A Study to Evaluate the Safety, Tolerability, Pharmacokin... | NCT02130635

NCT02130635

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part A: GSK2269557 1000 MCG	Experimental	Subjects will receive 2 inhalations (2 x GSK2269557 500 mcg = total dose of 1000 mcg GSK2269557) 30 seconds apart, once daily for 14 consecutive days	Drug: GSK2269557 500 MCG
Part A: PLACEBO	Placebo Comparator	Subjects will receive 2 inhalations of placebo once daily for 14 consecutive days	Drug: PLACEBO
Part B: GSK2269557 100 MCG	Experimental	Subjects will receive 4 inhalations (1 x GSK2269557 100 mcg and 3 x Placebo = total dose of 100 mcg GSK2269557) 30 seconds apart, once daily for 14 consecutive days	Drug: GSK2269557 100 MCG Drug: PLACEBO
Part B: GSK2269557 200 MCG	Experimental	Subjects will receive 4 inhalations (2 x GSK2269557 100 mcg and 2 x Placebo = total dose of 200 mcg GSK2269557) 30 seconds apart, once daily for 14 consecutive days	Drug: GSK2269557 100 MCG Drug: PLACEBO
Part B: GSK2269557 500 MCG	Experimental	Subjects will receive 4 inhalations (1 x GSK2269557 500 mcg and 3 x Placebo = total dose of 500 mcg GSK2269557) 30 seconds apart, once daily for 14 consecutive days, once daily for 14 consecutive days

Interventions

Name	Type	Description	Arm Group Labels	Other Names
GSK2269557 100 MCG	Drug	100 mcg of GSK2269557 blended with lactose per blister administered using a dry powder inhaler device	Part B: GSK2269557 100 MCG Part B: GSK2269557 200 MCG

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Part A: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event	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.	From the start of study treatment until follow-up (assessed for approximately 19 days)
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	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.	Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Part A: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points	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.	Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 h post-dose)

Secondary Outcomes

Measure	Description	Time Frame
Part A: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose	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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

The subject has a confirmed and established diagnosis of COPD, as defined by the Global Initiative for Chronic Obstructive lung Disease (GOLD) guidelines.
Male or female of non-child bearing potential between 40 and 75 years of age inclusive, at the time of signing the informed consent.
The subject has a post-bronchodilator [400 microgram (mcg) salbutamol] Maximal amount of air FEV1/FVC <0.7 and FEV1 >=40% to <=80% of predicted (Predictions should be according to the European Community of Coal and Steel (ECCS) equations).
Subject is a smoker or an ex-smoker with a smoking history of at least 10 pack years (pack years = (cigarettes per day smoked/20) x number of years smoked)).
The subject is able to produce >100 milligram (mg) of sputum at screening.
Body weight >=45 kilogram (kg) and body mass index (BMI) within the range 17 - 32 kg/square meter (m^2) (inclusive).
A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, hysterectomy, salpingo-oophrectomy or oophrectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 milli-International units (MIU)/millilitre (mL) and estradiol < 40 picogram (pg)/mL (<147 picomole(pmol)/Liter [L]) is confirmatory]. [Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods, if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.]; or has only same-sex partners, when this is her preferred and usual lifestyle.
Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods. This criterion must be followed from the time of the first dose of study medication until the follow-up visit.
Based on averaged QTcF values of triplicate ECGs obtained over a brief recording period (e.g. 5 minutes): QTcF <450 millisecond (msec); or QTcF<480 msec in subjects with right bundle branch block.
Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included if the investigator [in consultation with the Glaxosmithkline (GSK) medical monitor if required] documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.

Exclusion Criteria:

Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome, asymptomatic gallstones and cholecystectomy).
Subjects who have a past or current medical condition or diseases that are not well controlled and, which as judged by the Investigator, may affect subject safety or influence the outcome of the study. (Note: Patients with adequately treated and well controlled concurrent medical conditions (e.g. hypertension) are permitted to be entered into the study).
Subject has a diagnosis of active tuberculosis, lung cancer, clinically overt bronchiectasis, pulmonary fibrosis, asthma or any other respiratory condition that might, in the opinion of the Investigator, compromise the safety of the subject or affect the interpretation of the results.
History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >28 units for males or >21 units for females. One unit is equivalent to 8 gram of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
History of sensitivity to any of the study medications, or components (such as lactose) thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
A positive test for Human immunodeficiency virus (HIV) antibody - tested according to local policies.
The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include cannabinoids, amphetamines, barbiturates, cocaine and opiates. The detection of drugs (e.g. benzodiazepines, opiates) taken for a legitimate medical purpose would not necessarily be an exclusion to study participation. The detection of alcohol would not be an exclusion at screening but would need to be negative pre-dose and during the study.
A positive pre-study Hepatitis B surface antigen (HBs-Ag) or positive total hepatitis B core antibody (anti-HBc IgM) or positive Hepatitis C antibody result within 3 months of screening.
Pregnant females as determined by positive urine human chorionic gonadotropin (hCG) test at screening or prior to dosing.
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
Lactating females.
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
Subject has poorly controlled or unstable COPD, defined as the occurrence of any of the following: Either: acute worsening of COPD (an exacerbation) that is managed by the subject at home requiring treatment with corticosteroids and/or antibiotics in the 4 weeks prior to the screening visit; or more than two exacerbations in the previous 2 months prior to the screening visit that required a course of oral corticosteroids and/or antibiotics, or for which the subject was hospitalised.
Subject has had a respiratory tract infection treated with antibiotics in the 4 weeks prior to first dose.
Subject requires regular treatment with oral corticosteroids or has received oral or parenteral corticosteroids within 4 weeks of screening.
Vulnerable subject (e.g., person kept in detention).
The subject is not able to understand and communicate in German or native language.

Contacts/Locations Module

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Großhansdorf	Schleswig-Holstein	22927	Germany
GSK Investigational Site

References Module

Label	URL
IPD for this study will be made available via the Clinical Study Data Request site.	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Part A: Placebo	Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
FG001	Part A: GSK2269577 1000 µg	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Part B: GSK2269557 700 MCG

FG0007 subjects
FG00121 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Part A: Placebo	Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
BG001	Part A: GSK2269577 1000 µg	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.
BG002	Part B: Placebo	Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
BG003	Part B: GSK2269577 100 µg	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.
BG004	Part B: GSK2269577 200 µg	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.
BG005	Part B: GSK2269577 500 µg	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.
BG006	Part B: GSK2269577 700 µg	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.
BG007	Part B: GSK2269577 1000 µg	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.
BG008	Part B: GSK2269577 2000 µg	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.
BG009	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Data provided for Part A

N=28

Mean

Standard Deviation

Years

Title	Denominators	Categories
	ParticipantsBG0007 ParticipantsBG00121 ParticipantsBG0020 ParticipantsBG003

Age, Continuous

Data for Part B is presented.

N=36

Mean

Standard Deviation

Years

Title	Denominators	Categories
	ParticipantsBG0000 ParticipantsBG0010 ParticipantsBG002

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG0007 ParticipantsBG00121 ParticipantsBG002

Race/Ethnicity, Customized

Number

Participants

Title	Denominators	Categories
White-White/Caucasian/European Heritage	ParticipantsBG0007 ParticipantsBG00121 ParticipantsBG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Part A: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event

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.

Safety Population: all participants who received at least one dose of study treatment.

Posted

Number

Participants

From the start of study treatment until follow-up (assessed for approximately 19 days)

ID	Title	Description
OG000	Part A: Placebo	Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
OG001	Part A: GSK2269577 1000 µg	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.

Units	Counts
Participants	OG0007 OG00121

Title

Denominators

Categories

At least one AE

Title	Measurements
	OG0002 OG0019

At least one SAE

Title	Measurements
	OG000

Primary

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

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.

Safety Population

Posted

Mean

Standard Deviation

10^9 cells per liter (GI/L)

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)

ID	Title	Description
OG000	Part A: Placebo	Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
OG001	Part A: GSK2269577 1000 µg	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.

Units	Counts
Participants

Primary

Part A: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points

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.

Safety Population

Posted

Mean

Standard Deviation

Grams/Liter (g/L)

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 h post-dose)

ID	Title	Description
OG000	Part A: Placebo	Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
OG001	Part A: GSK2269577 1000 µg	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.

Units	Counts
Participants

Primary

Part A: Change From Baseline in Hematocrit at the Indicated Time Points

Safety Population

Posted

Mean

Standard Deviation

Ratio

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)

ID	Title	Description
OG000	Part A: Placebo	Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
OG001	Part A: GSK2269577 1000 µg	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.

Units	Counts
Participants	OG000

Primary

Part A: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points

Safety Population

Posted

Mean

Standard Deviation

10^12 cells/Liter (TI/L)

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)

ID	Title	Description
OG000	Part A: Placebo	Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
OG001	Part A: GSK2269577 1000 µg	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.

Units	Counts
Participants	OG000

Primary

Part A: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points

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.

Safety Population

Posted

Mean

Standard Deviation

Picograms (pg)

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)

ID	Title	Description
OG000	Part A: Placebo	Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
OG001	Part A: GSK2269577 1000 µg	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.

Units	Counts
Participants

Primary

Part A: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points

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.

Safety Population

Posted

Mean

Standard Deviation

Femtoliters (fL)

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)

ID	Title	Description
OG000	Part A: Placebo	Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
OG001	Part A: GSK2269577 1000 µg	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.

Units	Counts
Participants

Primary

Part A: Change From Baseline in Albumin and Total Protein at the Indicated Time Points

Safety Population

Posted

Mean

Standard Deviation

g/L

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)

ID	Title	Description
OG000	Part A: Placebo	Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
OG001	Part A: GSK2269577 1000 µg	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.

Units	Counts
Participants	OG000

Primary

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

Safety Population

Posted

Mean

Standard Deviation

International Units per Liter (IU/L)

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)

ID	Title	Description
OG000	Part A: Placebo	Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
OG001	Part A: GSK2269577 1000 µg	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.

Units	Counts
Participants

Primary

Part A: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points

Safety Population

Posted

Mean

Standard Deviation

Micromoles/Liter (micromol/L)

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)

ID	Title	Description
OG000	Part A: Placebo	Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
OG001	Part A: GSK2269577 1000 µg	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.

Units	Counts
Participants

Primary

Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points

Safety Population

Posted

Mean

Standard Deviation

Millimoles per Liter (mmol/L)

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)

ID	Title	Description
OG000	Part A: Placebo	Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
OG001	Part A: GSK2269577 1000 µg	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.

Units	Counts
Participants

Primary

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

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.

Safety Population

Posted

Number

Participants

Day 1, Day 7, and Day 14

ID	Title	Description
OG000	Part A: Placebo	Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
OG001	Part A: GSK2269577 1000 µg	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.

Units	Counts

Primary

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

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.

Safety Population

Posted

Number

Participants

Day 1, Day 7, and Day 14

ID	Title	Description
OG000	Part A: Placebo	Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
OG001	Part A: GSK2269577 1000 µg	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.

Units	Counts
Participants

Primary

Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points

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.

Safety Population

Posted

Mean

95% Confidence Interval

Liters

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)

ID	Title	Description
OG000	Part A: Placebo	Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.
OG001	Part A: GSK2269577 1000 µg	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.

Primary

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

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.

Safety Population

Posted

Median

95% Confidence Interval

Picograms/milliliter (pg/mL)

Day 7 (pre-dose) and Day 14 (24 h post-dose)

ID	Title	Description
OG000	Part B: Placebo	Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
OG001	Part B: GSK2269577 100 µg	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.

Secondary

Part A: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose

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.

PK Population: participants in the Safety Population for whom a PK sample was obtained and analyzed.

Posted

Geometric Mean

95% Confidence Interval

pg/mL

Day 1 (Pre-dose, 5 min, 30 min, 1, 2, 4 & 6 hours post-dose)

ID	Title	Description
OG000	Part A: GSK2269577 1000 µg	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.

Units	Counts
Participants	OG000

Secondary

Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose

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.

PK Population

Posted

Geometric Mean

95% Confidence Interval

pg/mL

Pre-dose, and 5 min, 30 min, 1 h, 2 h, 4 h, and 6 h post-dose on Day 1

ID	Title	Description
OG000	Part B: GSK2269577 100 µg	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.
OG001	Part B: GSK2269577 200 µg	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.
OG002	Part B: GSK2269577 500 µg

Secondary

Part A: Maximum Observed Plasma Concentration (Cmax) of GSK2269577 on Day 7

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.

PK Population

Posted

Geometric Mean

95% Confidence Interval

pg/mL

Day 7 immediately after dosing

ID	Title	Description
OG000	Part A: GSK2269577 1000 µg	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.

Units	Counts
Participants	OG000

Secondary

Part B: Maximum Observed Plasma Concentration (Cmax) of GSK2269577 on Day 7

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.

PK Population

Posted

Geometric Mean

95% Confidence Interval

pg/mL

Day 7 immediately after dosing

ID	Title	Description
OG000	Part B: GSK2269577 100 µg	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.
OG001	Part B: GSK2269577 200 µg	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.
OG002	Part B: GSK2269577 500 µg	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.

Secondary

Part A: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15

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.

PK Population

Posted

Geometric Mean

95% Confidence Interval

pg/mL

Day 7 and Day 15

ID	Title	Description
OG000	Part A: GSK2269577 1000 µg	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.

Units	Counts
Participants	OG000

Secondary

Part B: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15

PK Population

Posted

Geometric Mean

95% Confidence Interval

pg/mL

Day 7 and Day 15

ID	Title	Description
OG000	Part B: GSK2269577 100 µg	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.
OG001	Part B: GSK2269577 200 µg	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.
OG002	Part B: GSK2269577 500 µg	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.

Secondary

Part B: Number of Times Rescue Medication Was Used by Participants Daily, During the Treatment Period

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.

Safety Population

Posted

Mean

Standard Deviation

Number of times

Day 1 to Day 15

ID	Title	Description
OG000	Part B: Placebo	Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
OG001	Part B: GSK2269577 100 µg	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.
OG002	Part B: GSK2269577 200 µg	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.

Secondary

Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event

Safety Population

Posted

Number

Participants

From the start of study treatment until follow-up (assessed for approximately 19 days)

ID	Title	Description
OG000	Part B: Placebo	Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
OG001	Part B: GSK2269577 100 µg	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.

Secondary

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

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.

Safety Population

Posted

Mean

Standard Deviation

10^9 cells per liter (GI/L)

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)

ID	Title	Description
OG000	Part B: Placebo	Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
OG001	Part B: GSK2269577 100 µg	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.
OG002	Part B: GSK2269577 200 µg	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.

Secondary

Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points

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.

Safety Population

Posted

Mean

Standard Deviation

g/L

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)

ID	Title	Description
OG000	Part B: Placebo	Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
OG001	Part B: GSK2269577 100 µg	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.
OG002	Part B: GSK2269577 200 µg	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.

Secondary

Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points

Safety Population

Posted

Mean

Standard Deviation

10^12 cells/Liter (TI/L)

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)

ID	Title	Description
OG000	Part B: Placebo	Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
OG001	Part B: GSK2269577 100 µg	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.
OG002	Part B: GSK2269577 200 µg	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.

Secondary

Part B: Change From Baseline in Hematocrit at the Indicated Time Points

Safety Population

Posted

Mean

Standard Deviation

Ratio

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)

ID	Title	Description
OG000	Part B: Placebo	Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
OG001	Part B: GSK2269577 100 µg	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.
OG002	Part B: GSK2269577 200 µg	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.

Secondary

Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points

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.

Safety Population

Posted

Mean

Standard Deviation

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)

ID	Title	Description
OG000	Part B: Placebo	Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
OG001	Part B: GSK2269577 100 µg	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.
OG002	Part B: GSK2269577 200 µg	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.

Secondary

Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points

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.

Safety Population

Posted

Mean

Standard Deviation

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)

ID	Title	Description
OG000	Part B: Placebo	Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
OG001	Part B: GSK2269577 100 µg	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.
OG002	Part B: GSK2269577 200 µg	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.

Secondary

Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points

Safety Population

Posted

Mean

Standard Deviation

g/L

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)

ID	Title	Description
OG000	Part B: Placebo	Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
OG001	Part B: GSK2269577 100 µg	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.
OG002	Part B: GSK2269577 200 µg	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.

Secondary

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

Safety Population

Posted

Mean

Standard Deviation

International Units per Liter (IU/L)

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)

ID	Title	Description
OG000	Part B: Placebo	Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
OG001	Part B: GSK2269577 100 µg	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.
OG002	Part B: GSK2269577 200 µg	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.

Secondary

Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points

Safety Population

Posted

Mean

Standard Deviation

Micromoles/Liter (micromol/L)

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)

ID	Title	Description
OG000	Part B: Placebo	Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
OG001	Part B: GSK2269577 100 µg	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.
OG002	Part B: GSK2269577 200 µg	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.

Secondary

Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points

Safety Population

Posted

Mean

Standard Deviation

Millimoles per Liter (mmol/L)

Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)

ID	Title	Description
OG000	Part B: Placebo	Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
OG001	Part B: GSK2269577 100 µg	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.
OG002	Part B: GSK2269577 200 µg	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.

Secondary

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

Safety Population

Posted

Number

Participants

Day 1, Day 7, and Day 14

ID	Title	Description
OG000	Part B: Placebo	Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
OG001	Part B: GSK2269577 100 µg	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.
OG002	Part B: GSK2269577 200 µg	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.

Secondary

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

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.

Safety Population

Posted

Number

Participants

Day 1, Day 7, and Day 14

ID	Title	Description
OG000	Part B: Placebo	Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
OG001	Part B: GSK2269577 100 µg	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.
OG002	Part B: GSK2269577 200 µg	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.

Secondary

Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up

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.

Safety Population

Posted

Mean

95% Confidence Interval

Liters

Screening (up to 30 days prior to Day 1) and Follow-up (approximately Day 19)

ID	Title	Description
OG000	Part B: Placebo	Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.
OG001	Part B: GSK2269577 100 µg	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.
OG002	Part B: GSK2269577 200 µg

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part A: Placebo	Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.	7	0	7	2	7
EG001	Part A: GSK2269577 1000 µg	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.	21	1	21	7	21
EG002	Part B: Placebo	Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.	5	0	5	3	5
EG003	Part B: GSK2269577 100 µg	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.	5	0	5	3	5
EG004	Part B: GSK2269577 200 µg	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.	5	0	5	2	5
EG005	Part B: GSK2269577 500 µg	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.	5	0	5	1	5
EG006	Part B: GSK2269577 700 µg	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.	6	0	6	3	6
EG007	Part B: GSK2269577 1000 µg	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.	5	0	5	4	5
EG008	Part B: GSK2269577 2000 µg	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.	5	0	5	2	5

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment		EG0000 affected7 at risk EG0011 affected21 at risk EG0020 affected5 at risk EG0030 affected5 at risk EG0040 affected5 at risk EG0050 affected5 at risk EG0060 affected6 at risk EG0070 affected5 at risk EG0080 affected5 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected7 at risk EG0010 affected21 at risk EG0020 affected5 at risk EG0031 affected5 at risk EG0040 affected5 at risk EG0050 affected5 at risk EG0060 affected6 at risk EG0070 affected5 at risk EG0080 affected5 at risk
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected7 at risk EG0010 affected21 at risk EG0020 affected5 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected7 at risk EG0011 affected21 at risk EG0020 affected5 at risk EG003
Oral herpes	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected7 at risk EG0010 affected21 at risk EG0020 affected5 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected7 at risk EG0012 affected21 at risk EG0020 affected5 at risk EG003
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected7 at risk EG0013 affected21 at risk EG0021 affected5 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected7 at risk EG0014 affected21 at risk EG0020 affected5 at risk EG003
Lacrimation increased	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected7 at risk EG0010 affected21 at risk EG0020 affected5 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected7 at risk EG0010 affected21 at risk EG0020 affected5 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected7 at risk EG0010 affected21 at risk EG0021 affected5 at risk EG003
Catheter site haematoma	General disorders	MedDRA	Systematic Assessment	EG0000 affected7 at risk EG0010 affected21 at risk EG0020 affected5 at risk EG003
Vessel puncture site inflammation	General disorders	MedDRA	Systematic Assessment	EG0000 affected7 at risk EG0010 affected21 at risk EG0020 affected5 at risk EG003
Rhinitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected7 at risk EG0010 affected21 at risk EG0020 affected5 at risk EG003
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected7 at risk EG0010 affected21 at risk EG0020 affected5 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected7 at risk EG0010 affected21 at risk EG0021 affected5 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected7 at risk EG0010 affected21 at risk EG0020 affected5 at risk EG003
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected7 at risk EG0010 affected21 at risk EG0020 affected5 at risk EG003
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected7 at risk EG0010 affected21 at risk EG0020 affected5 at risk EG003
Sleep disorder	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected7 at risk EG0010 affected21 at risk EG0020 affected5 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected7 at risk EG0010 affected21 at risk EG0021 affected5 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected7 at risk EG0010 affected21 at risk EG0021 affected5 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected7 at risk EG0010 affected21 at risk EG0021 affected5 at risk EG003

ID	Term
D029424	Pulmonary Disease, Chronic Obstructive

Ancestor Terms

ID	Term
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
C000629641	Nemiralisib

Units	Counts
Participants	OG0007 OG00121

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.

EG0040 affected5 at risk

EG0050 affected5 at risk

EG0060 affected6 at risk

EG0070 affected5 at risk

EG0080 affected5 at risk

EG0041 affected5 at risk

EG0050 affected5 at risk

EG0060 affected6 at risk

EG0070 affected5 at risk

EG0080 affected5 at risk

EG0040 affected5 at risk

EG0050 affected5 at risk

EG0060 affected6 at risk

EG0070 affected5 at risk

EG0080 affected5 at risk

EG0040 affected5 at risk

EG0050 affected5 at risk

EG0060 affected6 at risk

EG0070 affected5 at risk

EG0080 affected5 at risk

EG0040 affected5 at risk

EG0050 affected5 at risk

EG0061 affected6 at risk

EG0071 affected5 at risk

EG0081 affected5 at risk

EG0041 affected5 at risk

EG0050 affected5 at risk

EG0063 affected6 at risk

EG0074 affected5 at risk

EG0082 affected5 at risk

EG0040 events0 affected5 at risk

EG0050 affected5 at risk

EG0060 affected6 at risk

EG0070 affected5 at risk

EG0081 affected5 at risk

EG0040 affected5 at risk

EG0050 affected5 at risk

EG0060 affected6 at risk

EG0070 affected5 at risk

EG0080 affected5 at risk

EG0040 affected5 at risk

EG0050 affected5 at risk

EG0060 affected6 at risk

EG0070 affected5 at risk

EG0080 affected5 at risk

EG0040 affected5 at risk

EG0050 affected5 at risk

EG0060 affected6 at risk

EG0070 affected5 at risk

EG0081 affected5 at risk

EG0040 affected5 at risk

EG0050 affected5 at risk

EG0060 affected6 at risk

EG0070 affected5 at risk

EG0081 affected5 at risk

EG0040 affected5 at risk

EG0050 affected5 at risk

EG0060 affected6 at risk

EG0071 affected5 at risk

EG0081 affected5 at risk

EG0040 affected5 at risk

EG0050 affected5 at risk

EG0061 affected6 at risk

EG0070 affected5 at risk

EG0080 affected5 at risk

EG0040 affected5 at risk

EG0050 affected5 at risk

EG0060 affected6 at risk

EG0070 affected5 at risk

EG0080 affected5 at risk

EG0040 affected5 at risk

EG0050 affected5 at risk

EG0060 affected6 at risk

EG0070 affected5 at risk

EG0081 affected5 at risk

EG0040 affected5 at risk

EG0050 affected5 at risk

EG0060 affected6 at risk

EG0070 affected5 at risk

EG0081 affected5 at risk

EG0040 affected5 at risk

EG0051 affected5 at risk

EG0060 affected6 at risk

EG0070 affected5 at risk

EG0081 affected5 at risk

EG0040 affected5 at risk

EG0050 affected5 at risk

EG0060 affected6 at risk

EG0070 affected5 at risk

EG0080 affected5 at risk

EG0040 affected5 at risk

EG0050 affected5 at risk

EG0060 affected6 at risk

EG0070 affected5 at risk

EG0080 affected5 at risk

EG0040 affected5 at risk

EG0050 affected5 at risk

EG0060 affected6 at risk

EG0070 affected5 at risk

EG0080 affected5 at risk

EG0040 affected5 at risk

EG0050 affected5 at risk

EG0060 affected6 at risk

EG0070 affected5 at risk

EG0080 affected5 at risk

OG00435.19(18.32 to 66.93)

OG00542.56(20.57 to 90.25)

OG00641.52(20.62 to 82.81)

OG0042650.13(1535.07 to 4634.07)

OG0052636.08(1412.65 to 4978.59)

OG0062279.48(1205.35 to 4210.75)

OG0041356.35(696.37 to 2645.82)

OG0052394.65(1125.17 to 5196.20)

OG0062170.41(1010.85 to 4582.03)

OG0047.32(3.02 to 17.85)

OG0053.68(1.26 to 10.51)

OG0062.62(0.94 to 7.15)

OG0043.99(1.86 to 8.50)

OG0053.00(1.34 to 6.75)

OG0061.53(0.66 to 3.47)

OG004853.4(380.2 to 1915.6)

OG005982.9(311.1 to 3105.3)

OG004556.9(384.8 to 806.0)

OG0051011.6(757.1 to 1351.6)

OG004599.7(370.5 to 970.7)

OG0051203.3(799.1 to 1812.0)

OG004672.3(434.0 to 1041.5)

OG0051402(892.8 to 2201.4)

OG004468.7(305.5 to 719.2)

OG0051098.5(781.9 to 1543.2)

OG004466.5(273.1 to 796.6)

OG005900.8(723.8 to 1121.0)

OG0041218.5(985.88 to 1506.01)

OG0051767.34(1079.72 to 2892.86)

OG005-0.008± 0.0189

OG005-0.002± 0.0287

OG005-0.118± 0.3223

OG006-0.218± 0.6236

OG005-0.243± 0.3054

OG006-0.802± 0.7889

OG006-1.012± 1.3388

OG004-0.083± 0.0958

OG006-0.084± 0.1496

OG0040.00397± 0.008856

OG0050.00882± 0.018576

OG0060.01792± 0.012824