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Clinical Trial Results:
A double-blind (sponsor unblind), placebo controlled, randomised, parallel group study to evaluate the safety, tolerability and pharmacokinetics of multiple doses of GSK2269557 administered as a dry powder to COPD patients and assessment of dose response using sputum biomarkers.

Summary
EudraCT number	2014-000313-31
Trial protocol	DE
Global end of trial date	18 Aug 2015

Results information
Results version number	v1(current)
This version publication date	21 Apr 2016
First version publication date	21 Apr 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

PII115119

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom,

Public contact

GSK Clinical Support Helpdesk, GlaxoSmithKline, +44 02089904466, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Clinical Support Helpdesk, GlaxoSmithKline, +44 02089904466, GSKClinicalSupportHD@gsk.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

04 Feb 2016

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

18 Aug 2015

Was the trial ended prematurely?

Main objective of the trial

Part A To assess the safety and tolerability of repeat doses of GSK2269557 administered as a dry powder to COPD patients. Part B To characterise the dose-response relationship of repeat doses of GSK2269557 administered as a dry powder to COPD patients using inflammatory cytokine biomarker.

Protection of trial subjects

A subject may withdraw from study treatment at any time at his/her own request, or may be withdrawn at any time at the discretion of the investigator for safety, behavioral or administrative reasons. There are subject specific dose adaptation/stopping criteria including Liver Chemistry and QTc Liver chemistry threshold stopping criteria have been designed to assure subject safety and to evaluate liver event aetiology (in alignment with the FDA premarketing clinical liver safety guidance). Subjects suffering from an exacerbation of COPD following screening or during the treatment phase of the study will be withdrawn.

Background therapy

Evidence for comparator

Actual start date of recruitment

31 Jul 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 64

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

This study was comprised of two parts. In Part A, participants were randomized to active or placebo treatment in a 3:1 ratio and in Part B, to placebo or one of the six doses of active treatment in an equal ratio. Each part comprised a separate sample of participants.

Period 1 title

Part A and Part B (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Part A: Placebo

Arm description

Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Lactose was contained in an inhalation device. Participants received multiple inhalation devices, each containing one of the 3 investigational medicinal products. Once daily for 14 consecutive days, participants took one inhalation from each device such that they received the total dose for the arm they were randomized to. Total dose for Part A: Placebo/GSK2269577 1000 mcg. Total dose for Part B: placebo/GSK2269577 100/200/500/700/1000/2000 mcg.

Part A: GSK2269557 1000 µg

Arm description

Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days.

Arm type

Experimental

Investigational medicinal product name

GSK2269557 500 micrograms

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

GSK2269557 500 mcg blended in lactose was contained in an inhalation device. Participants received multiple inhalation devices, each containing one of the 3 investigational medicinal products. Once daily for 14 consecutive days, participants took one inhalation from each device such that they received the total dose for the arm they were randomized to. Total dose for Part A: Placebo/GSK2269557 1000 mcg. Total dose for Part B: Placebo/GSK2269557 100/200/500/700/1000/2000 mcg.

Part B: Placebo

Arm description

Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Part B: GSK2269557 100 µg

Arm description

Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo.

Arm type

Experimental

Investigational medicinal product name

GSK2269557 100 micrograms

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

GSK2269557 100 micrograms (mcg) blended in lactose was contained in an inhalation device. Participants received multiple inhalation devices, each containing one of the 3 investigational medicinal products. Once daily for 14 consecutive days, participants took one inhalation from each device such that they received the total dose for the arm they were randomized to. Total dose for Part A: Placebo/GSK2269557 1000 mcg. Total dose for Part B: Placebo/GSK2269557 100/200/500/700/1000/2000 mcg.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Part B: GSK2269557 200 µg

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

GSK2269557 100 micrograms

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Part B: GSK2269557 500 µg

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

GSK2269557 500 micrograms

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Part B: GSK2269557 700 µg

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

GSK2269557 500 micrograms

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Investigational medicinal product name

GSK2269557 100 micrograms

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Part B: GSK2269557 1000 µg

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

GSK2269557 500 micrograms

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Part B: GSK2269557 2000 µg

Arm description

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.

Arm type

Experimental

Investigational medicinal product name

GSK2269557 500 micrograms

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

Number of subjects in period 1	Part A: Placebo	Part A: GSK2269557 1000 µg	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Started	7	21	5	5	5	5	6	5	5
Completed	7	21	5	5	5	5	6	5	5

Baseline characteristics

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Reporting group title

Part A: Placebo

Reporting group description

Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.

Reporting group title

Part A: GSK2269557 1000 µg

Reporting group description

Reporting group title

Part B: Placebo

Reporting group description

Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.

Reporting group title

Part B: GSK2269557 100 µg

Reporting group description

Reporting group title

Part B: GSK2269557 200 µg

Reporting group description

Reporting group title

Part B: GSK2269557 500 µg

Reporting group description

Reporting group title

Part B: GSK2269557 700 µg

Reporting group description

Reporting group title

Part B: GSK2269557 1000 µg

Reporting group description

Reporting group title

Part B: GSK2269557 2000 µg

Reporting group description

Reporting group values	Part A: Placebo	Part A: GSK2269557 1000 µg	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg	Total
Number of subjects	7	21	5	5	5	5	6	5	5	64
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	65.1 ± 5.81	60.5 ± 6.68	64.4 ± 4.45	61.6 ± 4.56	62.2 ± 8.23	65.4 ± 5.81	64.7 ± 7.26	62.4 ± 9.24	62.4 ± 6.43	-
Gender categorical
Units: Subjects
Female	1	7	2	4	1	0	3	3	3	24
Male	6	14	3	1	4	5	3	2	2	40
Race, Customized
Units: Subjects
White-White/Caucasian/European Heritage	7	21	5	5	5	5	6	5	5	64

End points

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Reporting group title

Part A: Placebo

Reporting group description

Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.

Reporting group title

Part A: GSK2269557 1000 µg

Reporting group description

Reporting group title

Part B: Placebo

Reporting group description

Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.

Reporting group title

Part B: GSK2269557 100 µg

Reporting group description

Reporting group title

Part B: GSK2269557 200 µg

Reporting group description

Reporting group title

Part B: GSK2269557 500 µg

Reporting group description

Reporting group title

Part B: GSK2269557 700 µg

Reporting group description

Reporting group title

Part B: GSK2269557 1000 µg

Reporting group description

Reporting group title

Part B: GSK2269557 2000 µg

Reporting group description

Primary: Part A: Number of participants with at least one non-serious adverse event (AE), serious adverse event (SAE), or drug-related adverse event

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End point title

Part A: Number of participants with at least one non-serious adverse event (AE), serious adverse event (SAE), or drug-related adverse event ^[1] ^[2]

End point description

An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase >=3 x upper limit of normal (ULN), and total bilirubin >=2 x ULN or international normalised ratio >1.5. AEs were classified as potentially drug-related, based on the investigator's judgement. Refer to the general AE/SAE module for a list of AEs and SAEs.

End point type

Primary

End point timeframe

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

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part A: Placebo	Part A: GSK2269557 1000 µg
Number of subjects analysed	7 ^[3]	21 ^[4]
Units: Participants
At least one AE	2	9
At least one SAE	0	1
At least one drug-related AE	2	6

Notes
[3] - Safety Population: all participants who received at least one dose of study treatment.
[4] - Safety Population: all participants who received at least one dose of study treatment.

No statistical analyses for this end point

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

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End point title

Part A: Change from Baseline in counts of white blood cells (WBC), total neutrophils (total absolute neutrophil count [ANC]), lymphocytes, monocytes, eosinophils, basophils, and platelets at the indicated time points ^[5] ^[6]

End point description

Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.

End point type

Primary

End point timeframe

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

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part A: Placebo	Part A: GSK2269557 1000 µg
Number of subjects analysed	7 ^[7]	21 ^[8]
Units: 10^9 cells per liter (GI/L)
arithmetic mean (standard deviation)
WBC; Day 7/Day 8, pre-dose	-0.736 ± 0.937	-0.08 ± 1.387
WBC; Day 14, 24 h post dose	-0.14 ± 1.22	-0.51 ± 0.947
Total ANC; Day 7/Day 8, pre-dose	-0.664 ± 0.624	-0.363 ± 1.342
Total ANC; Day 14, 24 h post dose	-0.153 ± 0.887	-0.547 ± 0.977
Lymphocytes; Day 7/Day 8, pre-dose	-0.033 ± 0.321	0.172 ± 0.597
Lymphocytes; Day 14, 24 h post dose	-0.049 ± 0.197	0.03 ± 0.245
Monocytes; Day 7/Day 8, pre-dose	-0.036 ± 0.074	0.046 ± 0.149
Monocytes; Day 14, 24 h post dose	0.039 ± 0.178	-0.022 ± 0.116
Eosinophils; Day 7/Day 8, pre-dose	-0.006 ± 0.051	0.032 ± 0.074
Eosinophils; Day 14, 24 h post dose	0.001 ± 0.085	0.01 ± 0.075
Basophils; Day 7/Day 8, pre-dose	-0.001 ± 0.006	0.006 ± 0.015
Basophils; Day 14, 24 h post dose	-0.003 ± 0.013	0.002 ± 0.018
Platelets; Day 7/Day 8, pre-dose	1.6 ± 20.58	17.9 ± 36.44
Platelets; Day 14, 24 h post dose	14.7 ± 21.8	23.5 ± 37.43

Notes
[7] - Safety Population
[8] - Safety Population

No statistical analyses for this end point

Primary: Part A: Change from Baseline in hemoglobin and mean corpuscle hemoglobin concentration (MCHC) at the indicated time points

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End point title

Part A: Change from Baseline in hemoglobin and mean corpuscle hemoglobin concentration (MCHC) at the indicated time points ^[9] ^[10]

End point description

Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. MCHC is one of the red blood cell (RBC) indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.

End point type

Primary

End point timeframe

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

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part A: Placebo	Part A: GSK2269557 1000 µg
Number of subjects analysed	7 ^[11]	21 ^[12]
Units: Grams/Liter (g/L)
arithmetic mean (standard deviation)
Hemoglobin; Day 7/Day 8, pre-dose	-1.3 ± 6.63	1.6 ± 4.17
Hemoglobin; Day 14, 24 h post dose	0.3 ± 6.97	1 ± 4.12
MCHC; Day 7/Day 8, pre-dose	-5.3 ± 7.32	-2.2 ± 4.54
MCHC; Day 14, 24 h post dose	-8.4 ± 4.39	-2.4 ± 6.45

Notes
[11] - Safety Population
[12] - Safety Population

No statistical analyses for this end point

Primary: Part A: Change from Baseline in hematocrit at the indicated time points

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End point title

Part A: Change from Baseline in hematocrit at the indicated time points ^[13] ^[14]

End point description

End point type

Primary

End point timeframe

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

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part A: Placebo	Part A: GSK2269557 1000 µg
Number of subjects analysed	7 ^[15]	21 ^[16]
Units: Fraction of 1
arithmetic mean (standard deviation)
Hematocrit; Day 7/Day 8, pre-dose	0.003 ± 0.023	0.007 ± 0.013
Hematocrit; Day 14, 24 h post dose	0.011 ± 0.019	0.006 ± 0.016

Notes
[15] - Safety Population
[16] - Safety Population

No statistical analyses for this end point

Primary: Part A: Change from Baseline in counts of RBCs and reticulocytes at the indicated time points

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End point title

Part A: Change from Baseline in counts of RBCs and reticulocytes at the indicated time points ^[17] ^[18]

End point description

End point type

Primary

End point timeframe

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

Notes
[17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part A: Placebo	Part A: GSK2269557 1000 µg
Number of subjects analysed	7 ^[19]	21 ^[20]
Units: 10^12 cells/Liter (TI/L)
arithmetic mean (standard deviation)
RBCs; Day 7/Day 8, pre-dose	0.023 ± 0.23	0.06 ± 0.141
RBCs; Day 14, 24 h post dose	0.119 ± 0.201	0.063 ± 0.16
Reticulocytes; Day 7/Day 8, pre-dose	0.005 ± 0.014	0.003 ± 0.009
Reticulocytes; Day 14, 24 h post dose	0.009 ± 0.014	0.003 ± 0.01

Notes
[19] - Safety Population
[20] - Safety Population

No statistical analyses for this end point

Primary: Part A: Change from Baseline in mean corpuscle hemoglobin (MCH) at the indicated time points

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End point title

Part A: Change from Baseline in mean corpuscle hemoglobin (MCH) at the indicated time points ^[21] ^[22]

End point description

Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. MCH is one of the red blood cell indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.

End point type

Primary

End point timeframe

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

Notes
[21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part A: Placebo	Part A: GSK2269557 1000 µg
Number of subjects analysed	7 ^[23]	21 ^[24]
Units: Picograms (pg)
arithmetic mean (standard deviation)
MCH; Day 7/Day 8, pre-dose	-0.46 ± 0.602	-0.06 ± 0.44
MCH; Day 14, 24 h post dose	-0.76 ± 0.586	-0.23 ± 0.593

Notes
[23] - Safety Population
[24] - Safety Population

No statistical analyses for this end point

Primary: Part A: Change from Baseline in mean corpuscle volume (MCV) at the indicated time points

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End point title

Part A: Change from Baseline in mean corpuscle volume (MCV) at the indicated time points ^[25] ^[26]

End point description

Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. MCV is one of the RBC indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.

End point type

Primary

End point timeframe

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

Notes
[25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part A: Placebo	Part A: GSK2269557 1000 µg
Number of subjects analysed	7 ^[27]	21 ^[28]
Units: Femtoliters (fL)
arithmetic mean (standard deviation)
MCV; Day 7/Day 8, pre-dose	0.11 ± 0.687	0.43 ± 0.697
MCV; Day 14, 24 h post dose	0.07 ± 0.848	-0.03 ± 1.193

Notes
[27] - Safety Population
[28] - Safety Population

No statistical analyses for this end point

Primary: Part A: Change from Baseline in albumin and total protein at the indicated time points

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End point title

Part A: Change from Baseline in albumin and total protein at the indicated time points ^[29] ^[30]

End point description

End point type

Primary

End point timeframe

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

Notes
[29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part A: Placebo	Part A: GSK2269557 1000 µg
Number of subjects analysed	7 ^[31]	21 ^[32]
Units: g/L
arithmetic mean (standard deviation)
Albumin; Day 7/Day 8, pre-dose	0.56 ± 2.23	0.8 ± 1.576
Albumin; Day 14, 24 h post dose	0.53 ± 2.379	0.52 ± 2.004
Total protein; Day 7/Day 8, pre-dose	0.56 ± 3.619	1.28 ± 2.599
Total protein; Day 14, 24 h post dose	0.84 ± 3.887	1.15 ± 2.606

Notes
[31] - Safety Population
[32] - Safety Population

No statistical analyses for this end point

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

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End point title

Part A: Change from Baseline in alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) at the indicated time points ^[33] ^[34]

End point description

End point type

Primary

End point timeframe

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

Notes
[33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available
[34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available.

End point values	Part A: Placebo	Part A: GSK2269557 1000 µg
Number of subjects analysed	7 ^[35]	21 ^[36]
Units: International Units (IU/L)
arithmetic mean (standard deviation)
ALT; Day 7/Day 8, pre-dose	2.46 ± 2.585	-0.61 ± 2.208
ALT; Day 14, 24 h post dose	1.51 ± 2.667	-0.4 ± 4.117
ALP; Day 7/Day 8, pre-dose	-0.64 ± 6.937	1.14 ± 8.586
ALP; Day 14, 24 h post dose	-2.23 ± 6.522	-0.21 ± 9.785
AST; Day 7/Day 8, pre-dose	3.14 ± 7.674	-1.03 ± 3.081
AST; Day 14, 24 h post dose	1.83 ± 4.75	-0.71 ± 2.592
GGT; Day 7/Day 8, pre-dose	-0.91 ± 2.203	0.11 ± 2.55
GGT; Day 14, 24 h post dose	-1.96 ± 2.873	-0.46 ± 4.187

Notes
[35] - Safety Population
[36] - Safety Population

No statistical analyses for this end point

Primary: Part A: Change from Baseline in creatinine, bilirubin, and total bilirubin at the indicated time points

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End point title

Part A: Change from Baseline in creatinine, bilirubin, and total bilirubin at the indicated time points ^[37] ^[38]

End point description

End point type

Primary

End point timeframe

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

Notes
[37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available
[38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part A: Placebo	Part A: GSK2269557 1000 µg
Number of subjects analysed	7 ^[39]	21 ^[40]
Units: Micromoles/Liter (micromol/L)
arithmetic mean (standard deviation)
Creatinine; Day 7/Day 8, pre-dose	2.31 ± 4.385	-0.62 ± 5.104
Creatinine; Day 14, 24 h post dose	3.64 ± 6.035	0.07 ± 3.259
Direct bilirubin; Day 7/Day 8, pre-dose	0.33 ± 0.419	0.04 ± 0.398
Direct bilirubin; Day 14, 24 h post dose	0.27 ± 0.496	0.1 ± 0.329
Total bilirubin; Day 7/Day 8, pre-dose	1.23 ± 2.447	0.02 ± 2.59
Total bilirubin; Day 14, 24 h post dose	0.9 ± 2.805	0.78 ± 1.72

Notes
[39] - Safety Population
[40] - Safety Population

No statistical analyses for this end point

Primary: Part A: Change from Baseline in calcium, potassium, sodium, glucose, and blood urea nitrogen (BUN) at the indicated time points

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End point title

Part A: Change from Baseline in calcium, potassium, sodium, glucose, and blood urea nitrogen (BUN) at the indicated time points ^[41] ^[42]

End point description

End point type

Primary

End point timeframe

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

Notes
[41] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available
[42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part A: Placebo	Part A: GSK2269557 1000 µg
Number of subjects analysed	7 ^[43]	21 ^[44]
Units: Millimoles per Liter (mmol/L)
arithmetic mean (standard deviation)
Calcium; Day 7/Day 8, pre-dose	0.033 ± 0.0535	0.033 ± 0.0617
Calcium; Day 14, 24 h post dose	0.033 ± 0.085	0.029 ± 0.0588
Glucose; Day 7/Day 8, pre-dose	-0.053 ± 0.3333	0.012 ± 0.2888
Glucose; Day 14, 24 h post dose	0.161 ± 0.2659	0.024 ± 0.4914
Potassium; Day 7/Day 8, pre-dose	0.103 ± 0.2279	0.011 ± 0.3539
Potassium; Day 14, 24 h post dose	0.161 ± 0.2562	0.065 ± 0.3347
Sodium; Day 7/Day 8, pre-dose	1.21 ± 2.8	0.88 ± 1.56
Sodium; Day 14, 24 h post dose	0.81 ± 1.297	0.83 ± 1.39
BUN; Day 7/Day 8, pre-dose	-0.53 ± 1.083	-0.192 ± 0.8124
BUN; Day 14, 24 h post dose	-0.464 ± 1.1979	0.111 ± 1.2147

Notes
[43] - Safety Population
[44] - Safety Population

No statistical analyses for this end point

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

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End point title

Part A: Number of participants meeting criteria of potential clinical importance for systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) at any visit post-Baseline ^[45] ^[46]

End point description

Baseline was the Day 1 pre-dose measurement. Vital signs (SBP, DBP, and HR) were measured at Day 1 (30 minutes [min] and 6 h post-dose), Day 7 (pre-dose), and Day 14 (24 h post-dose). Potential clinical concern range for SBP was <85 millimeters of mercury (mmHg) (low) and >160 mmHg (high), for DBP <45 mmHg (low) and >100 mmHg (high) and for HR <40 bpm and >110 bpm. All measurements were obtained in supine position, after a 5-minute rest. Day 7 assessments could be conducted on Day 7 or Day 8.

End point type

Primary

End point timeframe

Day 1, Day 7, and Day 14

Notes
[45] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available
[46] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part A: Placebo	Part A: GSK2269557 1000 µg
Number of subjects analysed	7 ^[47]	21 ^[48]
Units: Participants
SBP high	1	1
SBP low	0	0
DBP high	0	0
DBP low	1	0
HR high	0	1
HR low	0	0

Notes
[47] - Safety Population
[48] - Safety Population

No statistical analyses for this end point

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

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End point title

Part A: Number of participants with normal and abnormal (clinically significant or not clinically significant) findings in 12-lead electrocardiogram (ECG) at any visit post-Baseline ^[49] ^[50]

End point description

Baseline was the Day 1 (pre-dose) measurement. Single 12-lead ECGs were obtained using an ECG machine that automatically calculates the HR and measures PR, QRS, QT, and corrected QT intervals. Clinical significance was judged by the investigator. Day 7 assessments could be conducted on Day 7 or Day 8.

End point type

Primary

End point timeframe

Day 1, Day 7, and Day 14

Notes
[49] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available
[50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part A: Placebo	Part A: GSK2269557 1000 µg
Number of subjects analysed	7 ^[51]	21 ^[52]
Units: Participants
Normal	2	13
Abnormal - not clinically significant	5	8
Abnormal - clinically significant	0	0

Notes
[51] - Safety Population
[52] - Safety Population

No statistical analyses for this end point

Primary: Part A: Change from Baseline in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at the indicated time points

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End point title

Part A: Change from Baseline in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at the indicated time points ^[53] ^[54]

End point description

Baseline is Day 1 pre-dose. FEV1 and FVC are measures of lung function. FEV1 is defined as the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the maximum amount of air that can be forcibly blown out after a maximum inspiration. FEV1 and FVC measurements were repeated until three technically acceptable measurements (within 150 milliliters of each other) had been made. Only the best of three measurements were recorded. Baseline was the maximum of the planned pre-dose measurements on Day 1. Change from Baseline at any post-dose time point was calculated as the post-dose value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.

End point type

Primary

End point timeframe

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)

Notes
[53] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available
[54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part A: Placebo	Part A: GSK2269557 1000 µg
Number of subjects analysed	7 ^[55]	21 ^[56]
Units: Liters
arithmetic mean (confidence interval 95%)
FEV1, Day 1, 1 h post dose	0.15 (-0.01 to 0.3)	0.1 (0.02 to 0.18)
FEV1, Day 7/8, Pre-dose	0.03 (-0.09 to 0.15)	-0.04 (-0.13 to 0.05)
FEV1, Day 7/8, 1 h post dose	0.27 (0.15 to 0.39)	0.18 (0.1 to 0.26)
FEV1, Day 14, 24 h post dose	-0.01 (-0.09 to 0.06)	0.01 (-0.07 to 0.09)
FVC, Day 1, 1 h post dose	0.17 (-0.13 to 0.47)	0.16 (0.01 to 0.32)
FVC, Day 7/8, Predose	0.02 (-0.23 to 0.26)	0 (-0.12 to 0.13)
FVC, Day 7/8, 1 h post dose	0.33 (0.09 to 0.58)	0.22 (0.09 to 0.36)
FVC, Day 14, 24 h post dose	-0.04 (-0.3 to 0.22)	0.1 (-0.07 to 0.27)

Notes
[55] - Safety Population
[56] - Safety Population

No statistical analyses for this end point

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

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End point title

Part B: Adjusted median response of cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor alpha [TNFalpha]) concentrations in induced sputum, on Day 7 and Day 14 ^[57]

End point description

This outcome measure was used to estimate the inhibition levels of various doses of GSK2269557 by analyzing inflammatory cytokines IL6, IL8, and TNF alpha using Bayesian methods of statistical analysis, using non-informative prior distributions for all modeling parameters. Posterior medians (adjusted median response) and 95% credible intervals are reported here as medians and 95% confidence intervals respectively. 95% credible interval is reported as 2-sided 95% confidence in the statistical analyses. Day 7 assessments could be conducted on Day 7 or Day 8.

End point type

Primary

End point timeframe

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

Notes
[57] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Number of subjects analysed	5 ^[58]	5 ^[59]	5 ^[60]	5 ^[61]	6 ^[62]	5 ^[63]	5 ^[64]
Units: Picograms/milliliter (pg/mL)
median (confidence interval 95%)
IL6, Day 7/Day 8	41.3 (22.07 to 78.24)	37.4 (19.64 to 70.65)	28.23 (14.8 to 53.18)	30.82 (16.23 to 58)	52.23 (28.73 to 94.94)	31.25 (16.01 to 63.01)	33.4 (17.52 to 63.23)
IL6, Day 14	35.15 (17.72 to 70.01)	37.6 (18.71 to 74.49)	28.27 (14.1 to 56.22)	22.68 (11.32 to 45.13)	35.19 (18.32 to 66.93)	42.56 (20.57 to 90.25)	41.52 (20.62 to 82.81)
IL8, Day 7/Day 8	2633.21 (1401.19 to 4879.27)	2118.15 (1157.33 to 3866.74)	1860.78 (995.35 to 3499.61)	1523.63 (834.99 to 2745.9)	2650.13 (1535.07 to 4634.07)	2636.08 (1412.65 to 4978.59)	2279.48 (1205.35 to 4210.75)
IL8, Day 14	2942.28 (1375.08 to 6216.67)	2664.75 (1269.52 to 5544.49)	1879.92 (876.5 to 4056.53)	1619.12 (778.39 to 3309.81)	1356.35 (696.37 to 2645.82)	2394.65 (1125.17 to 5196.2)	2170.41 (1010.85 to 4582.03)
TNFalpha, Day 7/Day 8	3.35 (1.22 to 8.98)	1.55 (0.57 to 4.33)	1.16 (0.42 to 3.25)	1.54 (0.57 to 4.19)	7.32 (3.02 to 17.85)	3.68 (1.26 to 10.51)	2.62 (0.94 to 7.15)
TNFalpha, Day 14	2.91 (1.26 to 6.54)	3.02 (1.33 to 7)	1.25 (0.55 to 2.9)	1.26 (0.55 to 2.87)	3.99 (1.86 to 8.5)	3 (1.34 to 6.75)	1.53 (0.66 to 3.47)

Notes
[58] - Safety Population
[59] - Safety Population
[60] - Safety Population
[61] - Safety Population
[62] - Safety Population
[63] - Safety Population
[64] - Safety Population

Statistical analysis 1

Statistical analysis description

Comparison of IL6 concentrations at Day 7

Comparison groups

Part B: Placebo v Part B: GSK2269557 100 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.599 ^[65]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

2.07

Notes
[65] - Posterior Probability the True Treatment Ratio <1 for Day 7.

Statistical analysis 2

Statistical analysis description

Comparison of IL6 concentrations at Day 14

Comparison groups

Part B: Placebo v Part B: GSK2269557 100 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.442 ^[66]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

1.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.43

upper limit

2.59

Notes
[66] - Posterior Probability the True Treatment Ratio <1 for Day 14

Statistical analysis 3

Statistical analysis description

Comparison of IL6 concentrations at Day 7

Comparison groups

Part B: Placebo v Part B: GSK2269557 200 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.823 ^[67]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.68

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

1.57

Notes
[67] - Posterior Probability the True Treatment Ratio <1 for Day 7

Statistical analysis 4

Statistical analysis description

Comparison of IL6 concentrations at Day 14

Comparison groups

Part B: Placebo v Part B: GSK2269557 200 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.69 ^[68]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.33

upper limit

1.97

Notes
[68] - Posterior Probability the True Treatment Ratio <1 for Day 14

Statistical analysis 5

Statistical analysis description

Comparison of IL6 concentrations at Day 7

Comparison groups

Part B: Placebo v Part B: GSK2269557 500 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.764 ^[69]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.33

upper limit

1.71

Notes
[69] - Posterior Probability the True Treatment Ratio <1 for Day 7

Statistical analysis 6

Statistical analysis description

Comparison of IL6 concentrations at Day 14

Comparison groups

Part B: Placebo v Part B: GSK2269557 500 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.841 ^[70]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.27

upper limit

1.56

Notes
[70] - Posterior Probability the True Treatment Ratio <1 for Day 14

Statistical analysis 7

Statistical analysis description

Comparison of IL8 concentrations at Day 7

Comparison groups

Part B: Placebo v Part B: GSK2269557 100 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.702 ^[71]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.35

upper limit

1.81

Notes
[71] - Posterior Probability the True Treatment Ratio <1 for Day 7

Statistical analysis 8

Statistical analysis description

Comparison of IL8 concentrations at Day 14

Comparison groups

Part B: Placebo v Part B: GSK2269557 100 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.578 ^[72]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.33

upper limit

2.47

Notes
[72] - Posterior Probability the True Treatment Ratio <1 for Day 14

Statistical analysis 9

Statistical analysis description

Comparison of IL8 concentrations at Day 7

Comparison groups

Part B: Placebo v Part B: GSK2269557 200 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.783 ^[73]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.71

Confidence interval

level

95%

sides

2-sided

lower limit

0.29

upper limit

1.7

Notes
[73] - Posterior Probability the True Treatment Ratio <1 for Day 7

Statistical analysis 10

Statistical analysis description

Comparison of IL8 concentrations at Day 14

Comparison groups

Part B: Placebo v Part B: GSK2269557 200 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.797 ^[74]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.22

upper limit

1.87

Notes
[74] - Posterior Probability the True Treatment Ratio <1 for Day 14

Statistical analysis 11

Statistical analysis description

Comparison of IL8 concentrations at Day 7

Comparison groups

Part B: Placebo v Part B: GSK2269557 500 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.919 ^[75]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.58

Confidence interval

level

95%

sides

2-sided

lower limit

0.27

upper limit

1.26

Notes
[75] - Posterior Probability the True Treatment Ratio <1 for Day 7

Statistical analysis 12

Statistical analysis description

Comparison of IL8 concentrations at Day 14

Comparison groups

Part B: Placebo v Part B: GSK2269557 500 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.892 ^[76]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.55

Confidence interval

level

95%

sides

2-sided

lower limit

0.21

upper limit

1.43

Notes
[76] - Posterior Probability the True Treatment Ratio <1 for Day 14

Statistical analysis 13

Statistical analysis description

Comparison of TNFalpha concentrations at Day 7

Comparison groups

Part B: Placebo v Part B: GSK2269557 100 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.86 ^[77]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.47

Confidence interval

level

95%

sides

2-sided

lower limit

0.11

upper limit

1.93

Notes
[77] - Posterior Probability the True Treatment Ratio <1 for Day 7

Statistical analysis 14

Statistical analysis description

Comparison of TNFalpha concentrations at Day 14

Comparison groups

Part B: Placebo v Part B: GSK2269557 100 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.463 ^[78]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

1.05

Confidence interval

level

95%

sides

2-sided

lower limit

0.38

upper limit

2.86

Notes
[78] - Posterior Probability the True Treatment Ratio <1 for Day 14

Statistical analysis 15

Statistical analysis description

Comparison of TNFalpha concentrations at Day 7

Comparison groups

Part B: Placebo v Part B: GSK2269557 200 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.932 ^[79]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.35

Confidence interval

level

95%

sides

2-sided

lower limit

0.09

upper limit

1.42

Notes
[79] - Posterior Probability the True Treatment Ratio <1 for Day 7

Statistical analysis 16

Statistical analysis description

Comparison of TNFalpha concentrations at Day 14

Comparison groups

Part B: Placebo v Part B: GSK2269557 200 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.952 ^[80]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.43

Confidence interval

level

95%

sides

2-sided

lower limit

0.16

upper limit

1.17

Notes
[80] - Posterior Probability the True Treatment Ratio <1 for Day 14

Statistical analysis 17

Statistical analysis description

Comparison of TNFalpha concentrations at Day 7

Comparison groups

Part B: Placebo v Part B: GSK2269557 500 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.873 ^[81]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.46

Confidence interval

level

95%

sides

2-sided

lower limit

0.12

upper limit

1.81

Notes
[81] - Posterior Probability the True Treatment Ratio <1 for Day 7

Statistical analysis 18

Statistical analysis description

Comparison of TNFalpha concentrations at Day 14

Comparison groups

Part B: Placebo v Part B: GSK2269557 500 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.953 ^[82]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.43

Confidence interval

level

95%

sides

2-sided

lower limit

0.16

upper limit

1.16

Notes
[82] - Posterior Probability the True Treatment Ratio <1 for Day 14

Statistical analysis 19

Statistical analysis description

Comparison of IL6 concentrations at Day 7

Comparison groups

Part B: Placebo v Part B: GSK2269557 700 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.281 ^[83]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

1.26

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

2.82

Notes
[83] - Posterior Probability the True Treatment Ratio <1 for Day 7

Statistical analysis 20

Statistical analysis description

Comparison of IL6 concentrations at Day 14

Comparison groups

Part B: Placebo v Part B: GSK2269557 700 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5 ^[84]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.42

upper limit

2.35

Notes
[84] - Posterior Probability the True Treatment Ratio <1 for Day 14

Statistical analysis 21

Statistical analysis description

Comparison of IL6 concentrations at Day 7

Comparison groups

Part B: Placebo v Part B: GSK2269557 1000 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.744 ^[85]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.76

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

1.77

Notes
[85] - Posterior Probability the True Treatment Ratio <1 for Day 7

Statistical analysis 22

Statistical analysis description

Comparison of IL6 concentrations at Day 14

Comparison groups

Part B: Placebo v Part B: GSK2269557 1000 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.334 ^[86]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

1.21

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

3.04

Notes
[86] - Posterior Probability the True Treatment Ratio <1 for Day 14

Statistical analysis 23

Statistical analysis description

Comparison of IL6 concentrations at Day 7

Comparison groups

Part B: Placebo v Part B: GSK2269557 2000 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.698 ^[87]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.35

upper limit

1.85

Notes
[87] - Posterior Probability the True Treatment Ratio <1 for Day 7

Statistical analysis 24

Statistical analysis description

Comparison of IL6 concentrations at Day 14

Comparison groups

Part B: Placebo v Part B: GSK2269557 2000 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.353 ^[88]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

1.18

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

2.88

Notes
[88] - Posterior Probability the True Treatment Ratio <1 for Day 14

Statistical analysis 25

Statistical analysis description

Comparison of IL8 concentrations at Day 7

Comparison groups

Part B: Placebo v Part B: GSK2269557 700 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.489 ^[89]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.45

upper limit

2.26

Notes
[89] - Posterior Probability the True Treatment Ratio <1 for Day 7

Statistical analysis 26

Statistical analysis description

Comparison of IL8 concentrations at Day 14

Comparison groups

Part B: Placebo v Part B: GSK2269557 700 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.94 ^[90]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.46

Confidence interval

level

95%

sides

2-sided

lower limit

0.17

upper limit

1.23

Notes
[90] - Posterior Probability the True Treatment Ratio <1 for Day 14

Statistical analysis 27

Statistical analysis description

Comparison of IL8 concentrations at Day 7

Comparison groups

Part B: Placebo v Part B: GSK2269557 1000 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.495 ^[91]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.42

upper limit

2.4

Notes
[91] - Posterior Probability the True Treatment Ratio <1 for Day 7

Statistical analysis 28

Statistical analysis description

Comparison of IL8 concentrations at Day 14

Comparison groups

Part B: Placebo v Part B: GSK2269557 1000 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.647 ^[92]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.28

upper limit

2.37

Notes
[92] - Posterior Probability the True Treatment Ratio <1 for Day 14

Statistical analysis 29

Statistical analysis description

Comparison of IL8 concentrations at Day 7

Comparison groups

Part B: Placebo v Part B: GSK2269557 2000 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.646 ^[93]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

1.86

Notes
[93] - Posterior Probability the True Treatment Ratio <1 for Day 7

Statistical analysis 30

Statistical analysis description

Comparison of IL8 concentrations at Day 14

Comparison groups

Part B: Placebo v Part B: GSK2269557 2000 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.741 ^[94]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.29

upper limit

1.9

Notes
[94] - Posterior Probability the True Treatment Ratio <1 for Day 14

Statistical analysis 31

Statistical analysis description

Comparison of TNFalpha concentrations at Day 7

Comparison groups

Part B: Placebo v Part B: GSK2269557 700 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.109 ^[95]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

2.18

Confidence interval

level

95%

sides

2-sided

lower limit

0.62

upper limit

7.95

Notes
[95] - Posterior Probability the True Treatment Ratio <1 for Day 7

Statistical analysis 32

Statistical analysis description

Comparison of TNFalpha concentrations at Day 14

Comparison groups

Part B: Placebo v Part B: GSK2269557 700 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.24 ^[96]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

1.37

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

3.45

Notes
[96] - Posterior Probability the True Treatment Ratio <1 for Day 14

Statistical analysis 33

Statistical analysis description

Comparison of TNFalpha concentrations at Day 7

Comparison groups

Part B: Placebo v Part B: GSK2269557 1000 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.447 ^[97]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.27

upper limit

4.44

Notes
[97] - Posterior Probability the True Treatment Ratio <1 for Day 7

Statistical analysis 34

Statistical analysis description

Comparison of TNFalpha concentrations at Day 14

Comparison groups

Part B: Placebo v Part B: GSK2269557 1000 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.472 ^[98]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

2.74

Notes
[98] - Posterior Probability the True Treatment Ratio <1 for Day 14

Statistical analysis 35

Statistical analysis description

Comparison of TNFalpha concentrations at Day 7

Comparison groups

Part B: Placebo v Part B: GSK2269557 2000 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.698 ^[99]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.21

upper limit

2.9

Notes
[99] - Posterior Probability the True Treatment Ratio <1 for Day 7

Statistical analysis 36

Statistical analysis description

Comparison of TNFalpha concentrations at Day 14

Comparison groups

Part B: Placebo v Part B: GSK2269557 2000 µg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.911 ^[100]

Method

Posterior Probability

Parameter type

Adjusted Median Ratio

Point estimate

0.53

Confidence interval

level

95%

sides

2-sided

lower limit

0.21

upper limit

1.37

Notes
[100] - Posterior Probability the True Treatment Ratio <1 for Day 14

Secondary: Part A: Day 1 plasma concentration of GSK2269557 up to 6 hours post dose

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End point title

Part A: Day 1 plasma concentration of GSK2269557 up to 6 hours post dose ^[101]

End point description

A 2 mL blood sample for pharmacokinetic (PK) analysis was collected at each of the indicated time point. Only those participants who were available at the indicated time points were analyzed (represented by n=X in the category titles). A value of 99999 indicates that the geometric mean or 95% confidence interval is not available.

End point type

Secondary

End point timeframe

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

Notes
[101] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part A: GSK2269557 1000 µg
Number of subjects analysed	21 ^[102]
Units: pg/mL
geometric mean (confidence interval 95%)
Pre-dose; n=0	99999 (99999 to 99999)
5 min; n=21	386.2 (287.5 to 518.7)
30 min; n=21	337.2 (274.6 to 414)
1 h; n=21	379.1 (320.2 to 448.9)
2 h; n=21	531.1 (448.2 to 629.4)
4 h; n=21	419.5 (357.6 to 492.1)
6 h; n=21	334.4 (287 to 389.6)

Notes
[102] - PK Population: participants in the Safety Population for whom a PK sample was obtained and analyzed.

No statistical analyses for this end point

Secondary: Part B: Day 1 plasma concentration of GSK2269557 up to 6 hours post dose

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End point title

Part B: Day 1 plasma concentration of GSK2269557 up to 6 hours post dose ^[103]

End point description

A 2 mL blood sample for pharmacokinetic (PK) analysis was collected at each of the indicated time point. Concentration measurements were log-transformed. Only those participants who were available at the indicated time points were analyzed (represented by n=X,X in the category titles). A value of 99999 indicates that the geometric mean or 95% confidence interval is not available.

End point type

Secondary

End point timeframe

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

Notes
[103] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Number of subjects analysed	5 ^[104]	5 ^[105]	5 ^[106]	6 ^[107]	5 ^[108]	5 ^[109]
Units: pg/mL
geometric mean (confidence interval 95%)
Pre-dose; n=0,0,0,0,0,0,0	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)
5 min; n=5,5,5,6,5,5,5	55.3 (33.7 to 90.7)	80.4 (38.4 to 168.2)	173.1 (88.4 to 339)	466.6 (147.3 to 1478)	853.4 (380.2 to 1915.6)	982.9 (311.1 to 3105.3)
30 min; n=5,5,5,6,5,5,5	51.7 (36.2 to 74.1)	73.8 (41.6 to 130.8)	203 (111.2 to 370.5)	402.3 (218 to 742.5)	556.9 (384.8 to 806)	1011.6 (757.1 to 1351.6)
1 h; n=5,5,5,6,5,5,5	61.3 (45.7 to 82.3)	77.2 (44.1 to 135.2)	253.2 (155 to 413.8)	429.1 (294.2 to 626)	599.7 (370.5 to 970.7)	1203.3 (799.1 to 1812)
2 h; n=5,5,5,6,5,5,5	60.6 (44.8 to 81.9)	88.8 (60.2 to 130.9)	300.9 (173.7 to 521.1)	556.7 (372.4 to 832.3)	672.3 (434 to 1041.5)	1402 (892.8 to 2201.4)
4 h; n=5,5,5,6,5,5,5	45 (33.1 to 61.2)	73.4 (60.5 to 89.1)	251 (146 to 431.6)	391.6 (303.3 to 505.5)	468.7 (305.5 to 719.2)	1098.5 (781.9 to 1543.2)
6 h; n=5,5,5,6,5,5,5	38.3 (29.7 to 49.5)	63.8 (50.7 to 80.3)	201.5 (128.3 to 316.6)	294.6 (222.3 to 390.4)	466.5 (273.1 to 796.6)	900.8 (723.8 to 1121)

Notes
[104] - PK Population
[105] - PK Population
[106] - PK Population
[107] - PK Population
[108] - PK Population
[109] - PK Population

No statistical analyses for this end point

Secondary: Part A: Maximum observed plasma concentration (Cmax) of GSK2269557 on Day 7

Top of page

End point title

Part A: Maximum observed plasma concentration (Cmax) of GSK2269557 on Day 7 ^[110]

End point description

Blood samples were collected to determine the plasma concentrations of GSK2269557 immediately after dosing on Day 7. Day 7 sampling could be done on Day 7 or Day 8.

End point type

Secondary

End point timeframe

Day 7 immediately after dosing

Notes
[110] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part A: GSK2269557 1000 µg
Number of subjects analysed	21 ^[111]
Units: pg/mL
geometric mean (confidence interval 95%)	1109.1 (901.5 to 1364.5)

Notes
[111] - PK Population

No statistical analyses for this end point

Secondary: Part B: Maximum observed plasma concentration (Cmax) of GSK2269557 on Day 7

Top of page

End point title

Part B: Maximum observed plasma concentration (Cmax) of GSK2269557 on Day 7 ^[112]

End point description

Blood samples were collected to determine the plasma concentrations of GSK2269557 immediately after dosing on Day 7. Concentration values were log-transformed. Day 7 sampling could be done on Day 7 or Day 8.

End point type

Secondary

End point timeframe

Day 7 immediately after dosing

Notes
[112] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Number of subjects analysed	5 ^[113]	5 ^[114]	5 ^[115]	6 ^[116]	5 ^[117]	5 ^[118]
Units: pg/mL
geometric mean (confidence interval 95%)	109.6 (62.6 to 191.8)	203.4 (140.3 to 294.8)	511.8 (233.2 to 1123.3)	1022.2 (623.7 to 1675.2)	1655.1 (803.2 to 3410.4)	2923.4 (1769.4 to 4830)

Notes
[113] - PK Population
[114] - PK Population
[115] - PK Population
[116] - PK Population
[117] - PK Population
[118] - PK Population

No statistical analyses for this end point

Secondary: Part A: Trough concentration (Ctau) of GSK2269557 on Day 7 and Day 15

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End point title

Part A: Trough concentration (Ctau) of GSK2269557 on Day 7 and Day 15 ^[119]

End point description

Blood samples were collected to determine the (trough) plasma concentration of GSK2269557 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.

End point type

Secondary

End point timeframe

Day 7 and Day 15

Notes
[119] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part A: GSK2269557 1000 µg
Number of subjects analysed	21 ^[120]
Units: pg/mL
geometric mean (confidence interval 95%)
Day 7/Day 8	604.1 (496.6 to 735)
Day 15	711.2 (561.8 to 900.3)

Notes
[120] - PK Population

No statistical analyses for this end point

Secondary: Part B: Trough concentration (Ctau) of GSK2269557 on Day 7 and Day 15

Top of page

End point title

Part B: Trough concentration (Ctau) of GSK2269557 on Day 7 and Day 15 ^[121]

End point description

End point type

Secondary

End point timeframe

Day 7 and Day 15

Notes
[121] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Number of subjects analysed	5 ^[122]	5 ^[123]	5 ^[124]	6 ^[125]	5 ^[126]	5 ^[127]
Units: pg/mL
geometric mean (confidence interval 95%)
Day 7/Day 8	55.3 (41.22 to 74.21)	119.17 (78.47 to 180.97)	314.38 (182.64 to 541.16)	588.09 (486.63 to 710.69)	724.33 (581.37 to 902.45)	1468.94 (1000.5 to 2156.7)
Day 15	74.93 (48.26 to 116.33)	128.71 (92.02 to 180.03)	237.36 (66.38 to 848.74)	665.9 (497.61 to 891.1)	1218.5 (985.88 to 1506.01)	1767.34 (1079.72 to 2892.86)

Notes
[122] - PK Population
[123] - PK Population
[124] - PK Population
[125] - PK Population
[126] - PK Population
[127] - PK Population

No statistical analyses for this end point

Secondary: Part B: Number of times rescue medication was used by participants daily, during the treatment period

Top of page

End point title

Part B: Number of times rescue medication was used by participants daily, during the treatment period ^[128]

End point description

Rescue medication was identified from concomitant medication records and the patient diaries which were provided to the participants to record data throughout the treatment period. Only participants who used rescue medication were analyzed. The value 99999 indicates that the standard deviation could not be calculated as only one participant was analyzed.

End point type

Secondary

End point timeframe

Day 1 to Day 15

Notes
[128] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Number of subjects analysed	3 ^[129]	1 ^[130]	1 ^[131]	0 ^[132]	1 ^[133]	3 ^[134]	1 ^[135]
Units: Number of times
arithmetic mean (standard deviation)	2 ± 0	2.3 ± 99999	2.2 ± 99999	±	1 ± 99999	1.4 ± 0.63	1.9 ± 99999

Notes
[129] - Safety Population
[130] - Safety Population
[131] - Safety Population
[132] - Safety Population
[133] - Safety Population
[134] - Safety Population
[135] - Safety Population

No statistical analyses for this end point

Secondary: Part B: Number of participants with at least one non-serious adverse event (AE), serious adverse event (SAE), or drug-related adverse event

Top of page

End point title

Part B: Number of participants with at least one non-serious adverse event (AE), serious adverse event (SAE), or drug-related adverse event ^[136]

End point description

End point type

Secondary

End point timeframe

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

Notes
[136] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Number of subjects analysed	5 ^[137]	5 ^[138]	5 ^[139]	5 ^[140]	6 ^[141]	5 ^[142]	5 ^[143]
Units: Participants
At least one AE	3	3	2	1	3	4	2
At least one SAE	0	0	0	0	0	0	0
At least one drug-related AE	0	0	1	0	3	4	2

Notes
[137] - Safety Population
[138] - Safety Population
[139] - Safety Population
[140] - Safety Population
[141] - Safety Population
[142] - Safety Population
[143] - Safety Population

No statistical analyses for this end point

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

Top of page

End point title

Part B: Change from Baseline in counts of basophils, eosinophils, lymphocytes, monocytes, platelets, white blood cells (WBC), total neutrophils (total ANC) at the indicated time points ^[144]

End point description

Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.

End point type

Secondary

End point timeframe

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

Notes
[144] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Number of subjects analysed	5 ^[145]	5 ^[146]	5 ^[147]	5 ^[148]	6 ^[149]	4 ^[150]	5 ^[151]
Units: 10^9 cells per liter (GI/L)
arithmetic mean (standard deviation)
Basophils; Day 7/Day 8, pre-dose	0.014 ± 0.0241	-0.002 ± 0.0228	0.01 ± 0.0187	0.004 ± 0.0182	0.007 ± 0.0052	-0.005 ± 0.01	0 ± 0.01
Basophils; Day 14, 24 h post dose	0.004 ± 0.0167	-0.006 ± 0.0261	0.01 ± 0.0122	-0.002 ± 0.0192	0.007 ± 0.0175	-0.008 ± 0.0189	0.01 ± 0.0122
Eosinophils; Day 7/Day 8, pre-dose	-0.002 ± 0.0576	0.01 ± 0.0485	-0.034 ± 0.0702	-0.026 ± 0.0498	0.022 ± 0.1289	-0.002 ± 0.0287	0.012 ± 0.0438
Eosinophils; Day 14, 24 h post dose	0.046 ± 0.0472	-0.01 ± 0.0292	-0.046 ± 0.0378	-0.054 ± 0.1498	0.025 ± 0.1078	0.023 ± 0.0222	0.022 ± 0.0396
Lymphocytes; Day 7/Day 8, pre-dose	0.242 ± 0.4797	-0.178 ± 0.5657	-0.022 ± 0.1326	-0.094 ± 0.3092	0.093 ± 0.2813	-0.118 ± 0.3223	-0.218 ± 0.6236
Lymphocytes; Day 14, 24 h post dose	-0.09 ± 0.4499	-0.264 ± 0.3134	-0.216 ± 0.208	0.092 ± 0.9722	0.21 ± 0.3855	-0.243 ± 0.3054	-0.398 ± 0.736
Monocytes; Day 7/Day 8, pre-dose	-0.062 ± 0.0867	0.05 ± 0.0941	-0.02 ± 0.0806	0.05 ± 0.2108	0.018 ± 0.1209	0.165 ± 0.5166	-0.08 ± 0.1398
Monocytes; Day 14, 24 h post dose	-0.022 ± 0.0676	-0.012 ± 0.0926	-0.036 ± 0.0829	-0.004 ± 0.1313	0.03 ± 0.0699	0.108 ± 0.3437	-0.11 ± 0.0834
Platelets; Day 7/Day 8, pre-dose	-13.8 ± 14.22	-0.8 ± 18.07	10 ± 24.52	15.6 ± 17.78	11.7 ± 15.41	26.5 ± 32.77	-0.6 ± 14.4
Platelets; Day 14, 24 h post dose	-3.3 ± 22.25	-13 ± 26.52	-7.2 ± 20.41	-1.4 ± 44.86	7 ± 19.81	-8.3 ± 51.57	-11.4 ± 29.39
WBC; Day 7/Day 8, pre-dose	0.372 ± 1.5852	-0.024 ± 1.1519	0.102 ± 1.1107	0.926 ± 3.1314	0.497 ± 0.8673	0.5 ± 2.676	-0.802 ± 0.7889
WBC; Day 14, 24 h post dose	-0.49 ± 0.5204	-0.864 ± 1.4151	-0.164 ± 0.7907	-0.178 ± 2.2899	0.648 ± 1.143	0.825 ± 1.6016	-1.012 ± 1.3388
Total ANC; Day 7/Day 8, pre-dose	0.164 ± 0.9782	0.09 ± 0.6553	0.17 ± 1.0481	1.018 ± 2.6669	0.335 ± 0.5921	0.448 ± 2.153	-0.51 ± 0.285
Total ANC; Day 14, 24 h post dose	-0.44 ± 0.4288	-0.538 ± 1.1027	0.134 ± 0.801	-0.18 ± 1.469	0.385 ± 1.2151	0.958 ± 1.8925	-0.51 ± 0.7931

Notes
[145] - Safety Population
[146] - Safety Population
[147] - Safety Population
[148] - Safety Population
[149] - Safety Population
[150] - Safety Population
[151] - Safety Population

No statistical analyses for this end point

Secondary: Part B: Change from Baseline in hemoglobin and mean corpuscle hemoglobin concentration (MCHC) at the indicated time points

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End point title

Part B: Change from Baseline in hemoglobin and mean corpuscle hemoglobin concentration (MCHC) at the indicated time points ^[152]

End point description

Blood samples were collected for measurement for the indicated tests. MCHC is one of the red blood cell (RBC) indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.

End point type

Secondary

End point timeframe

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

Notes
[152] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Number of subjects analysed	5 ^[153]	5 ^[154]	5 ^[155]	5 ^[156]	6 ^[157]	4 ^[158]	5 ^[159]
Units: g/L
arithmetic mean (standard deviation)
Hemoglobin; Day 7/Day 8, pre-dose	3 ± 2.55	0.8 ± 5.76	3.8 ± 6.76	1 ± 4.74	0.3 ± 5.65	6 ± 5.89	1 ± 3.39
Hemoglobin; Day 14, 24 h post dose	4.2 ± 6.14	-1.2 ± 6.14	-0.6 ± 8.02	-2 ± 6.86	-2.2 ± 2.14	-0.3 ± 4.65	-0.2 ± 4.44
MCHC; Day 7/Day 8, pre-dose	-2.4 ± 2.07	-0.6 ± 8.17	-4 ± 7.31	-4.4 ± 9.61	0.5 ± 5.17	3.3 ± 8.18	7.8 ± 10.85
MCHC; Day 14, 24 h post dose	3.8 ± 5.07	-2.6 ± 3.51	-4.4 ± 8.73	3 ± 4	2.5 ± 3.83	-8.5 ± 7.59	1.6 ± 11.76

Notes
[153] - Safety Population
[154] - Safety Population
[155] - Safety Population
[156] - Safety Population
[157] - Safety Population
[158] - Safety Population
[159] - Safety Population

No statistical analyses for this end point

Secondary: Part B: Change from Baseline in counts of RBCs and reticulocytes at the indicated time points

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End point title

Part B: Change from Baseline in counts of RBCs and reticulocytes at the indicated time points ^[160]

End point description

End point type

Secondary

End point timeframe

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

Notes
[160] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Number of subjects analysed	5 ^[161]	5 ^[162]	5 ^[163]	5 ^[164]	6 ^[165]	4 ^[166]	5 ^[167]
Units: 10^12 cells/Liter (TI/L)
arithmetic mean (standard deviation)
RBC; Day 7/Day 8, pre-dose	0.076 ± 0.1148	0.036 ± 0.1549	0.18 ± 0.2703	0.058 ± 0.1314	-0.023 ± 0.1508	0.14 ± 0.0879	-0.058 ± 0.1252
RBC; Day 14, 24 h post dose	0.11 ± 0.1891	-0.038 ± 0.1663	0.034 ± 0.1785	-0.07 ± 0.1815	-0.083 ± 0.0958	0.042 ± 0.1031	-0.084 ± 0.1496
Reticulocytes; Day 7/Day 8, pre-dose	-0.00064 ± 0.01328	0.00714 ± 0.020838	0.01298 ± 0.011129	0.01258 ± 0.014565	0.00397 ± 0.008856	0.00882 ± 0.018576	0.01792 ± 0.012824
Reticulocytes; Day 14, 24 h post dose	0.0034 ± 0.014934	0.0006 ± 0.010183	0.01032 ± 0.015404	0.0156 ± 0.013092	-0.00172 ± 0.005382	-0.01063 ± 0.018329	0.00884 ± 0.015546

Notes
[161] - Safety Population
[162] - Safety Population
[163] - Safety Population
[164] - Safety Population
[165] - Safety Population
[166] - Safety Population
[167] - Safety Population

No statistical analyses for this end point

Secondary: Part B: Change from Baseline in hematocrit at the indicated time points

Top of page

End point title

Part B: Change from Baseline in hematocrit at the indicated time points ^[168]

End point description

Blood samples were collected for measurement for the indicated tests.Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.

End point type

Secondary

End point timeframe

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

Notes
[168] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Number of subjects analysed	5 ^[169]	5 ^[170]	5 ^[171]	5 ^[172]	6 ^[173]	4 ^[174]	5 ^[175]
Units: Fraction of 1
arithmetic mean (standard deviation)
Day 7/Day 8, pre-dose	0.012 ± 0.0084	0.004 ± 0.0182	0.018 ± 0.0259	0.01 ± 0.01	0 ± 0.0141	0.015 ± 0.0058	-0.01 ± 0.0235
Day 14, 24 h post dose	0.008 ± 0.0217	0 ± 0.0212	0.006 ± 0.0152	-0.012 ± 0.0217	-0.01 ± 0.0063	0.01 ± 0.0082	-0.004 ± 0.0207

Notes
[169] - Safety Population
[170] - Safety Population
[171] - Safety Population
[172] - Safety Population
[173] - Safety Population
[174] - Safety Population
[175] - Safety Population

No statistical analyses for this end point

Secondary: Part B: Change from Baseline in mean corpuscle hemoglobin (MCH) at the indicated time points

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End point title

Part B: Change from Baseline in mean corpuscle hemoglobin (MCH) at the indicated time points ^[176]

End point description

Blood samples were collected for measurement for the indicated tests. MCH is one of the red blood cell indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.

End point type

Secondary

End point timeframe

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

Notes
[176] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Number of subjects analysed	5 ^[177]	5 ^[178]	5 ^[179]	5 ^[180]	6 ^[181]	4 ^[182]	5 ^[183]
Units: pg
arithmetic mean (standard deviation)
Day 7/Day 8, pre-dose	0.18 ± 0.415	-0.06 ± 0.397	-0.36 ± 0.351	-0.08 ± 0.669	0.2 ± 0.529	0.35 ± 0.961	0.58 ± 0.46
Day 14, 24 h post dose	0.18 ± 0.626	0.02 ± 0.259	-0.34 ± 0.74	0.12 ± 0.396	0.1 ± 0.363	-0.33 ± 0.754	0.52 ± 0.268

Notes
[177] - Safety Population
[178] - Safety Population
[179] - Safety Population
[180] - Safety Population
[181] - Safety Population
[182] - Safety Population
[183] - Safety Population

No statistical analyses for this end point

Secondary: Part B: Change from Baseline in mean corpuscle volume (MCV) at the indicated time points

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End point title

Part B: Change from Baseline in mean corpuscle volume (MCV) at the indicated time points ^[184]

End point description

Blood samples were collected for measurement for the indicated tests. MCV is one of the RBC indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.

End point type

Secondary

End point timeframe

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

Notes
[184] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Number of subjects analysed	5 ^[185]	5 ^[186]	5 ^[187]	5 ^[188]	6 ^[189]	4 ^[190]	5 ^[191]
Units: fL
arithmetic mean (standard deviation)
MCV; Day 7/Day 8, pre-dose	1.24 ± 0.706	-0.14 ± 1.794	-0.12 ± 1.708	0.88 ± 1.085	0.42 ± 2.302	0.2 ± 0.583	-0.7 ± 2.719
MCV; Day 14, 24 h post dose	-0.66 ± 1.537	0.8 ± 1.257	0.26 ± 1.935	-0.62 ± 1.281	-0.53 ± 1.601	1.53 ± 0.699	0.98 ± 3.155

Notes
[185] - Safety Population
[186] - Safety Population
[187] - Safety Population
[188] - Safety Population
[189] - Safety Population
[190] - Safety Population
[191] - Safety Population

No statistical analyses for this end point

Secondary: Part B: Change from Baseline in albumin and total protein at the indicated time points

Top of page

End point title

Part B: Change from Baseline in albumin and total protein at the indicated time points ^[192]

End point description

End point type

Secondary

End point timeframe

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

Notes
[192] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Number of subjects analysed	5 ^[193]	5 ^[194]	5 ^[195]	5 ^[196]	6 ^[197]	5 ^[198]	5 ^[199]
Units: g/L
arithmetic mean (standard deviation)
Albumin; Day 7/Day 8, pre-dose	0.96 ± 1.773	1.22 ± 1.571	0.96 ± 3.012	0.88 ± 0.887	-0.6 ± 1.814	1.18 ± 1.069	0.3 ± 1.49
Albumin; Day 14, 24 h post dose	0.9 ± 2.965	0.7 ± 2.134	-0.12 ± 2.538	-1.16 ± 2.157	-1.13 ± 1.365	0.44 ± 1.001	0.26 ± 1.187
Total protein; Day 7/Day 8, pre-dose	1.34 ± 2.46	0.72 ± 1.203	2.22 ± 4.953	0.98 ± 2.039	-1.4 ± 2.662	1.78 ± 2.338	1.12 ± 1.571
Total protein; Day 14, 24 h post dose	0.96 ± 3.392	0.96 ± 2.393	-0.16 ± 3.737	-1.96 ± 3.635	-2.13 ± 2.156	0.72 ± 1.154	0.7 ± 2.277

Notes
[193] - Safety Population
[194] - Safety Population
[195] - Safety Population
[196] - Safety Population
[197] - Safety Population
[198] - Safety Population
[199] - Safety Population

No statistical analyses for this end point

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

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End point title

Part B: Change from Baseline in alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) at the indicated time points ^[200]

End point description

End point type

Secondary

End point timeframe

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

Notes
[200] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Number of subjects analysed	5 ^[201]	5 ^[202]	5 ^[203]	5 ^[204]	6 ^[205]	5 ^[206]	5 ^[207]
Units: International Units (IU/L)
arithmetic mean (standard deviation)
ALP; Day 7/Day 8, pre-dose	1.88 ± 5.45	1.62 ± 5.756	1.64 ± 7.946	5.7 ± 9.986	-0.95 ± 7.807	-0.92 ± 22.572	1.66 ± 5.465
ALP; Day 14, 24 h post dose	1.54 ± 4.503	4.78 ± 7.294	-0.2 ± 6.109	0.26 ± 9.829	-1.1 ± 8.535	-5.34 ± 19.016	5.2 ± 4.038
ALT; Day 7/Day 8, pre-dose	1.58 ± 2.24	3.66 ± 6.057	-2.44 ± 7.23	2.6 ± 4.994	-0.1 ± 2.994	-2.4 ± 5.036	1.42 ± 2.791
ALT; Day 14, 24 h post dose	0.36 ± 2.268	2.18 ± 3.17	-2.76 ± 6.176	0.84 ± 5.223	-0.72 ± 4.63	-2.86 ± 5.478	1.58 ± 3.754
AST; Day 7/Day 8, pre-dose	1.38 ± 2.464	3.76 ± 11.142	-0.42 ± 3.13	0.26 ± 5.185	-0.22 ± 3.672	-2.56 ± 5.607	3.04 ± 2.048
AST; Day 14, 24 h post dose	0.44 ± 1.691	0.16 ± 1.673	-2.44 ± 3.443	-1.64 ± 6.027	0.02 ± 3.129	-1.66 ± 4.536	2.66 ± 1.25
GGT; Day 7/Day 8, pre-dose	-0.6 ± 2.119	-0.3 ± 1.856	-0.96 ± 4.556	-0.3 ± 4.471	1.88 ± 4.747	-3.18 ± 9.7	0.74 ± 1.141
GGT; Day 14, 24 h post dose	-0.64 ± 0.934	0.1 ± 2.625	-2.64 ± 6.532	-0.72 ± 5.485	1.52 ± 5.783	-6.16 ± 17.113	0.54 ± 1.923

Notes
[201] - Safety Population
[202] - Safety Population
[203] - Safety Population
[204] - Safety Population
[205] - Safety Population
[206] - Safety Population
[207] - Safety Population

No statistical analyses for this end point

Secondary: Part B: Change from Baseline in creatinine, bilirubin, and total bilirubin at the indicated time points

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End point title

Part B: Change from Baseline in creatinine, bilirubin, and total bilirubin at the indicated time points ^[208]

End point description

End point type

Secondary

End point timeframe

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

Notes
[208] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Number of subjects analysed	5 ^[209]	5 ^[210]	5 ^[211]	5 ^[212]	6 ^[213]	5 ^[214]	5 ^[215]
Units: Micromoles/Liter (micromol/L)
arithmetic mean (standard deviation)
Direct bilirubin; Day 7/Day 8, pre-dose	-0.02 ± 0.327	0.24 ± 0.493	-0.28 ± 0.881	0.16 ± 0.261	0.23 ± 0.65	-0.18 ± 0.349	-0.32 ± 0.37
Direct bilirubin; Day 14, 24 h post dose	-0.1 ± 0.453	-0.02 ± 0.192	-0.58 ± 0.581	0.22 ± 0.409	0.2 ± 0.429	0.02 ± 0.554	-0.14 ± 0.456
Total bilirubin; Day 7/Day 8, pre-dose	0.28 ± 2.255	0.56 ± 2.151	-0.7 ± 4.049	0.72 ± 2.196	1.08 ± 2.775	-0.86 ± 1.75	-1.5 ± 1.739
Total bilirubin; Day 14, 24 h post dose	-0.5 ± 3.389	0.08 ± 0.87	-2.08 ± 2.387	0.52 ± 2.7	1.22 ± 3.008	0.5 ± 2.804	-1.06 ± 1.479
Creatinine; Day 7/Day 8, pre-dose	4.52 ± 4.533	1.6 ± 3.77	4.38 ± 2.217	-0.3 ± 4.567	0.52 ± 4.397	3.48 ± 3.084	0.76 ± 5.421
Creatinine; Day 14, 24 h post dose	1.58 ± 7.276	0.76 ± 3.319	4.84 ± 4.636	-0.46 ± 6.98	2.05 ± 3.17	1.36 ± 2.545	1.42 ± 5.058

Notes
[209] - Safety Population
[210] - Safety Population
[211] - Safety Population
[212] - Safety Population
[213] - Safety Population
[214] - Safety Population
[215] - Safety Population

No statistical analyses for this end point

Secondary: Part B: Change from Baseline in calcium, potassium, sodium, glucose, and blood urea nitrogen (BUN) at the indicated time points

Top of page

End point title

Part B: Change from Baseline in calcium, potassium, sodium, glucose, and blood urea nitrogen (BUN) at the indicated time points ^[216]

End point description

End point type

Secondary

End point timeframe

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

Notes
[216] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Number of subjects analysed	5 ^[217]	5 ^[218]	5 ^[219]	5 ^[220]	6 ^[221]	5 ^[222]	5 ^[223]
Units: Millimoles per Liter (mmol/L)
arithmetic mean (standard deviation)
Calcium; Day 7/Day 8, pre-dose	0.048 ± 0.0444	0.044 ± 0.0397	0.06 ± 0.0579	0.01 ± 0.0648	-0.008 ± 0.0655	0.066 ± 0.0811	0.044 ± 0.0365
Calcium; Day 14, 24 h post dose	0.024 ± 0.0865	-0.012 ± 0.0482	0.05 ± 0.0696	-0.01 ± 0.0758	-0.042 ± 0.0422	0.03 ± 0.0292	0.036 ± 0.0568
Glucose; Day 7/Day 8, pre-dose	-0.06 ± 0.2939	0.054 ± 0.4057	0.164 ± 0.1937	-0.43 ± 1.4084	-0.11 ± 0.5658	0.11 ± 0.4369	-0.246 ± 0.273
Glucose; Day 14, 24 h post dose	-0.086 ± 0.3743	-0.142 ± 0.3746	0.26 ± 0.5456	0.054 ± 0.2294	-0.34 ± 0.7332	-0.076 ± 0.3518	-0.314 ± 0.3871
Potassium; Day 7/Day 8, pre-dose	0.246 ± 0.3088	0.09 ± 0.2793	0.434 ± 0.5451	-0.204 ± 0.2563	0.135 ± 0.3172	0.276 ± 0.3566	0.192 ± 0.4587
Potassium; Day 14, 24 h post dose	0.19 ± 0.1944	0.12 ± 0.4282	0.336 ± 0.5268	-0.128 ± 0.3241	0.013 ± 0.203	0.14 ± 0.1259	0.072 ± 0.5946
Sodium; Day 7/Day 8, pre-dose	0 ± 1.206	0.6 ± 1.626	-0.12 ± 1.714	1.18 ± 1.139	-0.33 ± 2.072	0.7 ± 1.815	-0.84 ± 2.137
Sodium; Day 14, 24 h post dose	-0.16 ± 1.301	-0.04 ± 3.233	0.58 ± 1.399	0.46 ± 1.447	-0.18 ± 2.515	1.06 ± 1.074	-0.4 ± 2.72
Urea/BUN; Day 7/Day 8, pre-dose	0.314 ± 0.7077	-0.504 ± 0.6955	0.342 ± 0.8193	-0.91 ± 1.0653	-0.29 ± 0.4396	-0.244 ± 1.2909	0.162 ± 1.2285
Urea/BUN; Day 14, 24 h post dose	-0.232 ± 0.3592	-0.124 ± 0.7502	0.142 ± 1.0269	-0.906 ± 1.6431	-0.335 ± 0.2793	-0.364 ± 0.8554	0.186 ± 2.0478

Notes
[217] - Safety Population
[218] - Safety Population
[219] - Safety Population
[220] - Safety Population
[221] - Safety Population
[222] - Safety Population
[223] - Safety Population

No statistical analyses for this end point

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

Top of page

End point title

Part B: Number of participants meeting criteria of potential clinical importance for systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) at any visit post-Baseline ^[224]

End point description

End point type

Secondary

End point timeframe

Day 1, Day 7, and Day 14

Notes
[224] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Number of subjects analysed	5 ^[225]	5 ^[226]	5 ^[227]	5 ^[228]	6 ^[229]	5 ^[230]	5 ^[231]
Units: Participants
SBP high	0	0	1	1	1	0	0
SBP low	0	0	0	0	0	0	0
DBP high	0	0	0	0	0	0	0
DBP low	0	0	0	0	0	0	0
HR high	0	0	0	0	0	0	0
HR low	0	0	0	0	0	0	0

Notes
[225] - Safety Population
[226] - Safety Population
[227] - Safety Population
[228] - Safety Population
[229] - Safety Population
[230] - Safety Population
[231] - Safety Population

No statistical analyses for this end point

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

Top of page

End point title

Part B: Number of participants with normal and abnormal (clinically significant or not clinically significant) findings in 12-lead electrocardiogram (ECG) at any visit post-Baseline ^[232]

End point description

Baseline was the Day 1 (pre-dose) measurement. Single 12-lead ECGs were obtained using an ECG machine that automatically calculates the HR and measures PR, QRS, QT, and corrected QT intervals. Day 7 assessments could be conducted on Day 7 or Day 8.

End point type

Secondary

End point timeframe

Day 1, Day 7, and Day 14

Notes
[232] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Number of subjects analysed	5 ^[233]	5 ^[234]	5 ^[235]	5 ^[236]	6 ^[237]	5 ^[238]	5 ^[239]
Units: Participants
Normal	4	5	3	2	5	5	4
Abnormal - not clinically significant	1	0	2	3	1	0	1
Abnormal - clinically significant	0	0	0	0	0	0	0

Notes
[233] - Safety Population
[234] - Safety Population
[235] - Safety Population
[236] - Safety Population
[237] - Safety Population
[238] - Safety Population
[239] - Safety Population

No statistical analyses for this end point

Secondary: Part B: Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at Screening and Follow-up

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End point title

Part B: Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at Screening and Follow-up ^[240]

End point description

FEV1 and FVC are measures of lung function. FEV1 is defined as the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the maximum amount of air that can be forcibly blown out after a maximum inspiration. FEV1 and FVC measurements were repeated until three technically acceptable measurements (within 150 milliliters of each other) had been made. Only the best of three measurements were recorded.

End point type

Secondary

End point timeframe

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

Notes
[240] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was performed for this primary endpoint; thus, no data are available

End point values	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Number of subjects analysed	5 ^[241]	5 ^[242]	5 ^[243]	5 ^[244]	6 ^[245]	5 ^[246]	5 ^[247]
Units: Liters
arithmetic mean (confidence interval 95%)
FEV1, Screening	1.586 (1.093 to 2.079)	1.387 (0.783 to 1.99)	1.533 (0.784 to 2.282)	1.558 (0.916 to 2.199)	1.573 (1.092 to 2.055)	1.36 (1.126 to 1.594)	1.407 (0.768 to 2.046)
FEV1, Follow-up	1.494 (1.174 to 1.813)	1.272 (0.69 to 1.855)	1.523 (0.775 to 2.271)	1.34 (1.092 to 1.589)	1.501 (0.989 to 2.013)	1.405 (0.948 to 1.861)	1.431 (0.834 to 2.028)
FVC, Screening	3.05 (2.476 to 3.624)	3.08 (1.901 to 4.259)	3.632 (2.585 to 4.679)	4.348 (3.565 to 5.131)	3.277 (2.389 to 4.164)	2.958 (1.6 to 4.316)	3.156 (2.099 to 4.213)
FVC, Follow-up	2.96 (2.432 to 3.488)	3.042 (1.809 to 4.275)	3.764 (2.533 to 4.995)	4.192 (3.527 to 4.857)	3.137 (2.057 to 4.217)	3.03 (1.691 to 4.369)	3.192 (1.968 to 4.416)

Notes
[241] - Safety Population
[242] - Safety Population
[243] - Safety Population
[244] - Safety Population
[245] - Safety Population
[246] - Safety Population
[247] - Safety Population

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs), defined as those events occuring from the start of treatment until follow-up (up to approximately 19 days), are reported.

Adverse event reporting additional description

SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants who received at least one dose of study treatment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.1

Reporting group title

Part A: Placebo

Reporting group description

Participants received 2 inhalations of matching placebo once daily for 14 consecutive days.

Reporting group title

Part A: GSK2269557 1000 µg

Reporting group description

Reporting group title

Part B: Placebo

Reporting group description

Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days.

Reporting group title

Part B: GSK2269557 100 µg

Reporting group description

Reporting group title

Part B: GSK2269557 200 µg

Reporting group description

Reporting group title

Part B: GSK2269557 500 µg

Reporting group description

Reporting group title

Part B: GSK2269557 700 µg

Reporting group description

Reporting group title

Part B: GSK2269557 1000 µg

Reporting group description

Reporting group title

Part B: GSK2269557 2000 µg

Reporting group description

Serious adverse events	Part A: Placebo	Part A: GSK2269557 1000 µg	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 7 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	0 / 7 (0.00%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Part A: Placebo	Part A: GSK2269557 1000 µg	Part B: Placebo	Part B: GSK2269557 100 µg	Part B: GSK2269557 200 µg	Part B: GSK2269557 500 µg	Part B: GSK2269557 700 µg	Part B: GSK2269557 1000 µg	Part B: GSK2269557 2000 µg
Total subjects affected by non serious adverse events
subjects affected / exposed	2 / 7 (28.57%)	7 / 21 (33.33%)	3 / 5 (60.00%)	3 / 5 (60.00%)	2 / 5 (40.00%)	1 / 5 (20.00%)	3 / 6 (50.00%)	4 / 5 (80.00%)	2 / 5 (40.00%)
Nervous system disorders
Headache
subjects affected / exposed	1 / 7 (14.29%)	3 / 21 (14.29%)	1 / 5 (20.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	1 / 5 (20.00%)
occurrences all number	2	4	1	1	0	0	2	1	1
Dizziness
subjects affected / exposed	0 / 7 (0.00%)	0 / 21 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	0	0	1	0	0	1
General disorders and administration site conditions
Catheter site haematoma
subjects affected / exposed	0 / 7 (0.00%)	0 / 21 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	0	0	0	0	0	1
Vessel puncture site inflammation
subjects affected / exposed	0 / 7 (0.00%)	0 / 21 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	0	0	0	0	0	1
Eye disorders
Lacrimation increased
subjects affected / exposed	0 / 7 (0.00%)	0 / 21 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	0	0	0	0	0	1
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	1 / 7 (14.29%)	0 / 21 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0
Dry mouth
subjects affected / exposed	0 / 7 (0.00%)	0 / 21 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Toothache
subjects affected / exposed	0 / 7 (0.00%)	0 / 21 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 7 (14.29%)	4 / 21 (19.05%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	3 / 6 (50.00%)	4 / 5 (80.00%)	2 / 5 (40.00%)
occurrences all number	1	17	0	0	1	0	5	5	3
Oropharyngeal pain
subjects affected / exposed	0 / 7 (0.00%)	0 / 21 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Eczema
subjects affected / exposed	0 / 7 (0.00%)	0 / 21 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Hyperhidrosis
subjects affected / exposed	0 / 7 (0.00%)	0 / 21 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Psychiatric disorders
Sleep disorder
subjects affected / exposed	0 / 7 (0.00%)	0 / 21 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 7 (0.00%)	2 / 21 (9.52%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	2	0	1	0	0	0	0	0
Neck pain
subjects affected / exposed	0 / 7 (0.00%)	0 / 21 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Pain in extremity
subjects affected / exposed	0 / 7 (0.00%)	0 / 21 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	1	0	0	0	0	1
Spinal pain
subjects affected / exposed	0 / 7 (0.00%)	0 / 21 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	0	0	0	0	0	1
Infections and infestations
Gastroenteritis
subjects affected / exposed	1 / 7 (14.29%)	0 / 21 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	1 / 7 (14.29%)	1 / 21 (4.76%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	1	0	0	1	0	0	0	0
Oral herpes
subjects affected / exposed	1 / 7 (14.29%)	0 / 21 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Rhinitis
subjects affected / exposed	0 / 7 (0.00%)	0 / 21 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	1 / 5 (20.00%)
occurrences all number	0	0	0	1	0	0	0	1	1
Sinusitis
subjects affected / exposed	0 / 7 (0.00%)	0 / 21 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 5 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

03 Jul 2014

Amendment created to incorporate the comments received from the Ethics Committee and the Regulatory Authorities in Germany (BfArM).

09 Sep 2014

Amendment 2 was created to incorporate an early assessment of the exploratory data in sputum to help internal decision making

16 Feb 2015

Amendment 3 was created to incorporate Part B of the study (assessment of dose response using sputum biomarkers).

04 Mar 2015

Amendment 4 was created to include additional photosensitivity protection wording for consistency with other protocols for GSK2269557

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part A: Number of participants with at least one non-serious adverse event (AE), serious adverse event (SAE), or drug-related adverse event

Primary: Part A: Number of participants with at least one non-serious adverse event (AE), serious adverse event (SAE), or drug-related adverse event

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

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

Primary: Part A: Change from Baseline in hemoglobin and mean corpuscle hemoglobin concentration (MCHC) at the indicated time points

Primary: Part A: Change from Baseline in hemoglobin and mean corpuscle hemoglobin concentration (MCHC) at the indicated time points

Primary: Part A: Change from Baseline in hematocrit at the indicated time points

Primary: Part A: Change from Baseline in hematocrit at the indicated time points

Primary: Part A: Change from Baseline in counts of RBCs and reticulocytes at the indicated time points

Primary: Part A: Change from Baseline in counts of RBCs and reticulocytes at the indicated time points

Primary: Part A: Change from Baseline in mean corpuscle hemoglobin (MCH) at the indicated time points

Primary: Part A: Change from Baseline in mean corpuscle hemoglobin (MCH) at the indicated time points

Primary: Part A: Change from Baseline in mean corpuscle volume (MCV) at the indicated time points

Primary: Part A: Change from Baseline in mean corpuscle volume (MCV) at the indicated time points

Primary: Part A: Change from Baseline in albumin and total protein at the indicated time points

Primary: Part A: Change from Baseline in albumin and total protein at the indicated time points

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

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

Primary: Part A: Change from Baseline in creatinine, bilirubin, and total bilirubin at the indicated time points

Primary: Part A: Change from Baseline in creatinine, bilirubin, and total bilirubin at the indicated time points

Primary: Part A: Change from Baseline in calcium, potassium, sodium, glucose, and blood urea nitrogen (BUN) at the indicated time points

Primary: Part A: Change from Baseline in calcium, potassium, sodium, glucose, and blood urea nitrogen (BUN) at the indicated time points

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

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

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

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

Primary: Part A: Change from Baseline in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at the indicated time points

Primary: Part A: Change from Baseline in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at the indicated time points

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

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

Secondary: Part A: Day 1 plasma concentration of GSK2269557 up to 6 hours post dose

Secondary: Part A: Day 1 plasma concentration of GSK2269557 up to 6 hours post dose

Secondary: Part B: Day 1 plasma concentration of GSK2269557 up to 6 hours post dose

Secondary: Part B: Day 1 plasma concentration of GSK2269557 up to 6 hours post dose

Secondary: Part A: Maximum observed plasma concentration (Cmax) of GSK2269557 on Day 7

Secondary: Part A: Maximum observed plasma concentration (Cmax) of GSK2269557 on Day 7

Secondary: Part B: Maximum observed plasma concentration (Cmax) of GSK2269557 on Day 7

Secondary: Part B: Maximum observed plasma concentration (Cmax) of GSK2269557 on Day 7

Secondary: Part A: Trough concentration (Ctau) of GSK2269557 on Day 7 and Day 15

Secondary: Part A: Trough concentration (Ctau) of GSK2269557 on Day 7 and Day 15

Secondary: Part B: Trough concentration (Ctau) of GSK2269557 on Day 7 and Day 15

Secondary: Part B: Trough concentration (Ctau) of GSK2269557 on Day 7 and Day 15

Secondary: Part B: Number of times rescue medication was used by participants daily, during the treatment period

Secondary: Part B: Number of times rescue medication was used by participants daily, during the treatment period

Secondary: Part B: Number of participants with at least one non-serious adverse event (AE), serious adverse event (SAE), or drug-related adverse event

Secondary: Part B: Number of participants with at least one non-serious adverse event (AE), serious adverse event (SAE), or drug-related adverse event

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

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

Secondary: Part B: Change from Baseline in hemoglobin and mean corpuscle hemoglobin concentration (MCHC) at the indicated time points

Secondary: Part B: Change from Baseline in hemoglobin and mean corpuscle hemoglobin concentration (MCHC) at the indicated time points

Secondary: Part B: Change from Baseline in counts of RBCs and reticulocytes at the indicated time points

Secondary: Part B: Change from Baseline in counts of RBCs and reticulocytes at the indicated time points

Secondary: Part B: Change from Baseline in hematocrit at the indicated time points

Secondary: Part B: Change from Baseline in hematocrit at the indicated time points

Secondary: Part B: Change from Baseline in mean corpuscle hemoglobin (MCH) at the indicated time points

Secondary: Part B: Change from Baseline in mean corpuscle hemoglobin (MCH) at the indicated time points

Secondary: Part B: Change from Baseline in mean corpuscle volume (MCV) at the indicated time points

Secondary: Part B: Change from Baseline in mean corpuscle volume (MCV) at the indicated time points

Secondary: Part B: Change from Baseline in albumin and total protein at the indicated time points

Secondary: Part B: Change from Baseline in albumin and total protein at the indicated time points

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

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

Secondary: Part B: Change from Baseline in creatinine, bilirubin, and total bilirubin at the indicated time points

Secondary: Part B: Change from Baseline in creatinine, bilirubin, and total bilirubin at the indicated time points

Secondary: Part B: Change from Baseline in calcium, potassium, sodium, glucose, and blood urea nitrogen (BUN) at the indicated time points

Secondary: Part B: Change from Baseline in calcium, potassium, sodium, glucose, and blood urea nitrogen (BUN) at the indicated time points

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

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

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

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

Secondary: Part B: Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at Screening and Follow-up