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A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Dose-Response Relationship of Multiple Doses of GSK2269557 Administered as a Dry Powder to Chronic Obstructive Pulmonary Disease (COPD) Patients

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ClinicalTrials.gov Identifier: NCT02130635
Recruitment Status : Completed
First Posted : May 5, 2014
Results First Posted : July 12, 2017
Last Update Posted : October 11, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Interventions Drug: GSK2269557 100 MCG
Drug: GSK2269557 500 MCG
Drug: PLACEBO
Enrollment 64
Recruitment Details  
Pre-assignment Details This study was comprised of two parts. In Part A, participants were randomized to active or placebo treatment in a 3:1 ratio and in Part B, to placebo or one of the six doses of active treatment in an equal ratio. Each part comprised a separate sample of participants.
Arm/Group Title Part A: Placebo Part A: GSK2269577 1000 µg Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description Participants received 2 inhalations of matching placebo once daily for 14 consecutive days. Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days. Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days. Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo. Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo. Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo. Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo. Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo. Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Period Title: Part A-Safety and Tolerability
Started 7 21 0 0 0 0 0 0 0
Completed 7 21 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0
Period Title: Part B-Dose-Response Relationship
Started 0 0 5 5 5 5 6 5 5
Completed 0 0 5 5 5 5 6 5 5
Not Completed 0 0 0 0 0 0 0 0 0
Arm/Group Title Part A: Placebo Part A: GSK2269577 1000 µg Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg Total
Hide Arm/Group Description Participants received 2 inhalations of matching placebo once daily for 14 consecutive days. Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days. Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days. Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo. Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo. Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo. Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo. Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo. Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg. Total of all reporting groups
Overall Number of Baseline Participants 7 21 5 5 5 5 6 5 5 64
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants 21 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 28 participants
65.1  (5.81) 60.5  (6.68) 61.7  (6.68)
[1]
Measure Description: Data provided for Part A
[2]
Measure Analysis Population Description: N=28
Age, Continuous   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 0 participants 0 participants 5 participants 5 participants 5 participants 5 participants 6 participants 5 participants 5 participants 36 participants
64.4  (4.45) 61.6  (4.56) 62.2  (8.23) 65.4  (5.81) 64.7  (7.26) 62.4  (9.24) 62.4  (6.43) 63.3  (6.34)
[1]
Measure Description: Data for Part B is presented.
[2]
Measure Analysis Population Description: N=36
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 21 participants 5 participants 5 participants 5 participants 5 participants 6 participants 5 participants 5 participants 64 participants
Female
1
  14.3%
7
  33.3%
2
  40.0%
4
  80.0%
1
  20.0%
0
   0.0%
3
  50.0%
3
  60.0%
3
  60.0%
24
  37.5%
Male
6
  85.7%
14
  66.7%
3
  60.0%
1
  20.0%
4
  80.0%
5
 100.0%
3
  50.0%
2
  40.0%
2
  40.0%
40
  62.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
White-White/Caucasian/European Heritage Number Analyzed 7 participants 21 participants 5 participants 5 participants 5 participants 5 participants 6 participants 5 participants 5 participants 64 participants
7 21 5 5 5 5 6 5 5 64
1.Primary Outcome
Title Part A: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event
Hide Description An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase >=3 x upper limit of normal (ULN), and total bilirubin >=2 x ULN or international normalized ratio >1.5. AEs were classified as potentially drug-related, based on the investigator's judgment. Refer to the general AE/SAE module for a list of AEs and SAEs.
Time Frame From the start of study treatment until follow-up (assessed for approximately 19 days)
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Hide Analysis Population Description
Safety Population: all participants who received at least one dose of study treatment.
Arm/Group Title Part A: Placebo Part A: GSK2269577 1000 µg
Hide Arm/Group Description:
Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days.
Overall Number of Participants Analyzed 7 21
Measure Type: Number
Unit of Measure: Participants
At least one AE 2 9
At least one SAE 0 1
At least one drug-related AE 2 6
2.Primary Outcome
Title Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A: Placebo Part A: GSK2269577 1000 µg
Hide Arm/Group Description:
Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days.
Overall Number of Participants Analyzed 7 21
Mean (Standard Deviation)
Unit of Measure: 10^9 cells per liter (GI/L)
WBC; Day 7/Day 8, pre-dose -0.736  (0.937) -0.080  (1.387)
WBC; Day 14, 24 h post dose -0.140  (1.220) -0.510  (0.947)
Total ANC; Day 7/Day 8, pre-dose -0.664  (0.624) -0.363  (1.342)
Total ANC; Day 14, 24 h post dose -0.153  (0.887) -0.547  (0.977)
Lymphocytes; Day 7/Day 8, pre-dose -0.033  (0.321) 0.172  (0.597)
Lymphocytes; Day 14, 24 h post dose -0.049  (0.197) 0.030  (0.245)
Monocytes; Day 7/Day 8, pre-dose -0.036  (0.074) 0.046  (0.149)
Monocytes; Day 14, 24 h post dose 0.039  (0.178) -0.022  (0.116)
Eosinophils; Day 7/Day 8, pre-dose -0.006  (0.051) 0.032  (0.074)
Eosinophils; Day 14, 24 h post dose 0.001  (0.085) 0.010  (0.075)
Basophils; Day 7/Day 8, pre-dose -0.001  (0.006) 0.006  (0.015)
Basophils; Day 14, 24 h post dose -0.003  (0.013) 0.002  (0.018)
Platelets; Day 7/Day 8, pre-dose 1.6  (20.58) 17.9  (36.44)
Platelets; Day 14, 24 h post dose 14.7  (21.80) 23.5  (37.43)
3.Primary Outcome
Title Part A: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. MCHC is one of the red blood cell (RBC) indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 h post-dose)
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Hide Analysis Population Description
Safety Population
Arm/Group Title Part A: Placebo Part A: GSK2269577 1000 µg
Hide Arm/Group Description:
Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days.
Overall Number of Participants Analyzed 7 21
Mean (Standard Deviation)
Unit of Measure: Grams/Liter (g/L)
Hemoglobin; Day 7/Day 8, pre-dose -1.3  (6.63) 1.6  (4.17)
Hemoglobin; Day 14, 24 h post dose 0.3  (6.97) 1.0  (4.12)
MCHC; Day 7/Day 8, pre-dose -5.3  (7.32) -2.2  (4.54)
MCHC; Day 14, 24 h post dose -8.4  (4.39) -2.4  (6.45)
4.Primary Outcome
Title Part A: Change From Baseline in Hematocrit at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A: Placebo Part A: GSK2269577 1000 µg
Hide Arm/Group Description:
Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days.
Overall Number of Participants Analyzed 7 21
Mean (Standard Deviation)
Unit of Measure: Ratio
Hematocrit; Day 7/Day 8, pre-dose 0.003  (0.023) 0.007  (0.013)
Hematocrit; Day 14, 24 h post dose 0.011  (0.019) 0.006  (0.016)
5.Primary Outcome
Title Part A: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A: Placebo Part A: GSK2269577 1000 µg
Hide Arm/Group Description:
Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days.
Overall Number of Participants Analyzed 7 21
Mean (Standard Deviation)
Unit of Measure: 10^12 cells/Liter (TI/L)
RBCs; Day 7/Day 8, pre-dose 0.023  (0.230) 0.060  (0.141)
RBCs; Day 14, 24 h post dose 0.119  (0.201) 0.063  (0.160)
Reticulocytes; Day 7/Day 8, pre-dose 0.005  (0.014) 0.003  (0.009)
Reticulocytes; Day 14, 24 h post dose 0.009  (0.014) 0.003  (0.010)
6.Primary Outcome
Title Part A: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. MCH is one of the red blood cell indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A: Placebo Part A: GSK2269577 1000 µg
Hide Arm/Group Description:
Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days.
Overall Number of Participants Analyzed 7 21
Mean (Standard Deviation)
Unit of Measure: Picograms (pg)
MCH; Day 7/Day 8, pre-dose -0.46  (0.602) -0.06  (0.440)
MCH; Day 14, 24 h post dose -0.76  (0.586) -0.23  (0.593)
7.Primary Outcome
Title Part A: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. MCV is one of the RBC indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A: Placebo Part A: GSK2269577 1000 µg
Hide Arm/Group Description:
Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days.
Overall Number of Participants Analyzed 7 21
Mean (Standard Deviation)
Unit of Measure: Femtoliters (fL)
MCV; Day 7/Day 8, pre-dose 0.11  (0.687) 0.43  (0.697)
MCV; Day 14, 24 h post dose 0.07  (0.848) -0.03  (1.193)
8.Primary Outcome
Title Part A: Change From Baseline in Albumin and Total Protein at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A: Placebo Part A: GSK2269577 1000 µg
Hide Arm/Group Description:
Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days.
Overall Number of Participants Analyzed 7 21
Mean (Standard Deviation)
Unit of Measure: g/L
Albumin; Day 7/Day 8, pre-dose 0.56  (2.230) 0.80  (1.576)
Albumin; Day 14, 24 h post doseTotal protein; Day 0.53  (2.379) 0.52  (2.004)
Total protein; Day 7/Day 8, pre-dose 0.56  (3.619) 1.28  (2.599)
Total protein; Day 14, 24 h post dose 0.84  (3.887) 1.15  (2.606)
9.Primary Outcome
Title Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A: Placebo Part A: GSK2269577 1000 µg
Hide Arm/Group Description:
Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days.
Overall Number of Participants Analyzed 7 21
Mean (Standard Deviation)
Unit of Measure: International Units per Liter (IU/L)
ALT; Day 7/Day 8, pre-dose 2.46  (2.585) -0.61  (2.208)
ALT; Day 14, 24 h post dose 1.51  (2.667) -0.40  (4.117)
ALP; Day 7/Day 8, pre-dose -0.64  (6.937) 1.14  (8.586)
ALP; Day 14, 24 h post dose -2.23  (6.522) -0.21  (9.785)
AST; Day 7/Day 8, pre-dose 3.14  (7.674) -1.03  (3.081)
AST; Day 14, 24 h post dose 1.83  (4.750) -0.71  (2.592)
GGT; Day 7/Day 8, pre-dose -0.91  (2.203) 0.11  (2.550)
GGT; Day 14, 24 h post dose -1.96  (2.873) -0.46  (4.187)
10.Primary Outcome
Title Part A: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A: Placebo Part A: GSK2269577 1000 µg
Hide Arm/Group Description:
Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days.
Overall Number of Participants Analyzed 7 21
Mean (Standard Deviation)
Unit of Measure: Micromoles/Liter (micromol/L)
Creatinine; Day 7/Day 8, pre-dose 2.31  (4.385) -0.62  (5.104)
Creatinine; Day 14, 24 h post dose 3.64  (6.035) 0.07  (3.259)
Direct bilirubin; Day 7/Day 8, pre-dose 0.33  (0.419) 0.04  (0.398)
Direct bilirubin; Day 14, 24 h post dose 0.27  (0.496) 0.10  (0.329)
Total bilirubin; Day 7/Day 8, pre-dose 1.23  (2.447) 0.02  (2.590)
Total bilirubin; Day 14, 24 h post dose 0.90  (2.805) 0.78  (1.720)
11.Primary Outcome
Title Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part A: Placebo Part A: GSK2269577 1000 µg
Hide Arm/Group Description:
Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days.
Overall Number of Participants Analyzed 7 21
Mean (Standard Deviation)
Unit of Measure: Millimoles per Liter (mmol/L)
Calcium; Day 7/Day 8, pre-dose 0.033  (0.0535) 0.033  (0.0617)
Calcium; Day 14, 24 h post dose 0.033  (0.0850) 0.029  (0.0588)
Glucose; Day 7/Day 8, pre-dose -0.053  (0.3333) 0.012  (0.2888)
Glucose; Day 14, 24 h post dose 0.161  (0.2659) 0.024  (0.4914)
Potassium; Day 7/Day 8, pre-dose 0.103  (0.2279) 0.011  (0.3539)
Potassium; Day 14, 24 h post dose 0.161  (0.2562) 0.065  (0.3347)
Sodium; Day 7/Day 8, pre-dose 1.21  (2.800) 0.88  (1.560)
Sodium; Day 14, 24 h post dose 0.81  (1.297) 0.83  (1.390)
BUN; Day 7/Day 8, pre-dose -0.530  (1.0830) -0.192  (0.8124)
BUN; Day 14, 24 h post dose -0.464  (1.1979) 0.111  (1.2147)
12.Primary Outcome
Title Part A: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline
Hide Description Baseline was the Day 1 pre-dose measurement. Vital signs (SBP, DBP, and HR) were measured at Day 1 (30 minutes [min] and 6 h post-dose), Day 7 (pre-dose), and Day 14 (24 h post-dose). Potential clinical concern range for SBP was <85 millimeters of mercury (mmHg) (low) and >160 mmHg (high), for DBP <45 mmHg (low) and >100 mmHg (high) and for HR <40 bpm and >110 bpm. All measurements were obtained in supine position, after a 5-minute rest. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Day 1, Day 7, and Day 14
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Safety Population
Arm/Group Title Part A: Placebo Part A: GSK2269577 1000 µg
Hide Arm/Group Description:
Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days.
Overall Number of Participants Analyzed 7 21
Measure Type: Number
Unit of Measure: Participants
SBP high 1 1
SBP low 0 0
DBP high 0 0
DBP low 1 0
HR high 0 1
HR low 0 0
13.Primary Outcome
Title Part A: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline
Hide Description Baseline was the Day 1 (pre-dose) measurement. Single 12-lead ECGs were obtained using an ECG machine that automatically calculates the HR and measures PR, QRS, QT, and corrected QT intervals. Clinical significance was judged by the investigator. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Day 1, Day 7, and Day 14
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Hide Analysis Population Description
Safety Population
Arm/Group Title Part A: Placebo Part A: GSK2269577 1000 µg
Hide Arm/Group Description:
Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days.
Overall Number of Participants Analyzed 7 21
Measure Type: Number
Unit of Measure: Participants
Normal 2 13
Abnormal - not clinically significant 5 8
Abnormal - clinically significant 0 0
14.Primary Outcome
Title Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points
Hide Description Baseline is Day 1 pre-dose. FEV1 and FVC are measures of lung function. FEV1 is defined as the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the maximum amount of air that can be forcibly blown out after a maximum inspiration. FEV1 and FVC measurements were repeated until three technically acceptable measurements (within 150 milliliters of each other) had been made. Only the best of three measurements were recorded. Baseline was the maximum of the planned pre-dose measurements on Day 1. Change from Baseline at any post-dose time point was calculated as the post-dose value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 1 (1 h post-dose), Day 7 (pre-dose and 1 h post-dose), and Day 14 (24 h post-dose)
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Safety Population
Arm/Group Title Part A: Placebo Part A: GSK2269577 1000 µg
Hide Arm/Group Description:
Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days.
Overall Number of Participants Analyzed 7 21
Mean (95% Confidence Interval)
Unit of Measure: Liters
FEV1, Day 1, 1 h post dose
0.15
(-0.01 to 0.30)
0.10
(0.02 to 0.18)
FEV1, Day 7/8, Pre-dose
0.03
(-0.09 to 0.15)
-0.04
(-0.13 to 0.05)
FEV1, Day 7/8, 1 h post dose
0.27
(0.15 to 0.39)
0.18
(0.10 to 0.26)
FEV1, Day 14, 24 h post dose
-0.01
(-0.09 to 0.06)
0.01
(-0.07 to 0.09)
FVC, Day 1, 1 h post dose
0.17
(-0.13 to 0.47)
0.16
(0.01 to 0.32)
FVC, Day 7/8, Predose
0.02
(-0.23 to 0.26)
0.00
(-0.12 to 0.13)
FVC, Day 7/8, 1 h post dose
0.33
(0.09 to 0.58)
0.22
(0.09 to 0.36)
FVC, Day 14, 24 h post dose
-0.04
(-0.30 to 0.22)
0.10
(-0.07 to 0.27)
15.Primary Outcome
Title Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14
Hide Description This outcome measure was used to estimate the inhibition levels of various doses of GSK2269557 by analyzing inflammatory cytokines IL6, IL8, and TNF alpha using Bayesian methods of statistical analysis, using non-informative prior distributions for all modeling parameters. Posterior medians (adjusted median response) and 95% credible intervals are reported here as medians and 95% confidence intervals respectively. 95% credible interval is reported as 2-sided 95% confidence in the statistical analyses. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Day 7 (pre-dose) and Day 14 (24 h post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description:
Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo.
Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Overall Number of Participants Analyzed 5 5 5 5 6 5 5
Median (95% Confidence Interval)
Unit of Measure: Picograms/milliliter (pg/mL)
IL6, Day 7/Day 8
41.30
(22.07 to 78.24)
37.40
(19.64 to 70.65)
28.23
(14.80 to 53.18)
30.82
(16.23 to 58.00)
52.23
(28.73 to 94.94)
31.25
(16.01 to 63.01)
33.40
(17.52 to 63.23)
IL6, Day 14
35.15
(17.72 to 70.01)
37.60
(18.71 to 74.49)
28.27
(14.10 to 56.22)
22.68
(11.32 to 45.13)
35.19
(18.32 to 66.93)
42.56
(20.57 to 90.25)
41.52
(20.62 to 82.81)
IL8, Day 7/Day 8
2633.21
(1401.19 to 4879.27)
2118.15
(1157.33 to 3866.74)
1860.78
(995.35 to 3499.61)
1523.63
(834.99 to 2745.90)
2650.13
(1535.07 to 4634.07)
2636.08
(1412.65 to 4978.59)
2279.48
(1205.35 to 4210.75)
IL8, Day 14
2942.28
(1375.08 to 6216.67)
2664.75
(1269.52 to 5544.49)
1879.92
(876.50 to 4056.53)
1619.12
(778.39 to 3309.81)
1356.35
(696.37 to 2645.82)
2394.65
(1125.17 to 5196.20)
2170.41
(1010.85 to 4582.03)
TNFalpha, Day 7/Day 8
3.35
(1.22 to 8.98)
1.55
(0.57 to 4.33)
1.16
(0.42 to 3.25)
1.54
(0.57 to 4.19)
7.32
(3.02 to 17.85)
3.68
(1.26 to 10.51)
2.62
(0.94 to 7.15)
TNFalpha, Day 14
2.91
(1.26 to 6.54)
3.02
(1.33 to 7.00)
1.25
(0.55 to 2.90)
1.26
(0.55 to 2.87)
3.99
(1.86 to 8.50)
3.00
(1.34 to 6.75)
1.53
(0.66 to 3.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 100 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.599
Comments Posterior Probability the True Treatment Ratio <1 for Day 7
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.39 to 2.07
Estimation Comments Comparison of IL6 concentrations at Day 7. This is the baseline corrected ratio of 100ug/placebo for day 7.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 100 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.442
Comments Posterior Probability the True Treatment Ratio <1 for Day 14
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.43 to 2.59
Estimation Comments Comparison of IL6 concentrations at Day 14. This is the baseline corrected ratio of 100ug/placebo for day 14.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 200 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.823
Comments Posterior Probability the True Treatment Ratio <1 for Day 7
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
0.30 to 1.57
Estimation Comments Comparison of IL6 concentrations at Day 7. This is the baseline corrected ratio of 200ug/placebo for day 7.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 200 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.690
Comments Posterior Probability the True Treatment Ratio <1 for Day 14
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.33 to 1.97
Estimation Comments Comparison of IL6 concentrations at Day 14. This is the baseline corrected ratio of 200ug/placebo for day 14.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 500 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.764
Comments Posterior Probability the True Treatment Ratio <1 for Day 7
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.33 to 1.71
Estimation Comments Comparison of IL6 concentrations at Day 7. This is the baseline corrected ratio of 500ug/placebo for day 7.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 500 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.841
Comments Posterior Probability the True Treatment Ratio <1 for Day 14
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.27 to 1.56
Estimation Comments Comparison of IL6 concentrations at Day 14. This is the baseline corrected ratio of 500ug/placebo for day 14.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 100 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.702
Comments Posterior Probability the True Treatment Ratio <1 for Day 7
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.35 to 1.81
Estimation Comments Comparison of IL8 concentrations at Day 7.This is the baseline corrected ratio of 100ug/placebo for day 7.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 100 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.578
Comments Posterior Probability the True Treatment Ratio <1 for Day 14
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.33 to 2.47
Estimation Comments Comparison of IL8 concentrations at Day 14. This is the baseline corrected ratio of 100ug/placebo for day 14.
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 200 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.783
Comments Posterior Probability the True Treatment Ratio <1 for Day 7
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.29 to 1.70
Estimation Comments Comparison of IL8 concentrations at Day 7. This is the baseline corrected ratio of 200ug/placebo for day 7.
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 200 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.797
Comments Posterior Probability the True Treatment Ratio <1 for Day 14
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.22 to 1.87
Estimation Comments Comparison of IL8 concentrations at Day 14. This is the baseline corrected ratio of 200ug/placebo for day 14.
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 500 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.919
Comments Posterior Probability the True Treatment Ratio <1 for Day 7
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.27 to 1.26
Estimation Comments Comparison of IL8 concentrations at Day 7. This is the baseline corrected ratio of 500ug/placebo for day 7.
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 500 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.892
Comments Posterior Probability the True Treatment Ratio <1 for Day 14
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.55
Confidence Interval (2-Sided) 95%
0.21 to 1.43
Estimation Comments Comparison of IL8 concentrations at Day 14. This is the baseline corrected ratio of 500ug/placebo for day 14.
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 100 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.860
Comments Posterior Probability the True Treatment Ratio <1 for Day 7
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.11 to 1.93
Estimation Comments Comparison of TNFalpha concentrations at Day 7. This is the baseline corrected ratio of 100ug/placebo for day 7.
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 100 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.463
Comments Posterior Probability the True Treatment Ratio <1 for Day 14
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.38 to 2.86
Estimation Comments Comparison of TNFalpha concentrations at Day 14. This is the baseline corrected ratio of 100ug/placebo for day 14.
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 200 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.932
Comments Posterior Probability the True Treatment Ratio <1 for Day 7
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
0.09 to 1.42
Estimation Comments Comparison of TNFalpha concentrations at Day 7. This is the baseline corrected ratio of 200ug/placebo for day 7.
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 200 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.952
Comments Posterior Probability the True Treatment Ratio <1 for Day 14
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.43
Confidence Interval (2-Sided) 95%
0.16 to 1.17
Estimation Comments Comparison of TNFalpha concentrations at Day 14. This is the baseline corrected ratio of 200ug/placebo for day 14.
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 500 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.873
Comments Posterior Probability the True Treatment Ratio <1 for Day 7
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.46
Confidence Interval (2-Sided) 95%
0.12 to 1.81
Estimation Comments Comparison of TNFalpha concentrations at Day 7. This is the baseline corrected ratio of 500ug/placebo for day 7.
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 500 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.953
Comments Posterior Probability the True Treatment Ratio <1 for Day 14
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.43
Confidence Interval (2-Sided) 95%
0.16 to 1.16
Estimation Comments Comparison of TNFalpha concentrations at Day 14. This is the baseline corrected ratio of 500ug/placebo for day 14.
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 700 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.281
Comments Posterior Probability the True Treatment Ratio <1 for Day 7
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio9
Estimated Value 1.26
Confidence Interval (2-Sided) 95%
0.56 to 2.82
Estimation Comments Comparison of IL6 concentrations at Day 7. This is the baseline corrected ratio of 700ug/placebo for day 7.
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 700 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.500
Comments Posterior Probability the True Treatment Ratio <1 for Day 14
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.42 to 2.35
Estimation Comments Comparison of IL6 concentrations at Day 14. This is the baseline corrected ratio of 700ug/placebo for day 14.
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 1000 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.744
Comments Posterior Probability the True Treatment Ratio <1 for Day 7
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.32 to 1.77
Estimation Comments Comparison of IL6 concentrations at Day 7. This is the baseline corrected ratio of 1000ug/placebo for day 7.
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 1000 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.334
Comments Posterior Probability the True Treatment Ratio <1 for Day 14
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 1.21
Confidence Interval (2-Sided) 95%
0.49 to 3.04
Estimation Comments Comparison of IL6 concentrations at Day 14. This is the baseline corrected ratio of 1000ug/placebo for day 14.
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 2000 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.698
Comments Posterior Probability the True Treatment Ratio <1 for Day 7
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.35 to 1.85
Estimation Comments Comparison of IL6 concentrations at Day 7. This is the baseline corrected ratio of 2000ug/placebo for day 7.
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 2000 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.353
Comments Posterior Probability the True Treatment Ratio <1 for Day 14
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 1.18
Confidence Interval (2-Sided) 95%
0.48 to 2.88
Estimation Comments Comparison of IL6 concentrations at Day 14. This is the baseline corrected ratio of 2000ug/placebo for day 14.
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 700 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.489
Comments Posterior Probability the True Treatment Ratio <1 for Day 7
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio9
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.45 to 2.26
Estimation Comments Comparison of IL8 concentrations at Day 7. This is the baseline corrected ratio of 700ug/placebo for day 7.
Show Statistical Analysis 26 Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 700 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.940
Comments Posterior Probability the True Treatment Ratio <1 for Day 14
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.46
Confidence Interval (2-Sided) 95%
0.17 to 1.23
Estimation Comments Comparison of IL8 concentrations at Day 14. This is the baseline corrected ratio of 700ug/placebo for day 14.
Show Statistical Analysis 27 Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 1000 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.495
Comments Posterior Probability the True Treatment Ratio <1 for Day 7
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.42 to 2.40
Estimation Comments Comparison of IL8 concentrations at Day 7. This is the baseline corrected ratio of 1000ug/placebo for day 7.
Show Statistical Analysis 28 Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 1000 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.647
Comments Posterior Probability the True Treatment Ratio <1 for Day 14
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.28 to 2.37
Estimation Comments Comparison of IL8 concentrations at Day 14. This is the baseline corrected ratio of 1000ug/placebo for day 14.
Show Statistical Analysis 29 Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 2000 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.646
Comments Posterior Probability the True Treatment Ratio <1 for Day 7
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.40 to 1.86
Estimation Comments Comparison of IL8 concentrations at Day 7. This is the baseline corrected ratio of 2000ug/placebo for day 7.
Show Statistical Analysis 30 Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 2000 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.741
Comments Posterior Probability the True Treatment Ratio <1 for Day 14
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.29 to 1.90
Estimation Comments Comparison of IL8 concentrations at Day 14. This is the baseline corrected ratio of 2000ug/placebo for day 14.
Show Statistical Analysis 31 Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 700 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.109
Comments Posterior Probability the True Treatment Ratio <1 for Day 7
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio9
Estimated Value 2.18
Confidence Interval (2-Sided) 95%
0.62 to 7.95
Estimation Comments Comparison of TNFalpha concentrations at Day 7. This is the baseline corrected ratio of 700ug/placebo for day 7.
Show Statistical Analysis 32 Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 700 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.240
Comments Posterior Probability the True Treatment Ratio <1 for Day 14
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 1.37
Confidence Interval (2-Sided) 95%
0.55 to 3.45
Estimation Comments Comparison of TNFalpha concentrations at Day 14. This is the baseline corrected ratio of 700ug/placebo for day 14.
Show Statistical Analysis 33 Hide Statistical Analysis 33
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 1000 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.447
Comments Posterior Probability the True Treatment Ratio <1 for Day 7
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.27 to 4.44
Estimation Comments Comparison of TNFalpha concentrations at Day 7. This is the baseline corrected ratio of 1000ug/placebo for day 7.
Show Statistical Analysis 34 Hide Statistical Analysis 34
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 1000 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.472
Comments Posterior Probability the True Treatment Ratio <1 for Day 14
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.39 to 2.74
Estimation Comments Comparison of TNFalpha concentrations at Day 14. This is the baseline corrected ratio of 1000ug/placebo for day 14.
Show Statistical Analysis 35 Hide Statistical Analysis 35
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 2000 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.698
Comments Posterior Probability the True Treatment Ratio <1 for Day 7
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.21 to 2.90
Estimation Comments Comparison of TNFalpha concentrations at Day 7. This is the baseline corrected ratio of 2000ug/placebo for day 7.
Show Statistical Analysis 36 Hide Statistical Analysis 36
Statistical Analysis Overview Comparison Group Selection Part B: Placebo, Part B: GSK2269577 2000 µg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.911
Comments Posterior Probability the True Treatment Ratio <1 for Day 14
Method Bayesian repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Median Ratio
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
0.21 to 1.37
Estimation Comments Comparison of TNFalpha concentrations at Day 14. This is the baseline corrected ratio of 2000ug/placebo for day 14.
16.Secondary Outcome
Title Part A: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose
Hide Description A 2 mL blood sample for pharmacokinetic (PK) analysis was collected at each of the indicated time point. Only those participants who were available at the indicated time points were analyzed (represented by n=X in the category titles). A value of NA indicates that the geometric mean or 95% confidence interval is not available.
Time Frame Day 1 (Pre-dose, 5 min, 30 min, 1, 2, 4 & 6 hours post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population: participants in the Safety Population for whom a PK sample was obtained and analyzed.
Arm/Group Title Part A: GSK2269577 1000 µg
Hide Arm/Group Description:
Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days.
Overall Number of Participants Analyzed 21
Geometric Mean (95% Confidence Interval)
Unit of Measure: pg/mL
Pre-dose; n=0
NA [1] 
(NA to NA)
5 min; n=21
386.2
(287.5 to 518.7)
30 min; n=21
337.2
(274.6 to 414.0)
1 h; n=21
379.1
(320.2 to 448.9)
2 h; n=21
531.1
(448.2 to 629.4)
4 h; n=21
419.5
(357.6 to 492.1)
6 h; n=21
334.4
(287.0 to 389.6)
[1]
A value of NA indicates that the geometric mean or 95% confidence interval is not available.
17.Secondary Outcome
Title Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose
Hide Description A 2 mL blood sample for pharmacokinetic (PK) analysis was collected at each of the indicated time point. Concentration measurements were log-transformed. Only those participants who were available at the indicated time points were analyzed (represented by n=X,X in the category titles). A value of NA indicates that the geometric mean or 95% confidence interval is not available.
Time Frame Pre-dose, and 5 min, 30 min, 1 h, 2 h, 4 h, and 6 h post-dose on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description:
Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo.
Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Overall Number of Participants Analyzed 5 5 5 6 5 5
Geometric Mean (95% Confidence Interval)
Unit of Measure: pg/mL
Pre-dose; n=0,0,0,0,0,0
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
5 min; n=5,5,5,6,5,5
55.3
(33.7 to 90.7)
80.4
(38.4 to 168.2)
173.1
(88.4 to 339.0)
466.6
(147.3 to 1478.0)
853.4
(380.2 to 1915.6)
982.9
(311.1 to 3105.3)
30 min; n=5,5,5,6,5,5
51.7
(36.2 to 74.1)
73.8
(41.6 to 130.8)
203
(111.2 to 370.5)
402.3
(218.0 to 742.5)
556.9
(384.8 to 806.0)
1011.6
(757.1 to 1351.6)
1 h; n=5,5,5,6,5,5
61.3
(45.7 to 82.3)
77.2
(44.1 to 135.2)
253.2
(155.0 to 413.8)
429.1
(294.2 to 626.0)
599.7
(370.5 to 970.7)
1203.3
(799.1 to 1812.0)
2 h; n=5,5,5,6,5,5
60.6
(44.8 to 81.9)
88.8
(60.2 to 130.9)
300.9
(173.7 to 521.1)
556.7
(372.4 to 832.3)
672.3
(434.0 to 1041.5)
1402
(892.8 to 2201.4)
4 h; n=5,5,5,6,5,5
45.0
(33.1 to 61.2)
73.4
(60.5 to 89.1)
251
(146.0 to 431.6)
391.6
(303.3 to 505.5)
468.7
(305.5 to 719.2)
1098.5
(781.9 to 1543.2)
6 h; n=5,5,5,6,5,5
38.3
(29.7 to 49.5)
63.8
(50.7 to 80.3)
201.5
(128.3 to 316.6)
294.6
(222.3 to 390.4)
466.5
(273.1 to 796.6)
900.8
(723.8 to 1121.0)
[1]
A value of NA indicates that the geometric mean or 95% confidence interval is not available.
18.Secondary Outcome
Title Part A: Maximum Observed Plasma Concentration (Cmax) of GSK2269577 on Day 7
Hide Description Blood samples were collected to determine the plasma concentrations of GSK2269577 immediately after dosing on Day 7. Day 7 sampling could be done on Day 7 or Day 8.
Time Frame Day 7 immediately after dosing
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title Part A: GSK2269577 1000 µg
Hide Arm/Group Description:
Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days.
Overall Number of Participants Analyzed 21
Geometric Mean (95% Confidence Interval)
Unit of Measure: pg/mL
1109.1
(901.5 to 1364.5)
19.Secondary Outcome
Title Part B: Maximum Observed Plasma Concentration (Cmax) of GSK2269577 on Day 7
Hide Description Blood samples were collected to determine the plasma concentrations of GSK2269577 immediately after dosing on Day 7. Concentration values were log-transformed. Day 7 sampling could be done on Day 7 or Day 8.
Time Frame Day 7 immediately after dosing
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description:
Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo.
Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Overall Number of Participants Analyzed 5 5 5 6 5 5
Geometric Mean (95% Confidence Interval)
Unit of Measure: pg/mL
109.6
(62.6 to 191.8)
203.4
(140.3 to 294.8)
511.8
(233.2 to 1123.3)
1022.2
(623.7 to 1675.2)
1655.1
(803.2 to 3410.4)
2923.4
(1769.4 to 4830.0)
20.Secondary Outcome
Title Part A: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15
Hide Description Blood samples were collected to determine the (trough) plasma concentration of GSK2269577 on Day 7 (pre-dose) and Day 15 (24 hours after dosing on Day 14). Day 7 assessments could be done either on Day 7 or on Day 8.
Time Frame Day 7 and Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title Part A: GSK2269577 1000 µg
Hide Arm/Group Description:
Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days.
Overall Number of Participants Analyzed 21
Geometric Mean (95% Confidence Interval)
Unit of Measure: pg/mL
Day 7/Day 8
604.1
(496.6 to 735.0)
Day 15
711.2
(561.8 to 900.3)
21.Secondary Outcome
Title Part B: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15
Hide Description Blood samples were collected to determine the (trough) plasma concentration of GSK2269577 on Day 7 (pre-dose) and Day 15 (24 hours after dosing on Day 14). Day 7 assessments could be done either on Day 7 or on Day 8.
Time Frame Day 7 and Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description:
Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo.
Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Overall Number of Participants Analyzed 5 5 5 6 5 5
Geometric Mean (95% Confidence Interval)
Unit of Measure: pg/mL
Day 7/Day 8
55.3
(41.22 to 74.21)
119.17
(78.47 to 180.97)
314.38
(182.64 to 541.16)
588.09
(486.63 to 710.69)
724.33
(581.37 to 902.45)
1468.94
(1000.50 to 2156.70)
Day 15
74.93
(48.26 to 116.33)
128.71
(92.02 to 180.03)
237.36
(66.38 to 848.74)
665.9
(497.61 to 891.10)
1218.5
(985.88 to 1506.01)
1767.34
(1079.72 to 2892.86)
22.Secondary Outcome
Title Part B: Number of Times Rescue Medication Was Used by Participants Daily, During the Treatment Period
Hide Description Rescue medication was identified from concomitant medication records and the patient diaries which were provided to the participants to record data throughout the treatment period. Only participants who used rescue medication were analyzed. The value NA indicates that the standard deviation could not be calculated as only one participant was analyzed.
Time Frame Day 1 to Day 15
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Safety Population
Arm/Group Title Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description:
Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo.
Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Overall Number of Participants Analyzed 3 1 1 0 1 3 1
Mean (Standard Deviation)
Unit of Measure: Number of times
2.00  (0.00) 2.3 [1]   (NA) 2.2 [1]   (NA) 1.0 [1]   (NA) 1.4  (0.63) 1.0 [1]   (NA)
[1]
The value NA indicates that the standard deviation could not be calculated as only one participant was analyzed.
23.Secondary Outcome
Title Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event
Hide Description An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase >=3 x upper limit of normal (ULN), and total bilirubin >=2 x ULN or international normalized ratio >1.5. AEs were classified as potentially drug-related, based on the investigator's judgment. Refer to the general AE/SAE module for a list of AEs and SAEs.
Time Frame From the start of study treatment until follow-up (assessed for approximately 19 days)
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Safety Population
Arm/Group Title Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description:
Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo.
Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Overall Number of Participants Analyzed 5 5 5 5 6 5 5
Measure Type: Number
Unit of Measure: Participants
At least one AE 3 3 2 1 3 4 2
At least one SAE 0 0 0 0 0 0 0
At least one drug-related AE 0 0 1 0 3 4 2
24.Secondary Outcome
Title Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
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Hide Analysis Population Description
Safety Population
Arm/Group Title Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description:
Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo.
Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Overall Number of Participants Analyzed 5 5 5 5 6 5 5
Mean (Standard Deviation)
Unit of Measure: 10^9 cells per liter (GI/L)
Basophils; Day 7/Day 8, pre-dose 0.014  (0.0241) -0.002  (0.0228) 0.01  (0.0187) 0.004  (0.0182) 0.007  (0.0052) -0.005  (0.01) 0  (0.01)
Basophils; Day 14, 24 h post dose 0.004  (0.0167) -0.006  (0.0261) 0.01  (0.0122) -0.002  (0.0192) 0.007  (0.0175) -0.008  (0.0189) 0.01  (0.0122)
Eosinophils; Day 7/Day 8, pre-dose -0.002  (0.0576) 0.01  (0.0485) -0.034  (0.0702) -0.026  (0.0498) 0.022  (0.1289) -0.002  (0.0287) 0.012  (0.0438)
Eosinophils; Day 14, 24 h post dose 0.046  (0.0472) -0.01  (0.0292) -0.046  (0.0378) -0.054  (0.1498) 0.025  (0.1078) 0.023  (0.0222) 0.022  (0.0396)
Lymphocytes; Day 7/Day 8, pre-dose 0.242  (0.4797) -0.178  (0.5657) -0.022  (0.1326) -0.094  (0.3092) 0.093  (0.2813) -0.118  (0.3223) -0.218  (0.6236)
Lymphocytes; Day 14, 24 h post dose -0.09  (0.4499) -0.264  (0.3134) -0.216  (0.208) 0.092  (0.9722) 0.21  (0.3855) -0.243  (0.3054) -0.398  (0.736)
Monocytes; Day 7/Day 8, pre-dose -0.062  (0.0867) 0.05  (0.0941) -0.02  (0.0806) 0.05  (0.2108) 0.018  (0.1209) 0.165  (0.5166) -0.08  (0.1398)
Monocytes; Day 14, 24 h post dose -0.022  (0.0676) -0.012  (0.0926) -0.036  (0.0829) -0.004  (0.1313) 0.03  (0.0699) 0.108  (0.3437) -0.11  (0.0834)
Platelets; Day 7/Day 8, pre-dose -13.8  (14.22) -0.8  (18.07) 10  (24.52) 15.6  (17.78) 11.7  (15.41) 26.5  (32.77) -0.6  (14.4)
Platelets; Day 14, 24 h post dose -3.3  (22.25) -13  (26.52) -7.2  (20.41) -1.4  (44.86) 7  (19.81) -8.3  (51.57) -11.4  (29.39)
WBC; Day 7/Day 8, pre-dose 0.372  (1.5852) -0.024  (1.1519) 0.102  (1.1107) 0.926  (3.1314) 0.497  (0.8673) 0.5  (2.676) -0.802  (0.7889)
WBC; Day 14, 24 h post dose -0.49  (0.5204) -0.864  (1.4151) -0.164  (0.7907) -0.178  (2.2899) 0.648  (1.143) 0.825  (1.6016) -1.012  (1.3388)
Total ANC; Day 7/Day 8, pre-dose 0.164  (0.9782) 0.09  (0.6553) 0.17  (1.0481) 1.018  (2.6669) 0.335  (0.5921) 0.448  (2.153) -0.51  (0.285)
Total ANC; Day 14, 24 h post dose -0.44  (0.4288) -0.538  (1.1027) 0.134  (0.801) -0.18  (1.469) 0.385  (1.2151) 0.958  (1.8925) -0.51  (0.7931)
25.Secondary Outcome
Title Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. MCHC is one of the red blood cell (RBC) indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description:
Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo.
Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Overall Number of Participants Analyzed 5 5 5 5 6 5 5
Mean (Standard Deviation)
Unit of Measure: g/L
Hemoglobin; Day 7/Day 8, pre-dose 3  (2.55) 0.8  (5.76) 3.8  (6.76) 1  (4.74) 0.3  (5.65) 6  (5.89) 1  (3.39)
Hemoglobin; Day 14, 24 h post dose 4.2  (6.14) -1.2  (6.14) -0.6  (8.02) -2  (6.86) -2.2  (2.14) -0.3  (4.65) -0.2  (4.44)
MCHC; Day 7/Day 8, pre-dose -2.4  (2.07) -0.6  (8.17) -4.0  (7.31) -4.4  (9.61) 0.5  (5.17) 3.3  (8.18) 7.8  (10.85)
MCHC; Day 14, 24 h post dose 3.8  (5.07) -2.6  (3.51) -4.4  (8.73) 3.0  (4.00) 2.5  (3.83) -8.5  (7.59) 1.6  (11.76)
26.Secondary Outcome
Title Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Hide Outcome Measure Data
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Safety Population
Arm/Group Title Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description:
Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo.
Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Overall Number of Participants Analyzed 5 5 5 5 6 4 5
Mean (Standard Deviation)
Unit of Measure: 10^12 cells/Liter (TI/L)
RBC; Day 7/Day 8, pre-dose 0.076  (0.1148) 0.036  (0.1549) 0.18  (0.2703) 0.058  (0.1314) -0.023  (0.1508) 0.14  (0.0879) -0.058  (0.1252)
RBC; Day 14, 24 h post dose 0.11  (0.1891) -0.038  (0.1663) 0.034  (0.1785) -0.07  (0.1815) -0.083  (0.0958) 0.042  (0.1031) -0.084  (0.1496)
Reticulocytes; Day 7/Day 8, pre-dose -0.00064  (0.01328) 0.00714  (0.020838) 0.01298  (0.011129) 0.01258  (0.014565) 0.00397  (0.008856) 0.00882  (0.018576) 0.01792  (0.012824)
Reticulocytes; Day 14, 24 h post dose 0.0034  (0.014934) 0.0006  (0.010183) 0.01032  (0.015404) 0.0156  (0.013092) -0.00172  (0.005382) -0.01063  (0.018329) 0.00884  (0.015546)
27.Secondary Outcome
Title Part B: Change From Baseline in Hematocrit at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Hide Outcome Measure Data
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Safety Population
Arm/Group Title Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description:
Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo.
Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Overall Number of Participants Analyzed 5 5 5 5 6 5 5
Mean (Standard Deviation)
Unit of Measure: Ratio
Day 7/Day 8, pre-dose 0.012  (0.0084) 0.004  (0.0182) 0.018  (0.0259) 0.01  (0.01) 0  (0.0141) 0.015  (0.0058) -0.010  (0.0235)
Day 14, 24 h post dose 0.008  (0.0217) 0  (0.0212) 0.006  (0.0152) -0.012  (0.0217) -0.01  (0.0063) 0.01  (0.0082) -0.004  (0.0207)
28.Secondary Outcome
Title Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. MCH is one of the red blood cell indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description:
Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo.
Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Overall Number of Participants Analyzed 5 5 5 5 6 4 5
Mean (Standard Deviation)
Unit of Measure: pg
Day 7/Day 8, pre-dose 0.18  (0.415) -0.06  (0.397) -0.36  (0.351) -0.08  (0.669) 0.2  (0.529) 0.35  (0.961) 0.58  (0.46)
Day 14, 24 h post dose 0.18  (0.626) 0.02  (0.259) -0.34  (0.74) 0.12  (0.396) 0.1  (0.363) -0.33  (0.754) 0.52  (0.268)
29.Secondary Outcome
Title Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. MCV is one of the RBC indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description:
Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo.
Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Overall Number of Participants Analyzed 5 5 5 5 6 4 5
Mean (Standard Deviation)
Unit of Measure: fL
MCV; Day 7/Day 8, pre-dose 1.24  (0.706) -0.14  (1.794) -0.12  (1.708) 0.88  (1.085) 0.42  (2.302) 0.20  (0.583) -0.70  (2.719)
MCV; Day 14, 24 h post dose -0.66  (1.537) 0.80  (1.257) 0.26  (1.935) -0.62  (1.281) -0.53  (1.601) 1.53  (0.699) 0.98  (3.155)
30.Secondary Outcome
Title Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description:
Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo.
Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Overall Number of Participants Analyzed 5 5 5 5 6 5 5
Mean (Standard Deviation)
Unit of Measure: g/L
Albumin; Day 7/Day 8, pre-dose 0.96  (1.773) 1.22  (1.571) 0.96  (3.012) 0.88  (0.887) -0.6  (1.814) 1.18  (1.069) 0.3  (1.49)
Albumin; Day 14, 24 h post dose 0.9  (2.965) 0.7  (2.134) -0.12  (2.538) -1.16  (2.157) -1.13  (1.365) 0.44  (1.001) 0.26  (1.187)
Total protein; Day 7/Day 8, pre-dose 1.34  (2.46) 0.72  (1.203) 2.22  (4.953) 0.98  (2.039) -1.4  (2.662) 1.78  (2.338) 1.12  (1.571)
Total protein; Day 14, 24 h post dose 0.96  (3.392) 0.96  (2.393) -0.16  (3.737) -1.96  (3.635) -2.13  (2.156) 0.72  (1.154) 0.7  (2.277)
31.Secondary Outcome
Title Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description:
Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo.
Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Overall Number of Participants Analyzed 5 5 5 5 6 5 5
Mean (Standard Deviation)
Unit of Measure: International Units per Liter (IU/L)
ALP; Day 7/Day 8, pre-dose 1.88  (5.45) 1.62  (5.756) 1.64  (7.946) 5.7  (9.986) -0.95  (7.807) -0.92  (22.572) 1.66  (5.465)
ALP; Day 14, 24 h post dose 1.54  (4.503) 4.78  (7.294) -0.2  (6.109) 0.26  (9.829) -1.1  (8.535) -5.34  (19.016) 5.2  (4.038)
ALT; Day 7/Day 8, pre-dose 1.58  (2.24) 3.66  (6.057) -2.44  (7.23) 2.6  (4.994) -0.1  (2.994) -2.4  (5.036) 1.42  (2.791)
ALT; Day 14, 24 h post dose 0.36  (2.268) 2.18  (3.17) -2.76  (6.176) 0.84  (5.223) -0.72  (4.63) -2.86  (5.478) 1.58  (3.754)
AST; Day 7/Day 8, pre-dose 1.38  (2.464) 3.76  (11.142) -0.42  (3.13) 0.26  (5.185) -0.22  (3.672) -2.56  (5.607) 3.04  (2.048)
AST; Day 14, 24 h post dose 0.44  (1.691) 0.16  (1.673) -2.44  (3.443) -1.64  (6.027) 0.02  (3.129) -1.66  (4.536) 2.66  (1.25)
GGT; Day 7/Day 8, pre-dose -0.6  (2.119) -0.3  (1.856) -0.96  (4.556) -0.3  (4.471) 1.88  (4.747) -3.18  (9.7) 0.74  (1.141)
GGT; Day 14, 24 h post dose -0.64  (0.934) 0.1  (2.625) -2.64  (6.532) -0.72  (5.485) 1.52  (5.783) -6.16  (17.113) 0.54  (1.923)
32.Secondary Outcome
Title Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description:
Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo.
Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Overall Number of Participants Analyzed 5 5 5 5 6 5 5
Mean (Standard Deviation)
Unit of Measure: Micromoles/Liter (micromol/L)
Direct bilirubin; Day 7/Day 8, pre-dose -0.02  (0.327) 0.24  (0.493) -0.28  (0.881) 0.16  (0.261) 0.23  (0.65) -0.18  (1.36) -0.32  (0.37)
Direct bilirubin; Day 14, 24 h post dose -0.1  (0.453) -0.02  (0.192) -0.58  (0.581) 0.22  (0.409) 0.2  (0.429) 0.02  (0.554) -0.14  (0.456)
Total bilirubin; Day 7/Day 8, pre-dose 0.28  (2.255) 0.56  (2.151) -0.7  (4.049) 0.72  (2.196) 1.08  (2.775) -0.86  (1.75) -1.5  (1.739)
Total bilirubin; Day 14, 24 h post dose -0.5  (3.389) 0.08  (0.87) -2.08  (2.387) 0.52  (2.7) 1.22  (3.008) 0.5  (2.804) -1.06  (1.479)
Creatinine; Day 7/Day 8, pre-dose 4.52  (4.533) 1.6  (3.77) 4.38  (2.217) -0.3  (4.567) 0.52  (4.397) 3.48  (3.084) 0.76  (5.421)
Creatinine; Day 14, 24 h post dose 1.58  (7.276) 0.76  (3.319) 4.84  (4.636) -0.46  (6.98) 2.05  (3.17) 1.36  (2.545) 1.42  (5.058)
33.Secondary Outcome
Title Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points
Hide Description Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description:
Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo.
Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Overall Number of Participants Analyzed 5 5 5 5 6 5 5
Mean (Standard Deviation)
Unit of Measure: Millimoles per Liter (mmol/L)
Calcium; Day 7/Day 8, pre-dose 0.048  (0.0444) 0.044  (0.0397) 0.06  (0.0579) 0.01  (0.0648) -0.008  (0.0655) 0.066  (0.0811) 0.044  (0.0365)
Calcium; Day 14, 24 h post dose 0.024  (0.0865) -0.012  (0.0482) 0.05  (0.0696) -0.01  (0.0758) -0.042  (0.0422) 0.03  (0.0292) 0.036  (0.0568)
Glucose; Day 7/Day 8, pre-dose -0.06  (0.2939) 0.054  (0.4057) 0.05  (0.1937) -0.43  (1.4084) -0.11  (0.5658) 0.11  (0.4369) -0.246  (0.273)
Glucose; Day 14, 24 h post dose -0.086  (0.3743) -0.142  (0.3746) 0.26  (0.5456) 0.054  (0.2294) -0.34  (0.7332) -0.076  (0.3518) -0.314  (0.3871)
Potassium; Day 7/Day 8, pre-dose 0.246  (0.3088) 0.09  (0.2793) 0.434  (0.5451) -0.204  (0.2563) 0.135  (0.3172) 0.276  (0.3566) 0.192  (0.4587)
Potassium; Day 14, 24 h post dose 0.19  (0.1944) 0.12  (0.4282) 0.336  (0.5268) -0.128  (0.3241) 0.013  (0.203) 0.14  (0.1259) 0.072  (0.5946)
Sodium; Day 7/Day 8, pre-dose 0  (1.206) 0.6  (1.626) -0.12  (1.714) 1.18  (1.139) -0.33  (2.072) 0.7  (1.815) -0.84  (2.137)
Sodium; Day 14, 24 h post dose -0.16  (1.301) -0.04  (3.233) 0.58  (1.399) 0.46  (1.447) -0.18  (2.515) 1.06  (1.074) -0.4  (2.72)
Urea/BUN; Day 7/Day 8, pre-dose 0.314  (0.7077) -0.504  (0.6955) 0.342  (0.8193) -0.91  (1.0653) -0.29  (0.4396) -0.244  (1.2909) 0.162  (1.2285)
Urea/BUN; Day 14, 24 h post dose -0.232  (0.3592) -0.124  (0.7502) 0.142  (1.0269) -0.906  (1.6431) -0.335  (0.2793) -0.364  (0.8554) 0.186  (2.0478)
34.Secondary Outcome
Title Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline
Hide Description Baseline was the Day 1 pre-dose measurement. Vital signs (SBP, DBP, and HR) were measured at Day 1 (30 minutes [min] and 6 h post-dose), Day 7 (pre-dose), and Day 14 (24 h post-dose). All measurements were obtained in supine position, after a 5-minute rest. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Day 1, Day 7, and Day 14
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Safety Population
Arm/Group Title Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description:
Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo.
Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Overall Number of Participants Analyzed 5 5 5 5 6 5 5
Measure Type: Number
Unit of Measure: Participants
SBP high 0 0 1 1 1 0 0
SBP low 0 0 0 0 0 0 0
DBP high 0 0 0 0 0 0 0
DBP low 0 0 0 0 0 0 0
HR high 0 0 0 0 0 0 0
HR low 0 0 0 0 0 0 0
35.Secondary Outcome
Title Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline
Hide Description Baseline was the Day 1 (pre-dose) measurement. Single 12-lead ECGs were obtained using an ECG machine that automatically calculates the HR and measures PR, QRS, QT, and corrected QT intervals. Day 7 assessments could be conducted on Day 7 or Day 8.
Time Frame Day 1, Day 7, and Day 14
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Safety Population
Arm/Group Title Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description:
Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo.
Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Overall Number of Participants Analyzed 5 5 5 5 6 5 5
Measure Type: Number
Unit of Measure: Participants
Normal 4 5 3 2 5 5 4
Abnormal - not clinically significant 1 0 2 3 1 0 1
Abnormal - clinically significant 0 0 0 0 0 0 0
36.Secondary Outcome
Title Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up
Hide Description FEV1 and FVC are measures of lung function. FEV1 is defined as the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the maximum amount of air that can be forcibly blown out after a maximum inspiration. FEV1 and FVC measurements were repeated until three technically acceptable measurements (within 150 milliliters of each other) had been made. Only the best of three measurements were recorded.
Time Frame Screening (up to 30 days prior to Day 1) and Follow-up (approximately Day 19)
Hide Outcome Measure Data
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Safety Population
Arm/Group Title Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description:
Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.
Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo.
Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo.
Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
Overall Number of Participants Analyzed 5 5 5 5 6 5 5
Mean (95% Confidence Interval)
Unit of Measure: Liters
FEV1, Screening
1.586
(1.093 to 2.079)
1.387
(0.783 to 1.99)
1.533
(0.784 to 2.282)
1.558
(0.916 to 2.199)
1.573
(1.092 to 2.055)
1.36
(1.126 to 1.594)
1.407
(0.768 to 2.046)
FEV1, Follow-up
1.494
(1.174 to 1.813)
1.272
(0.69 to 1.855)
1.523
(0.775 to 2.271)
1.34
(1.092 to 1.589)
1.501
(0.989 to 2.013)
1.405
(0.948 to 1.861)
1.431
(0.834 to 2.028)
FVC, Screening
3.05
(2.476 to 3.624)
3.08
(1.901 to 4.259)
3.632
(2.585 to 4.679)
4.348
(3.565 to 5.131)
3.277
(2.389 to 4.164)
2.958
(1.6 to 4.316)
3.156
(2.099 to 4.213)
FVC, Follow-up
2.96
(2.432 to 3.488)
3.042
(1.809 to 4.275)
3.764
(2.533 to 4.995)
4.192
(3.527 to 4.857)
3.137
(2.057 to 4.217)
3.03
(1.691 to 4.369)
3.192
(1.968 to 4.416)
Time Frame On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occurring from the start of treatment until follow-up (up to approximately 19 days), are reported.
Adverse Event Reporting Description SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants who received at least one dose of study treatment.
 
Arm/Group Title Part A: Placebo Part A: GSK2269577 1000 µg Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Hide Arm/Group Description Participants received 2 inhalations of matching placebo once daily for 14 consecutive days. Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days. Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days. Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo. Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo. Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo. Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo. Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo. Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg.
All-Cause Mortality
Part A: Placebo Part A: GSK2269577 1000 µg Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/7 (0.00%)      0/21 (0.00%)      0/5 (0.00%)      0/5 (0.00%)      0/5 (0.00%)      0/5 (0.00%)      0/6 (0.00%)      0/5 (0.00%)      0/5 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Part A: Placebo Part A: GSK2269577 1000 µg Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/7 (0.00%)      1/21 (4.76%)      0/5 (0.00%)      0/5 (0.00%)      0/5 (0.00%)      0/5 (0.00%)      0/6 (0.00%)      0/5 (0.00%)      0/5 (0.00%)    
Cardiac disorders                   
Atrial fibrillation  1  0/7 (0.00%)  1/21 (4.76%)  0/5 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/5 (0.00%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part A: Placebo Part A: GSK2269577 1000 µg Part B: Placebo Part B: GSK2269577 100 µg Part B: GSK2269577 200 µg Part B: GSK2269577 500 µg Part B: GSK2269577 700 µg Part B: GSK2269577 1000 µg Part B: GSK2269577 2000 µg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/7 (28.57%)      7/21 (33.33%)      3/5 (60.00%)      3/5 (60.00%)      2/5 (40.00%)      1/5 (20.00%)      3/6 (50.00%)      4/5 (80.00%)      2/5 (40.00%)    
Eye disorders                   
Lacrimation increased  1  0/7 (0.00%)  0/21 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0 0/5 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/5 (20.00%) 
Gastrointestinal disorders                   
Diarrhoea  1  1/7 (14.29%)  0/21 (0.00%)  0/5 (0.00%)  1/5 (20.00%)  0/5 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/5 (0.00%) 
Dry mouth  1  0/7 (0.00%)  0/21 (0.00%)  0/5 (0.00%)  1/5 (20.00%)  0/5 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/5 (0.00%) 
Toothache  1  0/7 (0.00%)  0/21 (0.00%)  1/5 (20.00%)  0/5 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/5 (0.00%) 
General disorders                   
Catheter site haematoma  1  0/7 (0.00%)  0/21 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/5 (20.00%) 
Vessel puncture site inflammation  1  0/7 (0.00%)  0/21 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/5 (20.00%) 
Infections and infestations                   
Gastroenteritis  1  1/7 (14.29%)  0/21 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/5 (0.00%) 
Nasopharyngitis  1  1/7 (14.29%)  1/21 (4.76%)  0/5 (0.00%)  0/5 (0.00%)  1/5 (20.00%)  0/5 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/5 (0.00%) 
Oral herpes  1  1/7 (14.29%)  0/21 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/5 (0.00%) 
Rhinitis  1  0/7 (0.00%)  0/21 (0.00%)  0/5 (0.00%)  1/5 (20.00%)  0/5 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/5 (20.00%) 
Sinusitis  1  0/7 (0.00%)  0/21 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  0/5 (0.00%) 
Musculoskeletal and connective tissue disorders                   
Arthralgia  1  0/7 (0.00%)  2/21 (9.52%)  0/5 (0.00%)  1/5 (20.00%)  0/5 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/5 (0.00%) 
Neck pain  1  0/7 (0.00%)  0/21 (0.00%)  1/5 (20.00%)  0/5 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/5 (0.00%) 
Pain in extremity  1  0/7 (0.00%)  0/21 (0.00%)  0/5 (0.00%)  1/5 (20.00%)  0/5 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/5 (20.00%) 
Spinal pain  1  0/7 (0.00%)  0/21 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/5 (20.00%) 
Nervous system disorders                   
Headache  1  1/7 (14.29%)  3/21 (14.29%)  1/5 (20.00%)  1/5 (20.00%)  0/5 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  1/5 (20.00%)  1/5 (20.00%) 
Dizziness  1  0/7 (0.00%)  0/21 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  0/5 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  0/5 (0.00%)  1/5 (20.00%) 
Psychiatric disorders                   
Sleep disorder  1  0/7 (0.00%)  0/21 (0.00%)  0/5 (0.00%)  1/5 (20.00%)  0/5 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/5 (0.00%) 
Respiratory, thoracic and mediastinal disorders                   
Cough  1  1/7 (14.29%)  4/21 (19.05%)  0/5 (0.00%)  0/5 (0.00%)  1/5 (20.00%)  0/5 (0.00%)  3/6 (50.00%)  4/5 (80.00%)  2/5 (40.00%) 
Oropharyngeal pain  1  0/7 (0.00%)  0/21 (0.00%)  1/5 (20.00%)  0/5 (0.00%)  0/5 (0.00%)