An Efficacy Study of GSK2269557 Added to Standard Care in... | NCT02294734

ID	Type	Description	Link
2014-001972-70	EudraCT Number

Label	Type	Description	Intervention Names
GSK2269557 repeat dose	Experimental	Participants will receive 2 inhalation of GSK2269557 dry powder once daily via DISKUS™ 'device' (DISKUS is a trademark of the GSK group of companies)	Drug: GSK2269557
Matching placebo repeat dose	Placebo Comparator	Participants will receive 2 inhalation matching placebo dry powder once daily via DISKUS 'device'	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
GSK2269557	Drug	Dry powder for inhalation via DISKUS 'device' with unit dose strength of 500 micrograms (mcg) per actuation with total dose of 1000 mcg daily	GSK2269557 repeat dose

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Specific Imaging Airway Volume (siVaw), Measured at FRC and TLC Scan Conditions, Presented in Longitudinal and Scan Trimmed Scan Types, Measured in 5 Lobes and 5 Regions at Screening, Day 12 and Day 28	siVaw is a measure of the volume in an individual's airway corrected for their lobar volume derived from the high resolution computed tomography (HRCT). It was measured at functional residual volume (FRC) and total lung capacity (TLC). Data was collected at longitudinal time points: Screening, Day 12 & Day 28 and at each time point for scan trimmed pairs: SCRD12, SCRD28 & D12D28. At each time point it was measure at 5 lobes (RUL, LUL, RML, RLL & LLL) and 5 Regions (Upper, Lower, Central, Distal & Total). For longitudinal time points and SCRD12 & SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only particpants available at the specified time point were analysed (represented by n=X1, X2 in the category title).	Baseline, Day 12 and Day 28

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Imaging Airways Volume: iVaw, Measured at FRC and TLC Scan Conditions, Presented in Longitudinal and Scan Trimmed Scan Types, Measured in 5 Lobes and 5 Regions at Screening, Day 12 and Day 28	iVaw was derived from HRCT to evaluate the effect of once daily inhaled dose of GSK2269557 on lung parameters. Data was collected at longitudinal time points: Screening, Day 12 & Day 28 and at each time point for scan trimmed pairs: SCRD12, SCRD28 & D12D28. At each time point it was measure at 5 lobes (RUL, LUL, RML, RLL & LLL) and 5 Regions (Upper, Lower, Central, Distal & Total). For longitudinal time points and SCRD12 & SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only particpants available at the specified time point were analysed (represented by n=X1, X2 in the category title).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Between 40 and 80 years of age inclusive, at the time of signing the informed consent
The subject has a confirmed and established diagnosis of COPD, as defined by the global initiative for chronic Obstructive Lung Disease (GOLD) guidelines for at least 6 months prior to entry.
The subject has a post-bronchodilator FEV1/Forced Vital Capacity (FVC) < 0.7 and FEV1 <= 80 % of predicted (Predictions should be according to the European Community of Coal and Steel [ECCS] equations), documented in the last 5 years.
Disease severity: Acute exacerbation of COPD requiring an escalation in therapy to include corticosteroid and antibiotics. Acute exacerbation to be confirmed by an experienced physician and represent a recent change in at least two major and one minor symptoms, one major and two minor symptoms, or all 3 major symptoms. Major symptoms: subjective increase in dyspnea, increase in sputum volume, and change in sputum colour. Minor symptoms: cough, wheeze and sore throat.
The 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])
Body weight >= 45 kilogram (kg) and body mass index (BMI) within the range 18 - 32 kg/metered squared (m^2) (inclusive).
Male
Female subject : is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the following conditions applies:

Non-reproductive potential defined as: Pre-menopausal females with one of the following: documented tubal ligation, documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, hysterectomy and documented bilateral oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone [FSH] and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective 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.

Reproductive potential and agrees to follow one of the options listed below in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication and until completion of the follow-up visit.

GlaxoSmithKline (GSK) Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP):

Contraceptive subdermal implant that meets the standard operating procedure (SOP) effectiveness criteria including a <1% rate of failure per year, as stated in the product label.

Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a <1% rate of failure per year, as stated in the product label.

Oral Contraceptive, either combined or progestogen alone. Injectable progestogen. Contraceptive vaginal ring. Percutaneous contraceptive patches. Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject.

Male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository).

Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until after the completion of the follow up visit.

Vasectomy with documentation of azoospermia. Male condom plus partner use of one of the contraceptive options below: Contraceptive subdermal implant that meets the SOP effectiveness criteria including a <1% rate of failure per year, as stated in the product label. Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a <1% rate of failure per year, as stated in the product label. Oral Contraceptive, either combined or progestogen alone or injectable progestogen. Contraceptive vaginal ring. Percutaneous contraceptive patches.

These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.

Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in the study protocol.

Exclusion Criteria:

To avoid recruitment of subjects with a severe COPD exacerbation, the presence of any one of the following severity criteria will render the subject ineligible for inclusion in the study:

Need for invasive mechanical ventilation (short term (< 48hour) Non-invasive Ventilation (NIV) or Continuous Positive Airway Pressure [CPAP] is acceptable).

Haemodynamic instability or clinically significant heart failure. Confusion.

Subjects who have a history or current medical conditions 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 or non-insulin dependent diabetes mellitus] 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.
Alanine aminotransferase >2x upper limit of normal (ULN) and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the exclusion criteria, outside of the reference range for the population being studied may be included if the Investigator [in consultation with the GSK Medical Monitor if required] documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
ECG indicative of an acute cardiac event (e.g. Myocardial Infarction) or demonstrating a clinically significant arrhythmia requiring treatment.
QTcF > 450 millisecond (msec) or QTcF > 480 msec in subjects with Bundle Branch Block, based on single QTcF value.
Subjects who have undergone lung volume reduction surgery.
Subject is currently on chronic treatment with macrolides; long term oxygen therapy (> 15 hours/day).
The subject has been on chronic treatment with anti-Tumour Necrosis Factor (anti-TNF), anti-Interleukin-1 (anti-IL1), or any other immunosuppressive therapy within 60 days prior to dosing.
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 ( equivalent to 240 milliliter [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 thereof (such as lactose) or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
A known (historical) positive test for human immune virus (HIV) antibody.
Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. NOTE: Because of the short window for screening, treatment with GSK2269557 may start before receiving the result of the hepatitis tests. If subsequently the test is found to be positive, the subject may be withdrawn, as judged by the Principal Investigator in consultation with the Medical Monitor.
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.
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 4 investigational medicinal products within 12 months prior to the first dosing day.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Edegem		2650	Belgium
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
34113093	Background	Cahn A, Hamblin JN, Robertson J, Begg M, Jarvis E, Wilson R, Dear G, Leemereise C, Cui Y, Mizuma M, Montembault M, Van Holsbeke C, Vos W, De Backer W, De Backer J, Hessel EM. An Inhaled PI3Kdelta Inhibitor Improves Recovery in Acutely Exacerbating COPD Patients: A Randomized Trial. Int J Chron Obstruct Pulmon Dis. 2021 Jun 3;16:1607-1619. doi: 10.2147/COPD.S309129. eCollection 2021.

ID	Title	Description
FG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
FG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

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

Change From Baseline in Specific Imaging Airway Volume (siVaw), Measured at FRC and TLC Scan Conditions, Presented in Longitudinal and Scan Trimmed Scan Types, Measured in 5 Lobes and 5 Regions at Screening, Day 12 and Day 28

siVaw is a measure of the volume in an individual's airway corrected for their lobar volume derived from the high resolution computed tomography (HRCT). It was measured at functional residual volume (FRC) and total lung capacity (TLC). Data was collected at longitudinal time points: Screening, Day 12 & Day 28 and at each time point for scan trimmed pairs: SCRD12, SCRD28 & D12D28. At each time point it was measure at 5 lobes (RUL, LUL, RML, RLL & LLL) and 5 Regions (Upper, Lower, Central, Distal & Total). For longitudinal time points and SCRD12 & SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only particpants available at the specified time point were analysed (represented by n=X1, X2 in the category title).

Intention to Treat (ITT) Population excluding the subject with a pacemaker.

Posted

Geometric Mean

95% Confidence Interval

Milliliter/Liter (mL/L)

Baseline, Day 12 and Day 28

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Units	Counts
Participants	OG00062 OG00163

Title

Denominators

Categories

FRC; Longitudinal; Lobes; RUL; D12 , n =54, 57

Title	Measurements
	OG0001.033(0.851 to 1.255) OG0011.052(0.924 to 1.197)

FRC; Longitudinal; Lobes; RUL; D28 , n =56, 56

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Bayesian repeated measures model	Non-informative priors used for all modelling parameters. Unstructured covariance matrix fitted, accounting for correlation within region and visit.	60.66	The data entered for the p-value represents the posterior probability that the true treatment ratio is greater than 1. P-value is denoted in percentage.	Posterior Median Ratio	1.03			2-Sided	95	0.85	1.25			FRC; Longitudinal; Lobes; RUL; D12. The data entered to the 95% confidence interval represents the 95% equi-tailed credible interval.		Superiority or Other (legacy)

Secondary

Change From Baseline in Imaging Airways Volume: iVaw, Measured at FRC and TLC Scan Conditions, Presented in Longitudinal and Scan Trimmed Scan Types, Measured in 5 Lobes and 5 Regions at Screening, Day 12 and Day 28

iVaw was derived from HRCT to evaluate the effect of once daily inhaled dose of GSK2269557 on lung parameters. Data was collected at longitudinal time points: Screening, Day 12 & Day 28 and at each time point for scan trimmed pairs: SCRD12, SCRD28 & D12D28. At each time point it was measure at 5 lobes (RUL, LUL, RML, RLL & LLL) and 5 Regions (Upper, Lower, Central, Distal & Total). For longitudinal time points and SCRD12 & SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only particpants available at the specified time point were analysed (represented by n=X1, X2 in the category title).

ITT Population excluding the subject with a pacemaker.

Posted

Geometric Mean

95% Confidence Interval

Milliliter (mL)

Baseline, Day 12 and Day 28

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Secondary

Change From Baseline in Imaging Airways Resistance ( iRaw) Measured at FRC and TLC Scan Conditions, Presented in Scan Trimmed Scan Types, Measured in 5 Lobes and 5 Regions at Screening, Day 12 and Day 28

iRaw was derived from HRCT to evaluate the effect of once daily inhaled dose of GSK2269557 on lung parameters. It was measured at functional residual volume (FRC) and total lung capacity (TLC). Data was collected at each time point for scan trimmed pairs: SCRD12, SCRD28 & D12D28. At each time point it was measure at 5 lobes (RUL, LUL, RML, RLL & LLL) and 5 Regions (Upper, Lower, Central, Distal & Total). For SCRD12 & SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only particpants available at the specified time point were analysed (represented by n=X1, X2 in the category title).

ITT Population excluding the subject with a pacemaker.

Posted

Geometric Mean

95% Confidence Interval

Kilopascal (Kpa)*s/L

Baseline, Day 12 and Day 28

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Secondary

Change From Baseline in Imaging Specific Airways Resistance: siRaw Measured at FRC and TLC Scan Conditions, Presented in Scan Trimmed Scan Types, Measured in 5 Lobes and 5 Regions at Screening, Day 12 and Day 28

siRaw was derived from HRCT to evaluate the effect of once daily inhaled dose of GSK2269557 on lung parameters. It was measured at functional residual volume (FRC) and total lung capacity (TLC). Data was collected at each time point for scan trimmed pairs: SCRD12, SCRD28 & D12D28. At each time point it was measure at 5 lobes (RUL, LUL, RML, RLL & LLL) and 5 Regions (Upper, Lower, Central, Distal & Total). For SCRD12 & SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only particpants available at the specified time point were analysed (represented by n=X1, X2 in the category title).

ITT Population excluding the subject with a pacemaker.

Posted

Geometric Mean

95% Confidence Interval

Kpa*s

Baseline, Day 12 and Day 28

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Secondary

Change From Baseline in Lung Lobar Volumes Measured at FRC and TLC Scan Conditions, Presented in Longitudinal Scan Types, Measured in 5 Lobes and 5 Regions at Day 12 and Day 28

Change from Baseline in lung lobar volumes was measured at functional residual volume (FRC) and total lung capacity (TLC) scan conditions. Data was collected at longitudinal time points: Day 12 & Day 28. At each time point it was measure at 5 lobes (RUL, LUL, RML, RLL & LLL) and 5 Regions (Upper, Lower, Central, Distal & Total). For longitudinal time points the baseline is screening. Change from baseline is the post-Baseline value minus the Baseline value. Only particpants available at the specified time point were analysed (represented by n=X1, X2 in the category title).

ITT Population excluding the subject with a pacemaker.

Posted

Geometric Mean

95% Confidence Interval

Baseline, Day 12 and Day 28

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Secondary

Change From Baseline in Imaging Trachea Length and Diameter After 12 Days of Treatment and After 28 Days of Treatment

Imaging trachea length and diameter was derived from HRCT to evaluate the effect of once daily inhaled dose of GSK2269557 on lung parameters. TLC is the volume in the lungs at maximal inflation and FRC is the volume in the lungs at the end-expiratory position. The Baseline for the assessment on Day 12 and Day 28 is the Screening value. Change from Baseline is the post-Baseline value minus the Baseline value. The change from Baseline data is presented for Day 12 and Day 28 for trachea length and diameter. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

ITT Population excluding the subject with a pacemaker.

Posted

Mean

Standard Deviation

Millimeter (mm)

Baseline, Day 12 and Day 28

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Secondary

Change From Baseline in Imaging Trachea Length/Diameter After 12 Days of Treatment and After 28 Days of Treatment

Imaging trachea length/diameter was derived from HRCT to evaluate the effect of once daily inhaled dose of GSK2269557 on lung parameters. TLC is the volume in the lungs at maximal inflation and FRC is the volume in the lungs at the end-expiratory position. The Baseline for the assessment on Day 12 and Day 28 is the Screening value. Change from Baseline is the post-Baseline value minus the Baseline value. The change from Baseline data is presented for Day 12 and Day 28 for trachea length/diameter. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

ITT Population excluding the subject with a pacemaker.

Posted

Mean

Standard Deviation

ratio

Baseline, Day 12 and Day 28

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 µg	Participants received 1000 µg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Units

Secondary

Number of Participants With Adverse Events (AE)

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. Adverse events were collected from the start of study treatment until the follow-up contact.

All Subjects Population: all randomized participants who received at least one dose of study treatment.

Posted

Number

Participants

From start of IP through the Study Phase (84 days post-dose) (assessed up to follow-up duration of approximately 100 days)

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Units	Counts
Participants

Secondary

Number of Participants With Abnormal Hematology Parameters

Hematology parameter included Hematocrit (HCT), Hemoglobin (HB), Lymphocytes (LC), Platelet Count (PC), Total Neutrophils (TN), and White Blood Cell (WBC) count at the indicated timepoints: Day 1, Day 12, Day 28, Day 56, Day 84, and at follow-up/Early withdrawal. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

All Subjects Population

Posted

Number

Participants

Day 1, Day 12, Day 28, Day 56, Day 84 and at follow-up (approximately 100 Days)

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Units	Counts
Participants

Secondary

Number of Participants With Abnormal Clinical Chemistry Parameters

Clinical Chemistry parameters included Alanine Amino Transferase (ALT), Albumin, Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Calcium (Ca), Glucose, Potassium (K), Sodium (Na), and Total Bilirubin (TBL) at the indicated timepoints: Day 1, Day 12, Day 28, Day 56, Day 84, and at follow-up/Early withdrawal. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

All Subject Population

Posted

Number

Participants

Day 1, Day 12, Day 28, Day 56, Day 84 and at follow-up (approximately 100 days)

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Units	Counts
Participants

Secondary

Number of Participants With Abnormal Vital Signs

Vital signs included high and low diastolic and systolic blood presure (BP), and high and low heart rate (HR). Vital signs outside the range of potential clinical importance are presented at the indicated timepoints: Day 1, Day 12, Day 28, Day 56, Day 84, follow-up/Early withdrawal and at any visit post-baseline . Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

All Subject Population

Posted

Number

Participants

Day 1, Day 12, Day 28, Day 56, Day 84 and at follow-up (approximately 100 days)

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Units	Counts
Participants

Secondary

Number of Participants With Abnormal 12-lead Electrocardiogram (ECG)

12-lead ECG was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF). Clinically non-significant (CN) and Clinically significant (CS) abnormal ECG measurements are presented for Day 1, Day 12, Day 28, Day 56, Day 84, follow-up/Early withdrawal and at any visit post-baseline. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

All Subject Population

Posted

Number

Participants

Day 1, Day 12, Day 28, Day 56, Day 84 and at follow-up (approximately 100 days)

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Units	Counts
Participants

Secondary

Day 1 Plasma Concentration up to 24 Hours (Hrs) Post-dose

Plasma samples were collected at pre-dose, 5 minutes (min), 3 hrs, and 24 hrs post-dose on Day 1. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Pharmacokinetic (PK) Population: all participants in the Safety Population for whom a PK sample was obtained and analyzed. Safety Population comprises of all participants who were randomized.

Pharmacokinetic (PK) Population

Posted

Mean

Standard Deviation

pg/mL

Pre-dose, 5 min, 3 hrs and 24 hrs

ID	Title	Description
OG000	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Units	Counts
Participants	OG000

Secondary

Trough Concentration After 12 Days, 28 Days, 56 Days and 84 Days of Treatment

Trough concentrations are presented for Pre-dose Day 12, Pre-dose Day 28, Pre-dose Day 56, and Pre-dose Day 84. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

PK Population

Posted

Mean

Standard Deviation

pg/mL

Pre-dose Day 12, Day 28, Day 56, and Day 84

ID	Title	Description
OG000	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Units	Counts
Participants	OG000

Secondary

Changes From Baseline in Forced Expiratory Volume in One Second (FEV1) Measured Daily

FEV1 is the volume of air that can forcibly be blown out in one second. A triplicate FEV1 measurement were taken daily in the morning before dose administration. Baseline is defined as the assessment on Day 1 and change from Baseline is the post-Baseline value minus Baseline value. Change from Baseline data is presented for Day 28 and Day 84.Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

ITT Population

Posted

Mean

Standard Deviation

Baseline, Day 28, and Day 84

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Units	Counts
Participants

Secondary

Changes From Baseline in Peak Expiratory Flow (PEF) Measured Daily

PEF is the maximal flow (or speed) achieved during the maximally forced expiration initiated at full inspiration. Baseline is defined as the assessment on Day 1 and change from Baseline is the post-Baseline value minus Baseline value. Change from Baseline data is presented for Day 28 and Day 84.Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

ITT Population

Posted

Mean

Standard Deviation

L/min

Baseline, Day 28, and Day 84

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Diffusion Capacity (DLco, Kco) After 28 Days and After 84 Days of Treatment

DLco is diffusing capacity o f the lungs for carbon monoxide and is defined as the extent to which oxygen passes from the air sacs of the lungs into the blood. KCO is the carbon monoxide transfer coefficient. It is an index of the efficiency of alveolar transfer of carbon monoxide. Baseline is defined as the assessment on Day 2 and percent change from Baseline is the post-Baseline value minus Baseline value/100. Change from Baseline data is presented for Day 28 and Day 84. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

ITT Population

Posted

Mean

Standard Deviation

Percent

Baseline, Day 28 and Day 84

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Units	Counts

Secondary

Change From Baseline in Total Lung Capacity (TLC) After 28 Days and After 84 Days of Treatment

TLC is the maximum amount of air that can fill the lungs. Baseline is defined as the assessment on Day 2 and change from Baseline is the post-Baseline value minus Baseline value. Change from Baseline data is presented for Day 28 and Day 84. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Note: values mentioned as 95% confidence interval below are in fact values of 95% credible interval.

ITT Population

Posted

Median

95% Confidence Interval

Baseline, Day 28 and Day 84

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Units	Counts
Participants

Secondary

Change From Baseline in Residual Volume After 28 Days and After 84 Days of Treatment

Residual volume is a lung volume representing the amount of air left in the lungs after a forced exhalation. Baseline is defined as the assessment on Day 2 and change from Baseline is the post-Baseline value minus Baseline value. Change from Baseline data is presented for Day 28 and Day 84. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Note: values mentioned as 95% confidence interval below are in fact values of 95% credible interval.

ITT Population

Posted

Median

95% Confidence Interval

Baseline, Day 28 and Day 84

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Units	Counts
Participants

Secondary

Change From Baseline in Functional Residual Capacity After 28 Days and After 84 Days of Treatment

Functional residual capacity is the volume of air present in the lungs at the end of passive expiration. Baseline is defined as the assessment on Day 2 and change from Baseline is the post-Baseline value minus Baseline value. Change from Baseline data is presented for Day 28 and Day 84. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

ITT Population

Posted

Mean

Standard Deviation

Baseline, Day 28 and Day 84

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Units	Counts
Participants

Secondary

Change From Baseline in Specific Resistance (sRaw) After 28 Days and After 84 Days of Treatment

sRaw is the measure of specific resistance. Baseline is defined as the assessment on Day 2 and change from Baseline is the post-Baseline value minus Baseline value. Change from Baseline data is presented for Day 28 and Day 84. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

ITT Population

Posted

Mean

Standard Deviation

KPa*s

Baseline, Day 28 and Day 84

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Specific Conductance (sGaw) After 28 Days and After 84 Days of Treatment

Baseline is defined as the assessment on Day 2 and change from Baseline is the post-Baseline value minus Baseline value. Change from Baseline data is presented for Day 28 and Day 84. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).Note: values mentioned as 95% confidence interval below are in fact values of 95% Credible Interval.

ITT Population

Posted

Median

95% Confidence Interval

1/KPA*S

Baseline, Day 28 and Day 84

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Units	Counts
Participants

Secondary

Questionnaires CAT and MMRC Scale at Baseline, Day 28 and Day 84

The chronic obstructive pulmonary disease (COPD) assessement test (CAT) and Modified Medical Research Council (MMRC) Dyspnea Scale were completed at the indicated timepoints: Baseline, Day 28 and Day 84. CAT and MMRC scales are prestned as: 1.I never cough/I cough all the time 2.I have no phelgm in my chest at all/My chest is completely full of phelgm 3. My chest does not feel tight at all/My chest feels very tight 4.Walk up hilll or stairs not breathless/Walk up hill or stairs very breathless 5. Not limited doing any home activities/Very limited doing any home activities 6. Confident leaving home/No confident leaving home 7. I sleep soundly/I don't sleep soundly because of my lung condition and 8. I have lots of energy/I have no energy at all. Baseline is defined as the assessment on Day 1. Score 0 indicates not troubled with breathlessness to 4:too breathless. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

ITT Population

Posted

Mean

Standard Deviation

Scores on a scale

Baseline, Day 28 and Day 84

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Secondary

Number of Participants With Treatment Failures

Treatment failure types are presented as: recurrent exacerbations, prolonged treatment of current exacerbation (beyond 14 days), additional treatment with systemic / oral corticosteroids and / or antibiotics, and requirement for invasive mechanical ventilation.

ITT Population

Posted

Number

Participants

13 weeks

ID	Title	Description
OG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
OG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.

Units	Counts
Participants	OG000

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Coronary artery stenosis	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected63 at risk EG0011 affected63 at risk
Constipation	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected63 at risk EG0010 affected63 at risk
Malaise	General disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected63 at risk EG0010 affected63 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 affected63 at risk EG0010 affected63 at risk
Pneumonia	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected63 at risk EG0011 affected63 at risk
Clostridium difficile infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected63 at risk EG0011 affected63 at risk
Blood sodium decreased	Investigations	MedDRA 18.1	Systematic Assessment	EG0000 affected63 at risk EG0011 affected63 at risk
Anxiety	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected63 at risk EG0010 affected63 at risk
Suicide attempt	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected63 at risk EG0010 affected63 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0009 affected63 at risk EG0014 affected63 at risk
Hyperventilation	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected63 at risk EG0011 affected63 at risk

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Dry mouth	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0005 affected63 at risk EG0012 affected63 at risk
Headache	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0005 affected63 at risk EG0017 affected63 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected63 at risk EG00122 affected63 at risk
Hypertension	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0004 affected63 at risk EG0010 affected63 at risk

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	Title	Description
BG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
BG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received placebo two inhalations per day administered via a dry powder inhaler for a duration of 84 days.			10	63	15	63
EG001	GSK2269557 1000 mcg	Participants received 1000 mcg of GSK2269557 two inhalations per day administered via a dry powder inhaler for a duration of 84 days.			8	63	31	63