5
  62.5%
19
  82.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 9 participants 8 participants 23 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
6
 100.0%
9
 100.0%
8
 100.0%
23
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Hide Description 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.
Time Frame Up to follow-up (approximately 45 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject population included all available data on participants who had received at least one dose of study medication (including placebo).
Arm/Group Title Placebo GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 6 9 8
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
4
  66.7%
4
  44.4%
4
  50.0%
Any SAE
0
   0.0%
0
   0.0%
0
   0.0%
2.Primary Outcome
Title Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Hide Description 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.
Time Frame Up to Day 7 (24 hours post-dose)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject population was used.
Arm/Group Title Placebo GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 6 9 8
Mean (Standard Deviation)
Unit of Measure: Millimeters of mercury
SBP, Day 1, Baseline 129.2  (15.37) 127.7  (9.03) 129.6  (11.78)
SBP, Day 1, 15 minutes 130.0  (12.84) 130.0  (8.99) 130.6  (16.04)
SBP, Day 1, 30 minutes 126.0  (14.24) 123.7  (10.85) 128.4  (9.32)
SBP, Day 1, 1.5 hour 131.2  (16.17) 124.1  (13.01) 133.5  (18.47)
SBP, Day 1, 4 hour 126.2  (17.52) 124.8  (9.90) 132.1  (12.96)
SBP, Day 1, 8 hour 132.8  (14.26) 121.1  (9.44) 124.0  (13.03)
SBP, Day 1, 24 hour 131.5  (13.49) 123.1  (7.64) 129.6  (16.10)
SBP, Day 7, Baseline 124.6  (15.25) 122.7  (11.94) 123.9  (9.21)
SBP, Day 7, 15 minutes 127.5  (16.43) 123.1  (12.75) 123.6  (11.13)
SBP, Day 7, 30 minutes 122.5  (22.21) 124.6  (13.41) 119.5  (9.58)
SBP, Day 7, 1.5 hour 127.0  (16.12) 122.8  (12.55) 123.9  (10.86)
SBP, Day 7, 4 hour 127.2  (13.26) 122.7  (10.78) 123.9  (15.42)
SBP, Day 7, 8 hour 131.0  (20.71) 123.3  (12.59) 123.1  (13.22)
SBP, Day 7, 24 hour 130.3  (15.96) 126.6  (11.67) 129.1  (10.64)
DBP, Day 1, Baseline 74.7  (8.69) 77.4  (4.29) 80.0  (10.60)
DBP, Day 1, 15 minutes 78.0  (7.43) 78.9  (4.11) 81.1  (9.95)
DBP, Day 1, 30 minutes 76.2  (8.80) 77.0  (5.00) 77.3  (10.61)
DBP, Day 1, 1.5 hour 74.8  (6.82) 76.2  (4.02) 78.4  (8.35)
DBP, Day 1, 4 hour 77.3  (9.42) 80.3  (5.32) 77.9  (12.08)
DBP, Day 1, 8 hour 75.3  (9.16) 75.7  (5.41) 72.6  (10.95)
DBP, Day 1, 24 hour 77.2  (6.05) 77.4  (3.32) 76.0  (12.98)
DBP, Day 7, Baseline 77.0  (8.80) 76.7  (5.15) 75.4  (7.21)
DBP, Day 7, 15 minutes 82.5  (10.97) 76.1  (4.65) 75.0  (9.97)
DBP, Day 7, 30 minutes 78.8  (10.70) 77.7  (4.58) 74.9  (11.13)
DBP, Day 7, 1.5 hour 78.2  (10.57) 76.8  (4.27) 73.6  (8.99)
DBP, Day 7, 4 hour 79.3  (7.69) 78.2  (4.55) 74.0  (12.72)
DBP, Day 7, 8 hour 79.0  (12.66) 75.6  (5.15) 73.4  (8.33)
DBP, Day 7, 24 hour 78.8  (9.39) 77.4  (4.61) 73.4  (11.50)
3.Primary Outcome
Title Summary of Mean Heart Rate
Hide Description 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.
Time Frame Up to Day 7 (24 hour post dose)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject population was used.
Arm/Group Title Placebo GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 6 9 8
Mean (Standard Deviation)
Unit of Measure: Beats per minute
Day 1, Baseline 65.7  (7.07) 66.7  (9.68) 71.5  (8.50)
Day 1, 15 minutes 62.2  (8.06) 65.1  (8.07) 70.4  (10.57)
Day 1, 30 minutes 61.2  (5.78) 64.9  (8.57) 66.6  (7.42)
Day 1, 1.5 hour 64.7  (9.52) 62.7  (9.63) 64.9  (6.29)
Day 1, 4 hour 63.2  (6.31) 66.6  (14.57) 64.0  (8.37)
Day 1, 8 hour 65.7  (5.75) 68.1  (11.12) 66.9  (6.01)
Day 1, 24 hour 62.3  (10.25) 68.1  (13.13) 65.5  (8.45)
Day 7, Baseline 63.6  (4.62) 67.0  (8.20) 67.8  (8.30)
Day 7, 15 minutes 65.3  (6.56) 68.3  (14.27) 64.5  (6.55)
Day 7, 30 minutes 63.3  (6.25) 66.7  (11.79) 65.0  (7.33)
Day 7, 1.5 hour 60.0  (7.01) 64.0  (11.61) 62.5  (8.25)
Day 7, 4 hour 64.3  (8.91) 66.2  (12.72) 63.0  (8.43)
Day 7, 8 hour 65.3  (4.89) 66.1  (7.62) 66.3  (5.47)
Day 7, 24 hour 68.0  (9.78) 70.2  (17.22) 65.5  (5.98)
4.Primary Outcome
Title Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose
Hide Description 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.
Time Frame Up to Day 7 (0-4 hour)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject population
Arm/Group Title Placebo GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 6 9 8
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Millimeters of mercury
SBP, Day 1
132.52
(123.46 to 141.58)
131.56
(124.15 to 138.97)
138.73
(130.88 to 146.59)
SBP, Day 7
132.43
(125.61 to 139.26)
128.33
(122.75 to 133.92)
127.67
(121.76 to 133.59)
DBP, Day 1
81.21
(77.72 to 84.71)
81.80
(79.00 to 84.60)
82.19
(79.17 to 85.22)
DBP, Day 7
86.14
(82.24 to 90.03)
79.50
(76.38 to 82.62)
75.33
(71.96 to 78.70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.97
Confidence Interval (2-Sided) 95%
-12.68 to 10.75
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.596
Estimation Comments Comparison of SBP Day 1.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.10
Confidence Interval (2-Sided) 95%
-12.92 to 4.72
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.215
Estimation Comments Comparison of SBP Day 7.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 6.21
Confidence Interval (2-Sided) 95%
-5.78 to 18.19
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.727
Estimation Comments Comparison of SBP Day 1.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.76
Confidence Interval (2-Sided) 95%
-13.79 to 4.27
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.314
Estimation Comments Comparison of SBP Day 7.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
-3.89 to 5.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.138
Estimation Comments Comparison of DBP Day 1.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -6.64
Confidence Interval (2-Sided) 95%
-11.62 to -1.65
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.382
Estimation Comments Comparison of DBP Day 7.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
-3.73 to 5.68
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.248
Estimation Comments Comparison of DBP Day 1.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -10.81
Confidence Interval (2-Sided) 95%
-16.05 to -5.57
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.504
Estimation Comments Comparison of DBP Day 7.
5.Primary Outcome
Title Maximum Value of Heart Rate (0-4 Hour) for the Morning Dose
Hide Description 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.
Time Frame Up to Day 7 (0-4 hour)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject population was used.
Arm/Group Title Placebo GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 6 9 8
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Beats per minute
Day 1
68.32
(62.19 to 74.46)
70.58
(65.60 to 75.57)
68.48
(63.07 to 73.89)
Day 7
69.30
(63.10 to 75.50)
71.92
(66.89 to 76.96)
63.86
(58.39 to 69.33)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.26
Confidence Interval (2-Sided) 95%
-5.58 to 10.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.745
Estimation Comments Comparison at Day 1.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.62
Confidence Interval (2-Sided) 95%
-5.30 to 10.54
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.785
Estimation Comments Comparison at Day 7.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
-8.17 to 8.48
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.979
Estimation Comments Comparison at Day 1.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -5.44
Confidence Interval (2-Sided) 95%
-13.86 to 2.97
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.021
Estimation Comments Comparison at Day 7.
6.Primary Outcome
Title Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose
Hide Description 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.
Time Frame Up to Day 7 (0-4 hour)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject population was used.
Arm/Group Title Placebo GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 6 9 8
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Millimeters of mercury
SBP, Day 1
128.31
(120.84 to 135.77)
125.53
(119.43 to 131.64)
131.32
(124.85 to 137.79)
SBP, Day 7
125.87
(119.53 to 132.21)
123.99
(118.81 to 129.17)
122.37
(116.88 to 127.87)
DBP, Day 1
78.22
(75.24 to 81.20)
77.94
(75.56 to 80.33)
76.47
(73.89 to 79.04)
DBP, Day 7
81.37
(77.91 to 84.84)
77.49
(74.71 to 80.26)
71.99
(68.99 to 74.98)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.78
Confidence Interval (2-Sided) 95%
-12.43 to 6.87
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.611
Estimation Comments Comparison of SBP Day 1.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.88
Confidence Interval (2-Sided) 95%
-10.07 to 6.31
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.913
Estimation Comments Comparison of SBP Day 7.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.01
Confidence Interval (2-Sided) 95%
-6.87 to 12.88
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.718
Estimation Comments Comparison of SBP Day 1.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.50
Confidence Interval (2-Sided) 95%
-11.88 to 4.89
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.005
Estimation Comments Comparison of SBP Day 7.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-4.09 to 3.54
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.822
Estimation Comments Comparison of DBP Day 1.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.89
Confidence Interval (2-Sided) 95%
-8.32 to 0.54
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.116
Estimation Comments Comparison of DBP Day 7.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.75
Confidence Interval (2-Sided) 95%
-5.76 to 2.26
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.916
Estimation Comments Comparison of DBP Day 1.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -9.39
Confidence Interval (2-Sided) 95%
-14.04 to -4.73
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.224
Estimation Comments Comparison of DBP Day 7.
7.Primary Outcome
Title Weighted Mean of Heart Rate (0-4 Hour) for the Morning Dose
Hide Description 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.
Time Frame Up to Day 7 (0-4 hour)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject population was used.
Arm/Group Title Placebo GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 6 9 8
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Beats per minute
Day 1
65.46
(61.04 to 69.88)
65.60
(62.00 to 69.19)
62.79
(58.89 to 66.70)
Day 7
64.31
(59.70 to 68.92)
66.70
(62.96 to 70.44)
60.47
(56.40 to 64.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
-5.52 to 5.79
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.700
Estimation Comments Comparison at Day 1.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.39
Confidence Interval (2-Sided) 95%
-3.50 to 8.28
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.813
Estimation Comments Comparison at Day 7.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.67
Confidence Interval (2-Sided) 95%
-8.67 to 3.34
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.869
Estimation Comments Comparison at Day 1.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.84
Confidence Interval (2-Sided) 95%
-10.10 to 2.41
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.989
Estimation Comments Comparison at Day 7.
8.Primary Outcome
Title Number of Participants With Abnormal 12-lead ECG Findings
Hide Description 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.
Time Frame Up to Day 7 (24 hour post dose)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject population was used. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 6 9 8
Measure Type: Count of Participants
Unit of Measure: Participants
Day 1, Baseline Number Analyzed 6 participants 9 participants 8 participants
Normal
3
  50.0%
5
  55.6%
6
  75.0%
Abnormal not clinically significant
3
  50.0%
4
  44.4%
2
  25.0%
Abnormal clinically significant
0
   0.0%
0
   0.0%
0
   0.0%
Day 1, 15 minutes Number Analyzed 6 participants 9 participants 8 participants
Normal
2
  33.3%
4
  44.4%
5
  62.5%
Abnormal not clinically significant
4
  66.7%
5
  55.6%
3
  37.5%
Abnormal clinically significant
0
   0.0%
0
   0.0%
0
   0.0%
Day 1, 30 minutes Number Analyzed 6 participants 9 participants 8 participants
Normal
3
  50.0%
5
  55.6%
5
  62.5%
Abnormal not clinically significant
3
  50.0%
4
  44.4%
3
  37.5%
Abnormal clinically significant
0
   0.0%
0
   0.0%
0
   0.0%
Day 1, 1.5 hour Number Analyzed 6 participants 9 participants 8 participants
Normal
3
  50.0%
7
  77.8%
3
  37.5%
Abnormal not clinically significant
3
  50.0%
2
  22.2%
5
  62.5%
Abnormal clinically significant
0
   0.0%
0
   0.0%
0
   0.0%
Day 1, 4 hour Number Analyzed 6 participants 9 participants 8 participants
Normal
2
  33.3%
3
  33.3%
5
  62.5%
Abnormal not clinically significant
4
  66.7%
6
  66.7%
3
  37.5%
Abnormal clinically significant
0
   0.0%
0
   0.0%
0
   0.0%
Day 1, 8 hour Number Analyzed 6 participants 9 participants 8 participants
Normal
3
  50.0%
5
  55.6%
5
  62.5%
Abnormal not clinically significant
3
  50.0%
4
  44.4%
3
  37.5%
Abnormal clinically significant
0
   0.0%
0
   0.0%
0
   0.0%
Day 1, 24 hour Number Analyzed 6 participants 9 participants 8 participants
Normal
3
  50.0%
5
  55.6%
5
  62.5%
Abnormal not clinically significant
3
  50.0%
4
  44.4%
3
  37.5%
Abnormal clinically significant
0
   0.0%
0
   0.0%
0
   0.0%
Day 7, Baseline Number Analyzed 6 participants 9 participants 8 participants
Normal
3
  50.0%
5
  55.6%
6
  75.0%
Abnormal not clinically significant
3
  50.0%
4
  44.4%
2
  25.0%
Abnormal clinically significant
0
   0.0%
0
   0.0%
0
   0.0%
Day 7, 15 minutes Number Analyzed 6 participants 9 participants 8 participants
Normal
2
  33.3%
4
  44.4%
6
  75.0%
Abnormal not clinically significant
4
  66.7%
5
  55.6%
2
  25.0%
Abnormal clinically significant
0
   0.0%
0
   0.0%
0
   0.0%
Day 7, 30 minutes Number Analyzed 6 participants 9 participants 8 participants
Normal
2
  33.3%
5
  55.6%
6
  75.0%
Abnormal not clinically significant
4
  66.7%
4
  44.4%
2
  25.0%
Abnormal clinically significant
0
   0.0%
0
   0.0%
0
   0.0%
Day 7, 1.5 hour Number Analyzed 6 participants 9 participants 8 participants
Normal
2
  33.3%
3
  33.3%
6
  75.0%
Abnormal not clinically significant
4
  66.7%
6
  66.7%
2
  25.0%
Abnormal clinically significant
0
   0.0%
0
   0.0%
0
   0.0%
Day 7, 4 hour Number Analyzed 5 participants 9 participants 8 participants
Normal
1
  20.0%
5
  55.6%
6
  75.0%
Abnormal not clinically significant
4
  80.0%
4
  44.4%
2
  25.0%
Abnormal clinically significant
0
   0.0%
0
   0.0%
0
   0.0%
Day 7, 8 hour Number Analyzed 6 participants 9 participants 8 participants
Normal
3
  50.0%
5
  55.6%
6
  75.0%
Abnormal not clinically significant
3
  50.0%
4
  44.4%
2
  25.0%
Abnormal clinically significant
0
   0.0%
0
   0.0%
0
   0.0%
Day 7, 24 hour Number Analyzed 6 participants 9 participants 8 participants
Normal
2
  33.3%
4
  44.4%
6
  75.0%
Abnormal not clinically significant
4
  66.7%
5
  55.6%
2
  25.0%
Abnormal clinically significant
0
   0.0%
0
   0.0%
0
   0.0%
9.Primary Outcome
Title 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)
Hide Description 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.
Time Frame Up to Day 7 (0-4 hour)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject population was used.
Arm/Group Title Placebo GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 6 9 8
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Milliseconds
QTcB, Day 1
406.29
(392.99 to 419.60)
410.71
(399.93 to 421.48)
416.86
(405.30 to 428.42)
QTcB, Day 7
400.21
(389.18 to 411.23)
409.23
(400.30 to 418.16)
416.71
(407.13 to 426.29)
QTcF, Day 1
402.97
(388.50 to 417.43)
405.10
(393.37 to 416.83)
420.63
(408.14 to 433.11)
QTcF, Day 7
395.77
(387.16 to 404.37)
408.06
(401.08 to 415.04)
418.08
(410.66 to 425.51)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.42
Confidence Interval (2-Sided) 95%
-12.66 to 21.49
Parameter Dispersion
Type: Standard Error of the Mean
Value: 8.157
Estimation Comments Comparison of QTcB Day 1.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 9.02
Confidence Interval (2-Sided) 95%
-5.13 to 23.17
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.760
Estimation Comments Comparison of QTcB Day 7.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 10.57
Confidence Interval (2-Sided) 95%
-7.24 to 28.38
Parameter Dispersion
Type: Standard Error of the Mean
Value: 8.510
Estimation Comments Comparison of QTcB Day 1.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 16.50
Confidence Interval (2-Sided) 95%
1.74 to 31.26
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.052
Estimation Comments Comparison of QTcB Day 7.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.13
Confidence Interval (2-Sided) 95%
-16.51 to 20.78
Parameter Dispersion
Type: Standard Error of the Mean
Value: 8.908
Estimation Comments Comparison of QTcF Day 1.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 12.29
Confidence Interval (2-Sided) 95%
1.20 to 23.38
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.298
Estimation Comments Comparison of QTcF Day 7.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 17.66
Confidence Interval (2-Sided) 95%
-1.53 to 36.85
Parameter Dispersion
Type: Standard Error of the Mean
Value: 9.171
Estimation Comments Comparison of QTcF Day 1.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 22.32
Confidence Interval (2-Sided) 95%
10.90 to 33.73
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.454
Estimation Comments Comparison of QTcF Day 7.
10.Primary Outcome
Title Weighted Mean (0–4 h) for the Morning Dose of ECG Parameters QTcF and QTc B
Hide Description 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.
Time Frame Up to Day 7 (0-4 hour)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject population was used.
Arm/Group Title Placebo GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 6 9 8
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Milliseconds
QTcB, Day 1
393.77
(385.19 to 402.36)
403.33
(396.38 to 410.28)
405.25
(397.79 to 412.71)
QTcB, Day 7
392.54
(382.92 to 402.17)
400.93
(393.14 to 408.73)
407.83
(399.46 to 416.19)
QTcF, Day 1
391.25
(383.74 to 398.75)
399.57
(393.48 to 405.66)
408.08
(401.60 to 414.56)
QTcF, Day 7
390.72
(382.21 to 399.22)
399.47
(392.57 to 406.37)
411.18
(403.83 to 418.52)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 9.55
Confidence Interval (2-Sided) 95%
-1.46 to 20.57
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.262
Estimation Comments Comparison of QTcB Day 1.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 8.39
Confidence Interval (2-Sided) 95%
-3.97 to 20.74
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.902
Estimation Comments Comparison of QTcB Day 7.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 11.47
Confidence Interval (2-Sided) 95%
-0.02 to 22.96
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.490
Estimation Comments Comparison of QTcB Day 1.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 15.28
Confidence Interval (2-Sided) 95%
2.39 to 28.17
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.157
Estimation Comments Comparison of QTcB Day 7.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 8.32
Confidence Interval (2-Sided) 95%
-1.35 to 18.00
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.622
Estimation Comments Comparison of QTcF Day 1.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 8.75
Confidence Interval (2-Sided) 95%
-2.21 to 19.72
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.239
Estimation Comments Comparison of QTcF Day 7.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 16.83
Confidence Interval (2-Sided) 95%
6.87 to 26.79
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.759
Estimation Comments Comparison of QTcF Day 1.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 20.46
Confidence Interval (2-Sided) 95%
9.17 to 31.75
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.394
Estimation Comments Comparison of QTcF Day 7.
11.Primary Outcome
Title Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC)
Hide Description 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.
Time Frame Up to Day 7 (24-hour post dose)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject population was used.
Arm/Group Title Placebo GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 6 9 8
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Liters
FEV1, Day 1, 1 hour
1.713
(1.571 to 1.855)
1.860
(1.749 to 1.971)
1.919
(1.799 to 2.039)
FEV1, Day 1, 2 hour
1.726
(1.581 to 1.871)
1.897
(1.783 to 2.011)
2.055
(1.931 to 2.178)
FEV1, Day 1, 4 hour
1.687
(1.556 to 1.818)
1.747
(1.645 to 1.850)
1.953
(1.842 to 2.064)
FEV1, Day 1, 9 hour
1.614
(1.430 to 1.798)
1.764
(1.620 to 1.908)
1.934
(1.778 to 2.090)
FEV1, Day 1, 12 hour
1.616
(1.445 to 1.786)
1.740
(1.607 to 1.874)
1.788
(1.643 to 1.932)
FEV1, Day 1, 24 hour
1.644
(1.456 to 1.832)
1.807
(1.660 to 1.955)
1.798
(1.638 to 1.957)
FEV1, Day 7, Baseline
1.515
(1.352 to 1.678)
1.751
(1.623 to 1.879)
1.771
(1.633 to 1.909)
FEV1, Day 7, 1 hour
1.560
(1.361 to 1.759)
1.789
(1.633 to 1.945)
1.856
(1.687 to 2.025)
FEV1, Day 7, 2 hour
1.665
(1.463 to 1.867)
1.760
(1.602 to 1.918)
1.867
(1.696 to 2.038)
FEV1, Day 7, 4 hour
1.604
(1.413 to 1.796)
1.777
(1.627 to 1.927)
1.811
(1.649 to 1.974)
FEV1, Day 7, 9 hour
1.598
(1.367 to 1.830)
1.804
(1.623 to 1.985)
1.878
(1.682 to 2.074)
FEV1, Day 7, 12 hour
1.526
(1.306 to 1.746)
1.746
(1.573 to 1.919)
1.719
(1.532 to 1.906)
FEV1, Day 7, 24 hour
1.614
(1.380 to 1.848)
1.820
(1.636 to 2.004)
1.793
(1.595 to 1.992)
FVC, Day 1, 1 hour
3.623
(3.312 to 3.935)
3.761
(3.508 to 4.013)
3.776
(3.506 to 4.045)
FVC, Day 1, 2 hour
3.689
(3.387 to 3.990)
3.819
(3.575 to 4.063)
4.009
(3.748 to 4.271)
FVC, Day 1, 4 hour
3.596
(3.303 to 3.889)
3.558
(3.321 to 3.795)
3.907
(3.653 to 4.161)
FVC, Day 1, 9 hour
3.571
(3.262 to 3.880)
3.631
(3.381 to 3.881)
3.919
(3.652 to 4.187)
FVC, Day 1, 12 hour
3.544
(3.188 to 3.900)
3.658
(3.370 to 3.947)
3.789
(3.480 to 4.097)
FVC, Day 1, 24 hour
3.593
(3.288 to 3.898)
3.708
(3.461 to 3.955)
3.755
(3.491 to 4.019)
FVC, Day 7, Baseline
3.266
(2.836 to 3.695)
3.628
(3.280 to 3.976)
3.801
(3.428 to 4.173)
FVC, Day 7, 1 hour
3.375
(2.962 to 3.789)
3.644
(3.309 to 3.979)
3.999
(3.640 to 4.357)
FVC, Day 7, 2 hour
3.503
(3.097 to 3.909)
3.524
(3.195 to 3.853)
3.962
(3.610 to 4.314)
FVC, Day 7, 4 hour
3.465
(3.065 to 3.865)
3.642
(3.318 to 3.966)
3.929
(3.583 to 4.275)
FVC, Day 7, 9 hour
3.449
(3.037 to 3.860)
3.714
(3.381 to 4.048)
3.894
(3.537 to 4.250)
FVC, Day 7, 12 hour
3.316
(2.868 to 3.765)
3.683
(3.320 to 4.046)
3.600
(3.212 to 3.989)
FVC, Day 7, 24 hour
3.449
(3.040 to 3.857)
3.691
(3.360 to 4.022)
3.832
(3.478 to 4.187)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.147
Confidence Interval (2-Sided) 95%
-0.035 to 0.328
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0921
Estimation Comments Comparison of FEV1, Day 1, 1 hour
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.171
Confidence Interval (2-Sided) 95%
-0.015 to 0.357
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0944
Estimation Comments Comparison of FEV1, Day 1, 2 hour
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.060
Confidence Interval (2-Sided) 95%
-0.107 to 0.228
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0850
Estimation Comments Comparison of FEV1, Day 1, 4 hour
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.150
Confidence Interval (2-Sided) 95%
-0.085 to 0.386
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1195
Estimation Comments Comparison of FEV1, Day 1, 9 hour
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.124
Confidence Interval (2-Sided) 95%
-0.094 to 0.343
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1107
Estimation Comments Comparison of FEV1, Day 1, 12 hour
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.163
Confidence Interval (2-Sided) 95%
-0.077 to 0.404
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1220
Estimation Comments Comparison of FEV1, Day 1, 24 hour
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.236
Confidence Interval (2-Sided) 95%
0.027 to 0.444
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1057
Estimation Comments Comparison of FEV1, Day 7, Baseline
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.229
Confidence Interval (2-Sided) 95%
-0.026 to 0.483
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1292
Estimation Comments Comparison of FEV1, Day 7, 1 hour
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.095
Confidence Interval (2-Sided) 95%
-0.163 to 0.353
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1309
Estimation Comments Comparison of FEV1, Day 7, 2 hour
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.173
Confidence Interval (2-Sided) 95%
-0.072 to 0.418
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1243
Estimation Comments Comparison of FEV1, Day 7, 4 hour
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.205
Confidence Interval (2-Sided) 95%
-0.090 to 0.501
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1499
Estimation Comments Comparison of FEV1, Day 7, 9 hour
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.220
Confidence Interval (2-Sided) 95%
-0.062 to 0.502
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1430
Estimation Comments Comparison of FEV1, Day 7, 12 hour
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.206
Confidence Interval (2-Sided) 95%
-0.093 to 0.506
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1520
Estimation Comments Comparison of FEV1, Day 7, 24 hour
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.206
Confidence Interval (2-Sided) 95%
0.015 to 0.397
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0970
Estimation Comments Comparison of FEV1, Day 1, 1 hour
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.329
Confidence Interval (2-Sided) 95%
0.133 to 0.525
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0994
Estimation Comments Comparison of FEV1, Day 1, 2 hour
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.266
Confidence Interval (2-Sided) 95%
0.090 to 0.443
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0895
Estimation Comments Comparison of FEV1, Day 1, 4 hour
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.320
Confidence Interval (2-Sided) 95%
0.072 to 0.568
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1258
Estimation Comments Comparison of FEV1, Day 1, 9 hour
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.172
Confidence Interval (2-Sided) 95%
-0.058 to 0.402
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1165
Estimation Comments Comparison of FEV1, Day 1, 12 hour
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.154
Confidence Interval (2-Sided) 95%
-0.099 to 0.407
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1285
Estimation Comments Comparison of FEV1, Day 1, 24 hour
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.256
Confidence Interval (2-Sided) 95%
0.036 to 0.475
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1113
Estimation Comments Comparison of FEV1, Day 7, Baseline
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.296
Confidence Interval (2-Sided) 95%
0.027 to 0.564
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1361
Estimation Comments Comparison of FEV1, Day 7, 1 hour
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.202
Confidence Interval (2-Sided) 95%
-0.069 to 0.474
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1378
Estimation Comments Comparison of FEV1, Day 7, 2 hour
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.207
Confidence Interval (2-Sided) 95%
-0.051 to 0.465
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1309
Estimation Comments Comparison of FEV1, Day 7, 4 hour
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.280
Confidence Interval (2-Sided) 95%
-0.032 to 0.591
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1579
Estimation Comments Comparison of FEV1, Day 7, 9 hour
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.193
Confidence Interval (2-Sided) 95%
-0.104 to 0.490
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1506
Estimation Comments Comparison of FEV1, Day 7, 12 hour
Show Statistical Analysis 26 Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.180
Confidence Interval (2-Sided) 95%
-0.136 to 0.495
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1601
Estimation Comments Comparison of FEV1, Day 7, 24 hour
Show Statistical Analysis 27 Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.137
Confidence Interval (2-Sided) 95%
-0.263 to 0.537
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2029
Estimation Comments Comparison of FVC, Day 1, 1 hour
Show Statistical Analysis 28 Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.131
Confidence Interval (2-Sided) 95%
-0.257 to 0.518
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1965
Estimation Comments Comparison of FVC, Day 1, 2 hour
Show Statistical Analysis 29 Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.038
Confidence Interval (2-Sided) 95%
-0.414 to 0.338
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1908
Estimation Comments Comparison of FVC, Day 1, 4 hour
Show Statistical Analysis 30 Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.060
Confidence Interval (2-Sided) 95%
-0.337 to 0.457
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2013
Estimation Comments Comparison of FVC, Day 1, 9 hour
Show Statistical Analysis 31 Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.115
Confidence Interval (2-Sided) 95%
-0.343 to 0.572
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2322
Estimation Comments Comparison of FVC, Day 1, 12 hour
Show Statistical Analysis 32 Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.115
Confidence Interval (2-Sided) 95%
-0.277 to 0.507
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1988
Estimation Comments Comparison of FVC, Day 1, 24 hour
Show Statistical Analysis 33 Hide Statistical Analysis 33
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.362
Confidence Interval (2-Sided) 95%
-0.190 to 0.914
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2801
Estimation Comments Comparison of FVC, Day 7, Baseline
Show Statistical Analysis 34 Hide Statistical Analysis 34
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.269
Confidence Interval (2-Sided) 95%
-0.263 to 0.800
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2696
Estimation Comments Comparison of FVC, Day 7, 1 hour
Show Statistical Analysis 35 Hide Statistical Analysis 35
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.021
Confidence Interval (2-Sided) 95%
-0.501 to 0.543
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2648
Estimation Comments Comparison of FVC, Day 7, 2 hour
Show Statistical Analysis 36 Hide Statistical Analysis 36
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.177
Confidence Interval (2-Sided) 95%
-0.337 to 0.691
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2606
Estimation Comments Comparison of FVC, Day 7, 4 hour
Show Statistical Analysis 37 Hide Statistical Analysis 37
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.266
Confidence Interval (2-Sided) 95%
-0.263 to 0.795
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2684
Estimation Comments Comparison of FVC, Day 7, 9 hour
Show Statistical Analysis 38 Hide Statistical Analysis 38
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.367
Confidence Interval (2-Sided) 95%
-0.209 to 0.943
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2923
Estimation Comments Comparison of FVC, Day 7, 12 hour
Show Statistical Analysis 39 Hide Statistical Analysis 39
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.242
Confidence Interval (2-Sided) 95%
-0.283 to 0.768
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2665
Estimation Comments Comparison of FVC, Day 7, 24 hour
Show Statistical Analysis 40 Hide Statistical Analysis 40
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.152
Confidence Interval (2-Sided) 95%
-0.263 to 0.567
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2106
Estimation Comments Comparison of FVC, Day 1, 1 hour
Show Statistical Analysis 41 Hide Statistical Analysis 41
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.321
Confidence Interval (2-Sided) 95%
-0.081 to 0.723
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2039
Estimation Comments Comparison of FVC, Day 1, 2 hour
Show Statistical Analysis 42 Hide Statistical Analysis 42
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.311
Confidence Interval (2-Sided) 95%
-0.079 to 0.701
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1981
Estimation Comments Comparison of FVC, Day 1, 4 hour
Show Statistical Analysis 43 Hide Statistical Analysis 43
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.348
Confidence Interval (2-Sided) 95%
-0.064 to 0.760
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2090
Estimation Comments Comparison of FVC, Day 1, 9 hour
Show Statistical Analysis 44 Hide Statistical Analysis 44
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.245
Confidence Interval (2-Sided) 95%
-0.230 to 0.720
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2410
Estimation Comments Comparison of FVC, Day 1, 12 hour
Show Statistical Analysis 45 Hide Statistical Analysis 45
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.162
Confidence Interval (2-Sided) 95%
-0.245 to 0.569
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2063
Estimation Comments Comparison of FVC, Day 1, 24 hour
Show Statistical Analysis 46 Hide Statistical Analysis 46
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.535
Confidence Interval (2-Sided) 95%
-0.038 to 1.108
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2907
Estimation Comments Comparison of FVC, Day 7, Baseline
Show Statistical Analysis 47 Hide Statistical Analysis 47
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.623
Confidence Interval (2-Sided) 95%
0.072 to 1.175
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2798
Estimation Comments Comparison of FVC, Day 7, 1 hour
Show Statistical Analysis 48 Hide Statistical Analysis 48
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.459
Confidence Interval (2-Sided) 95%
-0.083 to 1.000
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2748
Estimation Comments Comparison of FVC, Day 7, 2 hour
Show Statistical Analysis 49 Hide Statistical Analysis 49
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.464
Confidence Interval (2-Sided) 95%
-0.069 to 0.997
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2705
Estimation Comments Comparison of FVC, Day 7, 4 hour
Show Statistical Analysis 50 Hide Statistical Analysis 50
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.445
Confidence Interval (2-Sided) 95%
-0.104 to 0.994
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2786
Estimation Comments Comparison of FVC, Day 7, 9 hour
Show Statistical Analysis 51 Hide Statistical Analysis 51
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.284
Confidence Interval (2-Sided) 95%
-0.314 to 0.882
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.3034
Estimation Comments Comparison of FVC, Day 7, 12 hour
Show Statistical Analysis 52 Hide Statistical Analysis 52
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.384
Confidence Interval (2-Sided) 95%
-0.162 to 0.929
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2766
Estimation Comments Comparison of FVC, Day 7, 24 hour
12.Primary Outcome
Title Number of Participants Who Used Rescue Medication
Hide Description 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.
Time Frame Up to Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject population was used.
Arm/Group Title Placebo GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 6 9 8
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
4
  44.4%
2
  25.0%
13.Primary Outcome
Title Number of Participants With Abnormalities in Chemistry Data of Clinical Concern
Hide Description 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.
Time Frame Up to Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject population was used.
Arm/Group Title Placebo GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 6 9 8
Measure Type: Count of Participants
Unit of Measure: Participants
Glucose, High
0
   0.0%
1
  11.1%
0
   0.0%
Inorganic phosphorus, Low
0
   0.0%
0
   0.0%
1
  12.5%
Inorganic phosphorus, High
0
   0.0%
0
   0.0%
1
  12.5%
14.Primary Outcome
Title Number of Participants With Abnormalities in Hematology Data of Clinical Concern
Hide Description 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.
Time Frame Up to Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject population was used.
Arm/Group Title Placebo GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 6 9 8
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
15.Primary Outcome
Title Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results
Hide Description 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).
Time Frame Up to Day 7 (pre dose)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject population was used.
Arm/Group Title Placebo GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 6 9 8
Measure Type: Count of Participants
Unit of Measure: Participants
Urine microscopy-RBC-Day 1
1
  16.7%
0
   0.0%
0
   0.0%
Urine microscopy-RBC-Day 7
1
  16.7%
1
  11.1%
0
   0.0%
Urine microscopy-WBC-Day 1
0
   0.0%
0
   0.0%
1
  12.5%
Urine microscopy-WBC-Day 7
1
  16.7%
1
  11.1%
1
  12.5%
16.Primary Outcome
Title Summary of Mean (0–24 Hour) and Maximum (0–24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data
Hide Description 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.
Time Frame Up to Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subject population was used.
Arm/Group Title Placebo GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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.
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 Number of Participants Analyzed 6 9 8
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Beats per minute
Maximum heart rate, Day 1
113.35
(108.13 to 118.57)
115.58
(111.24 to 119.93)
112.08
(107.62 to 116.54)
Maximum heart rate, Day 7
114.02
(101.35 to 126.69)
119.75
(109.21 to 130.30)
115.01
(104.18 to 125.84)
Mean heart rate, Day 1
71.260
(65.915 to 76.605)
73.994
(69.498 to 78.491)
70.186
(65.593 to 74.779)
Mean heart rate, Day 7
68.670
(64.101 to 73.238)
73.453
(69.610 to 77.295)
70.239
(63.313 to 74.164)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.233
Confidence Interval (2-Sided) 95%
-4.743 to 9.210
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.3333
Estimation Comments Comparison of maximum heart rate Day 1.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 5.730
Confidence Interval (2-Sided) 95%
-11.200 to 22.664
Parameter Dispersion
Type: Standard Error of the Mean
Value: 8.0907
Estimation Comments Comparison of maximum heart rate Day 7.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.272
Confidence Interval (2-Sided) 95%
-8.051 to 5.507
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.2390
Estimation Comments Comparison of maximum heart rate Day 1.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.988
Confidence Interval (2-Sided) 95%
-15.470 to 17.443
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.8616
Estimation Comments Comparison of maximum heart rate Day 7.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.734
Confidence Interval (2-Sided) 95%
-4.468 to 9.936
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.4410
Estimation Comments Comparison of mean heart rate Day 1.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.783
Confidence Interval (2-Sided) 95%
-1.372 to 10.938
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.9409
Estimation Comments Comparison of mean heart rate Day 7.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.074
Confidence Interval (2-Sided) 95%
-8.003 to 5.854
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.3103
Estimation Comments Comparison of mean heart rate Day 1.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.569
Confidence Interval (2-Sided) 95%
-4.353 to 7.490
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.8291
Estimation Comments Comparison of mean heart rate Day 7.
17.Secondary Outcome
Title Plasma Concentrations of GSK233705
Hide Description Blood samples were collected at indicated time points. 12 hour pharmacokinetic (PK) sampling was before evening dose.
Time Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population was used; this was defined as all participants in the all subjects population for whom a PK sample was obtained and analyzed.
Arm/Group Title GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 9 8
Mean (Standard Deviation)
Unit of Measure: Nanograms per milliliter
Day 1, AM dose, pre-dose Number Analyzed 9 participants 8 participants
NA [1]   (NA) NA [1]   (NA)
Day 1, AM dose, 5 minutes Number Analyzed 9 participants 8 participants
0.039  (0.0332) 0.181  (0.0948)
Day 1, AM dose, 15 minutes Number Analyzed 9 participants 8 participants
0.028  (0.0128) 0.090  (0.0331)
Day 1, AM dose, 1 hour Number Analyzed 9 participants 8 participants
0.012 [1]   (NA) 0.034  (0.0115)
Day 1, AM dose, 6 hour Number Analyzed 9 participants 8 participants
NA [1]   (NA) NA [1]   (NA)
Day 1, AM dose, 12 hour Number Analyzed 9 participants 8 participants
NA [1]   (NA) NA [1]   (NA)
Day 1, PM dose, 5 minutes Number Analyzed 8 participants 8 participants
0.070  (0.0327) 0.209  (0.1066)
Day 1, PM dose, 30 minutes Number Analyzed 8 participants 8 participants
0.024  (0.0087) 0.062  (0.0120)
Day 7, AM dose, pre-dose Number Analyzed 8 participants 8 participants
0.013  (0.0111) 0.024  (0.0070)
Day 7, AM dose, 5 minutes Number Analyzed 9 participants 8 participants
0.062  (0.0513) 0.226  (0.1257)
Day 7, AM dose, 15 minutes Number Analyzed 9 participants 8 participants
0.046  (0.0291) 0.146  (0.0724)
Day 7, AM dose, 1 hour Number Analyzed 9 participants 8 participants
0.025  (0.0119) 0.061  (0.0210)
Day 7, AM dose, 6 hour Number Analyzed 9 participants 8 participants
0.015  (0.0081) 0.028  (0.0085)
Day 7, AM dose, 12 hour Number Analyzed 9 participants 8 participants
NA [1]   (NA) 0.028  (0.0242)
Day 7, PM dose, 5 minutes Number Analyzed 9 participants 8 participants
0.068  (0.0477) 0.218  (0.1091)
Day 7, PM dose, 30 minutes Number Analyzed 9 participants 8 participants
0.028  (0.0115) 0.064  (0.0233)
[1]
NA indicates data not quantifiable.
18.Secondary Outcome
Title Urine Concentrations of GSK233705
Hide Description 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.
Time Frame Day 1 and 7 throughout 24 hours
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population was used.
Arm/Group Title GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 9 8
Mean (Standard Deviation)
Unit of Measure: Nanograms per liter
Day 1, 0-12 hours 124.6721  (35.34371) 348.9206  (110.1697)
Day 1, 12-24 hours 179.4939  (47.34615) 431.8806  (122.7514)
Day 7, 0-12 hours 316.6091  (80.41509) 629.6146  (311.2823)
Day 7, 12-24 hours 311.6291  (131.1778) 643.1492  (218.4276)
19.Secondary Outcome
Title Derived Plasma PK Parameters-area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau)
Hide Description Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning samples.
Time Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population was used.
Arm/Group Title GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 9 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hour×Nanograms per milliliter
Day 1 Number Analyzed 4 participants 7 participants
0.044
(28.2%)
0.147
(43.0%)
Day 7 Number Analyzed 9 participants 8 participants
0.189
(39.3%)
0.430
(44.5%)
20.Secondary Outcome
Title Derived Plasma PK Parameters-area Under Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-t)
Hide Description 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.
Time Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK population was used.
Arm/Group Title GSK233705 50 µg Twice Daily GSK233705 100 µg Twice Daily
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 9 8
Geometric Mean (90% Confidence Interval)
Unit of Measure: Hour×Nanograms per milliliter
Day 1
0.016
(0.011 to 0.021)
0.053
(0.038 to 0.073)
Day 7
0.018
(0.013 to 0.025)
0.056
(0.039 to 0.080)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GSK233705 50 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.139
Confidence Interval (2-Sided) 90%
0.811 to 1.601
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1939
Estimation Comments SE logs is presented as standard error of mean. Comparison of GSK233705 50 µg twice daily Day 7 versus Day 1.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection GSK233705 100 µg Twice Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.060