Trial Outcomes & Findings for Single Doses of GSK3008348 in Idiopathic Pulmonary Fibrosis (IPF) Participants Using Positron Emission Tomography (PET) Imaging (NCT NCT03069989)

NCT ID: NCT03069989

Last Updated: 2019-08-12

Results Overview

The change in the uptake of \[18F\]-FBA-A20FMDV2 in the whole lung, assessed by VT derived from kinetic analysis of the dynamic PET data, was used to evaluate target engagement in the lung after single nebulized doses of GSK3008348. The per-Protocol population consisted of all participants in the Intent-to-Treat population who comply with the protocol and that had at least one evaluable PET measurement post-dose.

• Recruitment status: TERMINATED
• Study phase: PHASE1
• Target enrollment: 8 participants
• Primary outcome timeframe: Baseline (pre-dose) and 30 minutes post-dose
• Results posted on: 2019-08-12

Participant Flow

The study was conducted at 3 sites in the United Kingdom from 13-June-2017 to 18-July-2018. At the interim analysis following review of Cohort 1 data it was agreed to stop the study without proceeding into optional Cohort 2.

A total of 11 participants were screened, of which 3 were screening failures. Two screening failure participants did not meet inclusion/exclusion criteria and 1 participant withdrew consent. Hence, 8 participants were enrolled in this study.

Participant milestones

Measure	Placebo Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Dosing Period 1 (Up to 2 Days) STARTED	3	5
Dosing Period 1 (Up to 2 Days) COMPLETED	3	5
Dosing Period 1 (Up to 2 Days) NOT COMPLETED	0	0
Wash Out Period (Up to 28 Days)) STARTED	3	5
Wash Out Period (Up to 28 Days)) COMPLETED	3	5
Wash Out Period (Up to 28 Days)) NOT COMPLETED	0	0
Dosing Period 2 (Up to 16 Days) STARTED	3	5
Dosing Period 2 (Up to 16 Days) COMPLETED	2	5
Dosing Period 2 (Up to 16 Days) NOT COMPLETED	1	0

Reasons for withdrawal

Measure	Placebo Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Dosing Period 2 (Up to 16 Days) Protocol-defined stop criteria reached	1	0

Baseline Characteristics

Single Doses of GSK3008348 in Idiopathic Pulmonary Fibrosis (IPF) Participants Using Positron Emission Tomography (PET) Imaging

Baseline characteristics by cohort

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	Total n=8 Participants Total of all reporting groups
Age, Continuous	70.3 Years STANDARD_DEVIATION 3.06 • n=5 Participants	73.6 Years STANDARD_DEVIATION 2.30 • n=7 Participants	72.4 Years STANDARD_DEVIATION 2.92 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized White	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (pre-dose) and 30 minutes post-dose

Population: Per-Protocol Population. Only those participants with data available at the indicated time points were analyzed.

The change in the uptake of [18F]-FBA-A20FMDV2 in the whole lung, assessed by VT derived from kinetic analysis of the dynamic PET data, was used to evaluate target engagement in the lung after single nebulized doses of GSK3008348. The per-Protocol population consisted of all participants in the Intent-to-Treat population who comply with the protocol and that had at least one evaluable PET measurement post-dose.

Outcome measures

Measure	Placebo n=2 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: Volume of Distribution (VT) of [18F]-FBA-A20FMDV2 in the Whole Lung (Not Corrected for Air Volume) at 30 Minutes Post-dose Compared to Pre-dose Baseline	1.664 Milliliter per cubic centimeter(mL/cm^3) Geometric Coefficient of Variation 19.67	1.503 Milliliter per cubic centimeter(mL/cm^3) Geometric Coefficient of Variation 37.32
Period 2: Volume of Distribution (VT) of [18F]-FBA-A20FMDV2 in the Whole Lung (Not Corrected for Air Volume) at 30 Minutes Post-dose Compared to Pre-dose 30 minutes post-dose PET scan 1	1.572 Milliliter per cubic centimeter(mL/cm^3) Geometric Coefficient of Variation 8.56	1.198 Milliliter per cubic centimeter(mL/cm^3) Geometric Coefficient of Variation 44.37

PRIMARY outcome

Timeframe: Up to 62 days

Population: Intent-to-Treat Population.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. 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, is a congenital anomaly/birth defect, other situations judged by physician. Intent-to-Treat population consisted of all randomized participants who received at least one dose of study treatment.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	1 Participants	3 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population.

Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count, platelet count and WBC count. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count Basophils	0.000 Giga cells per liter Standard Deviation 0.0000	-0.008 Giga cells per liter Standard Deviation 0.0179
Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count Eosinophils	0.000 Giga cells per liter Standard Deviation 0.0000	0.018 Giga cells per liter Standard Deviation 0.0402
Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count Lymphocytes	0.267 Giga cells per liter Standard Deviation 0.0577	-0.086 Giga cells per liter Standard Deviation 0.3361
Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count Monocytes	-0.033 Giga cells per liter Standard Deviation 0.0577	-0.106 Giga cells per liter Standard Deviation 0.1232
Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count Total neutrophils	0.300 Giga cells per liter Standard Deviation 0.5292	-0.762 Giga cells per liter Standard Deviation 0.8135
Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count Platelet count	-3.0 Giga cells per liter Standard Deviation 16.46	-24.2 Giga cells per liter Standard Deviation 11.69
Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count WBC count	0.467 Giga cells per liter Standard Deviation 0.4933	-0.982 Giga cells per liter Standard Deviation 0.9509

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population.

Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count, platelet count and WBC count. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=2 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count Basophils	0.010 Giga cells per liter Standard Deviation 0.0424	-0.034 Giga cells per liter Standard Deviation 0.0365
Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count Eosinophils	0.025 Giga cells per liter Standard Deviation 0.0071	-0.030 Giga cells per liter Standard Deviation 0.1051
Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count Lymphocytes	0.485 Giga cells per liter Standard Deviation 0.1061	0.168 Giga cells per liter Standard Deviation 0.3269
Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count Monocytes	-0.050 Giga cells per liter Standard Deviation 0.1414	-0.046 Giga cells per liter Standard Deviation 0.1172
Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count Total neutrophils	-0.155 Giga cells per liter Standard Deviation 0.5728	-0.866 Giga cells per liter Standard Deviation 0.6179
Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count Platelet count	-2.5 Giga cells per liter Standard Deviation 16.26	15.8 Giga cells per liter Standard Deviation 12.87
Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count WBC count	0.270 Giga cells per liter Standard Deviation 0.5657	-0.748 Giga cells per liter Standard Deviation 0.7351

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population.

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Change From Baseline in Hematology Parameter: Hemoglobin	-4.3 Grams per liter Standard Deviation 2.89	-4.4 Grams per liter Standard Deviation 6.84

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=2 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: Change From Baseline in Hematology Parameter: Hemoglobin	-4.0 Grams per liter Standard Deviation 5.66	-8.8 Grams per liter Standard Deviation 3.56

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population.

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Change From Baseline in Hematology Parameter: Hematocrit	0.000 Proportion of red blood cells in blood Standard Deviation 0.0000	-0.016 Proportion of red blood cells in blood Standard Deviation 0.0270

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=2 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: Change From Baseline in Hematology Parameter: Hematocrit	-0.013 Proportion of red blood cells in blood Standard Deviation 0.0057	-0.028 Proportion of red blood cells in blood Standard Deviation 0.0141

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population.

Blood samples were collected to analyze the hematology parameter: mean corpuscle hemoglobin. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin	-0.30 Picrograms Standard Deviation 0.265	0.10 Picrograms Standard Deviation 0.500

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.

Blood samples were collected to analyze the hematology parameter: mean corpuscle hemoglobin. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=2 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin	-0.75 Picrograms Standard Deviation 0.212	-0.50 Picrograms Standard Deviation 0.361

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population.

Blood samples were collected to analyze the hematology parameter: mean corpuscle volume. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume	1.00 Femtoliters Standard Deviation 1.000	-0.58 Femtoliters Standard Deviation 1.559

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.

Blood samples were collected to analyze the hematology parameter: mean corpuscle volume. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=2 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume	-2.35 Femtoliters Standard Deviation 1.061	-1.62 Femtoliters Standard Deviation 1.213

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population.

Blood samples were collected to analyze the hematology parameter: red blood cell count. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Change From Baseline in Hematology Parameter: Red Blood Cell Count	-0.093 Trillion cells per liter Standard Deviation 0.0702	-0.168 Trillion cells per liter Standard Deviation 0.2946

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.

Blood samples were collected to analyze the hematology parameter: red blood cell count. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=2 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: Change From Baseline in Hematology Parameter: Red Blood Cell Count	-0.010 Trillion cells per liter Standard Deviation 0.1556	-0.226 Trillion cells per liter Standard Deviation 0.1372

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population. Only those participants available at the indicated time points were analyzed (represented by n= X in the category titles).

Blood samples were collected to analyze the chemistry parameters: alkaline phosphatase, alanine amino transferase, aspartate amino transferase, creatine kinase and gamma glutamyl transferase. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase Alkaline phosphatase, n=3,5	-1.7 International units per liter Standard Deviation 1.53	-3.4 International units per liter Standard Deviation 10.43
Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase Alanine amino transferase, n=3,5	1.3 International units per liter Standard Deviation 1.53	-0.6 International units per liter Standard Deviation 1.14
Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase Aspartate amino transferase, n=2,3	0.0 International units per liter Standard Deviation 2.83	-0.3 International units per liter Standard Deviation 3.06
Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase Creatine kinase, n=3,5	-95.0 International units per liter Standard Deviation 76.62	-13.8 International units per liter Standard Deviation 9.31
Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase Gamma glutamyl transferase, n=3,5	-1.0 International units per liter Standard Deviation 1.00	-1.2 International units per liter Standard Deviation 2.17

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population. Only those participants available at the indicated time points were analyzed (represented by n= X in the category titles).

Blood samples were collected to analyze the chemistry parameters: alkaline phosphatase, alanine amino transferase, aspartate amino transferase, creatine kinase and gamma glutamyl transferase. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=2 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase Alkaline phosphatase, n=2,4	-4.5 International units per liter Standard Deviation 0.71	-14.5 International units per liter Standard Deviation 17.41
Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase Alanine amino transferase, n=2,4	4.0 International units per liter Standard Deviation 1.41	-0.5 International units per liter Standard Deviation 3.70
Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase Aspartate amino transferase, n=2,2	2.5 International units per liter Standard Deviation 2.12	-6.5 International units per liter Standard Deviation 6.36
Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase Creatine kinase, n=2,4	-94.0 International units per liter Standard Deviation 127.28	-7.8 International units per liter Standard Deviation 20.45
Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase Gamma glutamyl transferase, n=2,3	-5.0 International units per liter Standard Deviation 1.41	-4.0 International units per liter Standard Deviation 2.65

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population.

Blood samples were collected to analyze the chemistry parameters: albumin and total protein. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Change From Baseline in Chemistry Parameters: Albumin and Total Protein Albumin	-1.3 Grams per liter Standard Deviation 1.15	-2.6 Grams per liter Standard Deviation 3.78
Period 1: Change From Baseline in Chemistry Parameters: Albumin and Total Protein Total protein	-1.7 Grams per liter Standard Deviation 2.89	-4.0 Grams per liter Standard Deviation 6.40

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.

Blood samples were collected to analyze the chemistry parameters: albumin and total protein. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=2 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: Change From Baseline in Chemistry Parameters: Albumin and Total Protein Albumin	1.5 Grams per liter Standard Deviation 0.71	-1.4 Grams per liter Standard Deviation 1.52
Period 2: Change From Baseline in Chemistry Parameters: Albumin and Total Protein Total protein	-0.5 Grams per liter Standard Deviation 0.71	-7.4 Grams per liter Standard Deviation 5.55

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles).

Blood samples were collected to analyze the chemistry parameters: direct bilirubin, total bilirubin and creatinine. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine Direct bilirubin, n=2,4	0.0 Micromoles per liter Standard Deviation 0.00	-0.5 Micromoles per liter Standard Deviation 1.73
Period 1: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine Total bilirubin, n=3,5	-3.0 Micromoles per liter Standard Deviation 1.00	-2.2 Micromoles per liter Standard Deviation 6.46
Period 1: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine Creatinine, n=3,5	-6.0 Micromoles per liter Standard Deviation 15.10	-3.6 Micromoles per liter Standard Deviation 5.59

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population. Only those participants with available at the indicated time points were analyzed (represented by n= X in the category titles).

Blood samples were collected to analyze the chemistry parameters: direct bilirubin, total bilirubin and creatinine. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine Direct bilirubin, n=1,3	2.0 Micromoles per liter Standard Deviation NA NA indicates that standard deviation could not be calculated as a single participant was analyzed.	1.3 Micromoles per liter Standard Deviation 1.53
Period 2: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine Total bilirubin, n=2,5	-2.5 Micromoles per liter Standard Deviation 0.71	-4.8 Micromoles per liter Standard Deviation 4.02
Period 2: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine Creatinine, n=2,5	-5.0 Micromoles per liter Standard Deviation 16.97	-2.0 Micromoles per liter Standard Deviation 5.61

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles).

Blood samples were collected to analyze the chemistry parameters: calcium, glucose, potassium, sodium and blood urea nitrogen. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen Calcium, n=3,5	-0.103 Millimoles per liter Standard Deviation 0.0961	-0.024 Millimoles per liter Standard Deviation 0.1097
Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen Glucose, n=3,5	1.17 Millimoles per liter Standard Deviation 1.858	1.06 Millimoles per liter Standard Deviation 1.126
Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen Potassium, n=2,5	-0.10 Millimoles per liter Standard Deviation 0.000	-0.48 Millimoles per liter Standard Deviation 0.311
Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen Sodium, n=3,5	-2.7 Millimoles per liter Standard Deviation 1.15	-0.2 Millimoles per liter Standard Deviation 1.64
Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen Blood urea nitrogen, n=3,5	-0.27 Millimoles per liter Standard Deviation 1.234	0.14 Millimoles per liter Standard Deviation 1.174

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population. Only those participants available at the indicated time points were analyzed (represented by n= X in the category titles).

Blood samples were collected to analyze the chemistry parameters: calcium, glucose, potassium, sodium and blood urea nitrogen. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=2 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen Calcium, n=2,5	-0.125 Millimoles per liter Standard Deviation 0.0778	-0.158 Millimoles per liter Standard Deviation 0.1033
Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen Glucose, n=2,5	-0.25 Millimoles per liter Standard Deviation 0.778	-1.06 Millimoles per liter Standard Deviation 1.403
Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen Potassium, n=2,4	0.00 Millimoles per liter Standard Deviation 0.141	-0.20 Millimoles per liter Standard Deviation 0.583
Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen Sodium, n=2,5	0.5 Millimoles per liter Standard Deviation 2.12	0.4 Millimoles per liter Standard Deviation 3.36
Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen Blood urea nitrogen, n=2,5	-0.25 Millimoles per liter Standard Deviation 0.354	-0.06 Millimoles per liter Standard Deviation 0.950

PRIMARY outcome

Timeframe: Baseline (Day -1) and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population. Only those participants with available at the indicated time points were analyzed (represented by n= X in the category titles).

Urine samples were collected at indicated time points to analyze urinalysis parameters including specific gravity, potential of hydrogen, glucose, protein, blood and ketones by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as positive, Trace, 1+, 2+, 3+ and 4+, indicating proportional concentrations in the urine sample. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Only categories with abnormal urinalysis values are presented.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick Urine occult blood- Baseline, 1+: n=3,5	0 Participants	1 Participants
Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick Urine occult blood- 24 hours, Trace: n=3,4	0 Participants	1 Participants
Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick Urine occult blood- 24 hours, 1+: n=3,4	0 Participants	1 Participants
Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick Urine protein- Baseline, 1+: n=3,4	1 Participants	0 Participants
Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick Urine protein - 24 hours, 1+: n=3,4	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Baseline (Day -1), 24 hours post-GSK3008348 dose and Day 15 (follow-up)

Population: Intent-to-Treat Population. Only those participants with available at the indicated time points were analyzed (represented by n= X in the category titles).

Urine samples were collected at indicated time points to analyze urinalysis parameters including specific gravity, potential of hydrogen, glucose, protein, blood and ketones by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as positive, Trace, 1+, 2+, 3+ and 4+, indicating proportional concentrations in the urine sample. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Only categories with abnormal urinalysis values are presented.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick Urine occult blood- Baseline, Trace: n=2,5	0 Participants	1 Participants
Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick Urine occult blood- Day 15, Trace: n=3,5	0 Participants	1 Participants
Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick Urine glucose- 24 hours, 100 mg/dL : n=2,5	0 Participants	1 Participants
Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick Urine ketones - 24 hours, 5mg/dL: n=3,4	0 Participants	2 Participants
Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick Urine proteins- Baseline, Trace: n=2,5	0 Participants	1 Participants
Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick Urine proteins- 24 hours, Trace: n=2,5	0 Participants	1 Participants
Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick Urine proteins- Day 15, Trace: n=3,5	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Baseline (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population.

SBP and DBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP- 0.5 hours	3.3 Millimeters of mercury Standard Deviation 9.29	2.4 Millimeters of mercury Standard Deviation 9.91
Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP- 2 hours	1.3 Millimeters of mercury Standard Deviation 1.15	-0.6 Millimeters of mercury Standard Deviation 3.21
Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP- 4 hours	-7.0 Millimeters of mercury Standard Deviation 5.29	0.2 Millimeters of mercury Standard Deviation 6.80
Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP- 8 hours	-0.7 Millimeters of mercury Standard Deviation 9.29	1.4 Millimeters of mercury Standard Deviation 10.36
Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP- 24 hours	-5.7 Millimeters of mercury Standard Deviation 5.51	-4.4 Millimeters of mercury Standard Deviation 6.31
Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP- 0.5 hours	16.3 Millimeters of mercury Standard Deviation 24.17	2.2 Millimeters of mercury Standard Deviation 20.07
Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP- 2 hours	5.0 Millimeters of mercury Standard Deviation 3.61	-11.0 Millimeters of mercury Standard Deviation 4.36
Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP- 4 hours	-1.7 Millimeters of mercury Standard Deviation 4.73	-4.8 Millimeters of mercury Standard Deviation 14.75
Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP- 8 hours	12.0 Millimeters of mercury Standard Deviation 23.90	1.8 Millimeters of mercury Standard Deviation 16.53
Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP- 24 hours	1.3 Millimeters of mercury Standard Deviation 11.59	-5.0 Millimeters of mercury Standard Deviation 12.51

PRIMARY outcome

Timeframe: Baseline (Day -1), 30 minutes (post-PET scan), Day 1 (prior to discharge) and Day 2 (pre-PET scan)

Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.

SBP and DBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=2 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: Change From Baseline in Vital Signs: DBP and SBP DBP-30 minutes post-PET scan	17.0 Millimeter of mercury Standard Deviation 12.73	4.2 Millimeter of mercury Standard Deviation 6.91
Period 2: Change From Baseline in Vital Signs: DBP and SBP DBP- Day 1 prior to discharge	10.0 Millimeter of mercury Standard Deviation 14.14	-3.6 Millimeter of mercury Standard Deviation 8.05
Period 2: Change From Baseline in Vital Signs: DBP and SBP DBP- Day 2 pre-PET scan	7.5 Millimeter of mercury Standard Deviation 20.51	-4.8 Millimeter of mercury Standard Deviation 4.44
Period 2: Change From Baseline in Vital Signs: DBP and SBP SBP- 30 minutes post-PET scan	13.5 Millimeter of mercury Standard Deviation 20.51	7.2 Millimeter of mercury Standard Deviation 7.89
Period 2: Change From Baseline in Vital Signs: DBP and SBP SBP- Day 1 prior to discharge	10.0 Millimeter of mercury Standard Deviation 12.73	-6.0 Millimeter of mercury Standard Deviation 12.19
Period 2: Change From Baseline in Vital Signs: DBP and SBP SBP- Day 2 pre-PET scan	-3.0 Millimeter of mercury Standard Deviation 19.80	-8.6 Millimeter of mercury Standard Deviation 16.56

PRIMARY outcome

Timeframe: Baseline (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population.

Heart rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Change From Baseline in Vital Signs: Heart Rate 0.5 hours	-0.3 Beats per minute Standard Deviation 9.29	-7.0 Beats per minute Standard Deviation 11.11
Period 1: Change From Baseline in Vital Signs: Heart Rate 2 hours	4.0 Beats per minute Standard Deviation 4.58	-3.0 Beats per minute Standard Deviation 10.49
Period 1: Change From Baseline in Vital Signs: Heart Rate 4 hours	12.3 Beats per minute Standard Deviation 9.81	-2.4 Beats per minute Standard Deviation 6.23
Period 1: Change From Baseline in Vital Signs: Heart Rate 8 hours	17.3 Beats per minute Standard Deviation 2.08	-1.4 Beats per minute Standard Deviation 10.11
Period 1: Change From Baseline in Vital Signs: Heart Rate 24 hours	6.7 Beats per minute Standard Deviation 3.51	0.8 Beats per minute Standard Deviation 5.93

PRIMARY outcome

Timeframe: Baseline (Day -1), 30 minutes (post-PET scan), Day 1 (prior to discharge) and Day 2 (pre-PET scan)

Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.

Heart rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=2 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: Change From Baseline in Vital Signs: Heart Rate 30 minutes post-PET scan	-5.5 Beats per minute Standard Deviation 6.36	-10.2 Beats per minute Standard Deviation 3.77
Period 2: Change From Baseline in Vital Signs: Heart Rate Day 1 prior to discharge	3.0 Beats per minute Standard Deviation 4.24	-5.0 Beats per minute Standard Deviation 6.78
Period 2: Change From Baseline in Vital Signs: Heart Rate Day 2 pre-PET scan	-5.5 Beats per minute Standard Deviation 13.44	-9.8 Beats per minute Standard Deviation 4.97

PRIMARY outcome

Timeframe: Baseline (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population.

Respiration rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Change From Baseline in Vital Sign: Respiration Rate 0.5 hours	-0.3 Breaths per minute Standard Deviation 1.53	1.2 Breaths per minute Standard Deviation 2.17
Period 1: Change From Baseline in Vital Sign: Respiration Rate 2 hours	1.0 Breaths per minute Standard Deviation 1.00	2.8 Breaths per minute Standard Deviation 3.70
Period 1: Change From Baseline in Vital Sign: Respiration Rate 4 hours	1.0 Breaths per minute Standard Deviation 1.00	1.6 Breaths per minute Standard Deviation 2.19
Period 1: Change From Baseline in Vital Sign: Respiration Rate 8 hours	0.3 Breaths per minute Standard Deviation 0.58	2.2 Breaths per minute Standard Deviation 3.56
Period 1: Change From Baseline in Vital Sign: Respiration Rate 24 hours	-0.7 Breaths per minute Standard Deviation 1.15	1.0 Breaths per minute Standard Deviation 2.00

PRIMARY outcome

Timeframe: Baseline (Day -1), 30 minutes (post-PET scan), Day 1 (prior to discharge) and Day 2 (pre-PET scan)

Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.

Respiration rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=2 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: Change From Baseline in Vital Sign: Respiration Rate 30 minutes post-PET scan	0.0 Breaths per minute Standard Deviation 2.83	0.0 Breaths per minute Standard Deviation 0.00
Period 2: Change From Baseline in Vital Sign: Respiration Rate Day 1 prior to discharge	0.0 Breaths per minute Standard Deviation 2.83	2.8 Breaths per minute Standard Deviation 1.10
Period 2: Change From Baseline in Vital Sign: Respiration Rate Day 2 pre-PET scan	-0.5 Breaths per minute Standard Deviation 0.71	1.0 Breaths per minute Standard Deviation 2.24

PRIMARY outcome

Timeframe: Baseline (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population.

Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Change From Baseline in Vital Sign: Temperature 0.5 hours	0.27 Celsius Standard Deviation 0.231	0.0 Celsius Standard Deviation 0.346
Period 1: Change From Baseline in Vital Sign: Temperature 2 hours	0.30 Celsius Standard Deviation 0.656	0.00 Celsius Standard Deviation 0.265
Period 1: Change From Baseline in Vital Sign: Temperature 4 hours	0.20 Celsius Standard Deviation 0.265	-0.02 Celsius Standard Deviation 0.327
Period 1: Change From Baseline in Vital Sign: Temperature 8 hours	0.43 Celsius Standard Deviation 0.289	0.28 Celsius Standard Deviation 0.319
Period 1: Change From Baseline in Vital Sign: Temperature 24 hours	0.60 Celsius Standard Deviation 0.361	0.10 Celsius Standard Deviation 0.292

PRIMARY outcome

Timeframe: Baseline (Day -1), 30 minutes (post-PET scan), Day 1 (prior to discharge) and Day 2 (pre-PET scan)

Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.

Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=2 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: Change From Baseline in Vital Sign: Temperature 30 minutes post-PET scan	-0.25 Celcius Standard Deviation 0.919	0.06 Celcius Standard Deviation 0.537
Period 2: Change From Baseline in Vital Sign: Temperature Day 1 prior to discharge	-0.05 Celcius Standard Deviation 0.778	0.34 Celcius Standard Deviation 0.786
Period 2: Change From Baseline in Vital Sign: Temperature Day 2 pre-PET scan	-0.35 Celcius Standard Deviation 1.061	0.06 Celcius Standard Deviation 0.518

PRIMARY outcome

Timeframe: Pre-dose (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population.

Triplicate 12-lead ECG were obtained to measure ECG parameters. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters Pre-dose measurement 1, NCS	2 Participants	4 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters Pre-dose measurement 1, CS	0 Participants	0 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters Pre-dose measurement 2, NCS	2 Participants	3 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters Pre-dose measurement 2, CS	0 Participants	0 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters Pre-dose measurement 3, NCS	3 Participants	3 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters Pre-dose measurement 3, CS	0 Participants	0 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 0.5 hours measurement 1, NCS	2 Participants	4 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 0.5 hours measurement 1, CS	0 Participants	0 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 0.5 hours measurement 2, NCS	3 Participants	4 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 0.5 hours measurement 2, CS	0 Participants	0 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 0.5 hours measurement 3, NCS	3 Participants	4 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 0.5 hours measurement 3, CS	0 Participants	0 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 2 hours measurement 1, NCS	3 Participants	3 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 2 hours measurement 1, CS	0 Participants	0 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 2 hours measurement 2, NCS	3 Participants	3 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 2 hours measurement 2, CS	0 Participants	0 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 2 hours measurement 3, NCS	3 Participants	3 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 2 hours measurement 3, CS	0 Participants	0 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 4 hours measurement 1, NCS	3 Participants	4 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 4 hours measurement 1, CS	0 Participants	0 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 4 hours measurement 2, NCS	3 Participants	4 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 4 hours measurement 2, CS	0 Participants	0 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 4 hours measurement 3, NCS	3 Participants	4 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 4 hours measurement 3, CS	0 Participants	0 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 8 hours measurement 1, NCS	3 Participants	4 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 8 hours measurement 1, CS	0 Participants	0 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 8 hours measurement 2, NCS	3 Participants	4 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 8 hours measurement 2, CS	0 Participants	0 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 8 hours measurement 3, NCS	3 Participants	4 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 8 hours measurement 3, CS	0 Participants	0 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 24 hours measurement 1, NCS	3 Participants	4 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 24 hours measurement 1, CS	0 Participants	0 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 24 hours measurement 2, NCS	3 Participants	4 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 24 hours measurement 2, CS	0 Participants	0 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 24 hours measurement 3, NCS	2 Participants	4 Participants
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters 24 hours measurement 3, CS	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Pre-dose (Day -1), 30 minutes (post-PET scan), Day 1 (prior to discharge), Day 2 (pre-PET scan) and Day 15 (follow-up)

Population: Intent-to-Treat Population. Only those participants with available at the indicated time points were analyzed (represented by n= X in the category titles).

Triplicate 12-lead ECG were obtained to measure ECG parameters. Abnormal findings were categorized as CS and NCS. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Pre-dose measurement 1, NCS,n=2,5	0 Participants	5 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Pre-dose measurement 1, CS,n=2,5	0 Participants	0 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Pre-dose measurement 2, NCS,n=2,5	0 Participants	5 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Pre-dose measurement 2, CS,n=2,5	0 Participants	0 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Pre-dose measurement 3, NCS,n=2,5	0 Participants	5 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Pre-dose measurement 3, CS,n=2,5	0 Participants	0 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters 30 minutes measurement 1, NCS,n=2,5	1 Participants	4 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters 30 minutes measurement 1, CS,n=2,5	0 Participants	0 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters 30 minutes measurement 2, NCS,n=2,5	1 Participants	4 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters 30 minutes measurement 2, CS,n=2,5	0 Participants	0 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters 30 minutes measurement 3, NCS,n=2,5	1 Participants	4 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters 30 minutes measurement 3, CS,n=2,5	0 Participants	0 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Day 1 measurement 1, NCS,n=2,5	1 Participants	4 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Day 1 measurement 1, CS,n=2,5	0 Participants	0 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Day 1 measurement 2, NCS,n=2,5	1 Participants	4 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Day 1 measurement 2, CS,n=2,5	0 Participants	0 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Day 1 measurement 3, NCS,n=2,5	1 Participants	4 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Day 1 measurement 3, CS,n=2,5	0 Participants	0 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Day 2 measurement 1, NCS,n=2,5	2 Participants	3 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Day 2 measurement 1, CS,n=2,5	0 Participants	0 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Day 2 measurement 2, NCS,n=2,5	2 Participants	3 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Day 2 measurement 2, CS,n=2,5	0 Participants	0 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Day 2 measurement 3, NCS,n=2,5	2 Participants	4 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Day 2 measurement 3, CS,n=2,5	0 Participants	0 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Day 15 measurement 1, NCS,n=3,5	1 Participants	3 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Day 15 measurement 1, CS,n=3,5	0 Participants	0 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Day 15 measurement 2, NCS,n=3,5	0 Participants	3 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Day 15 measurement 2, CS,n=3,5	0 Participants	0 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Day 15 measurement 3, NCS,n=3,5	1 Participants	3 Participants
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters Day 15 measurement 3, CS,n=3,5	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day -1), 1 hour and 24 hours post-GSK3008348 dose

Population: Intent-to-Treat Population.

FEV1 and FVC is a measure of lung function and the maximal amount of air that can be forcefully exhaled in one second. FEV1 and FVC was measured using standard spirometry equipment. Baseline was considered as the latest pre-dose assessment with a non-missing value for Baseline (Day -1). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Outcome measures

Measure	Placebo n=3 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FEV1: 1 hour	0.003 Liters Standard Deviation 0.0808	-0.058 Liters Standard Deviation 0.0881
Period 1: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FEV1: 24 hours	-0.117 Liters Standard Deviation 0.0702	-0.036 Liters Standard Deviation 0.0879
Period 1: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FVC: 1 hour	0.067 Liters Standard Deviation 0.0833	0.086 Liters Standard Deviation 0.3474
Period 1: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) FVC: 24 hours	-0.050 Liters Standard Deviation 0.1411	-0.010 Liters Standard Deviation 0.1208

SECONDARY outcome

Timeframe: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose

Population: Pharmacokinetic Population.

Blood samples were collected to evaluate the pharmacokinetics of GSK3008348 at the indicated time points. The pharmacokinetic parameters were calculated by standard non-compartmental analysis. Pharmacokinetic population consisted of all participants in the Intent-To-Treat population receiving active dose for whom a pharmacokinetic sample was analyzed.

Outcome measures

Measure	Placebo n=5 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Area Under the Plasma Concentration-time Curve From Zero Hours to Time (AUC[0-t]) After Single Dose Administration of GSK3008348	64638.3 Hours*picograms per milliliter Geometric Coefficient of Variation 58	—

SECONDARY outcome

Timeframe: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose

Population: Pharmacokinetic Population.

Blood samples were collected to evaluate the pharmacokinetics of GSK3008348 at the indicated time points. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Outcome measures

Measure	Placebo n=5 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: AUC(0-t) After Single Dose Administration of GSK3008348	66122.5 Hours*picogram per milliliter Geometric Coefficient of Variation 44	—

SECONDARY outcome

Timeframe: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose

Population: Pharmacokinetic Population. Only those participants with data available at the indicated data points were analyzed.

Blood samples were collected to evaluate the pharmacokinetics of GSK3008348 at the indicated time points. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Outcome measures

Measure	Placebo n=4 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Area Under the Plasma Concentration-time Curve From Zero Hours to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3008348	67715.8 Hours*picograms per milliliter Geometric Coefficient of Variation 80	—

SECONDARY outcome

Timeframe: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose

Population: Pharmacokinetic Population. Data were not analyzed for AUC(0-infinity) as there were not enough data points collected for a terminal slope required to calculate AUC(0-infinity).

Blood samples were collected to evaluate the pharmacokinetics of GSK3008348 at the indicated time points. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose

Population: Pharmacokinetic Population.

Blood samples were collected to evaluate the pharmacokinetics of GSK3008348 at the indicated time points. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Outcome measures

Measure	Placebo n=5 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3008348	14050.4 Picograms per milliliter Geometric Coefficient of Variation 38	—

SECONDARY outcome

Timeframe: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose

Population: Pharmacokinetic Population.

Blood samples were collected to evaluate the pharmacokinetics of GSK3008348 at the indicated time points. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Outcome measures

Measure	Placebo n=5 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: Cmax After Single Dose Administration of GSK3008348	10418.2 Picograms per milliliter Geometric Coefficient of Variation 31	—

SECONDARY outcome

Timeframe: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose

Population: Pharmacokinetic Population.

Blood samples were collected to evaluate the pharmacokinetics of GSK3008348 at the indicated time points. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Outcome measures

Measure	Placebo n=5 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Time of Occurrence of Cmax (Tmax) After Single Dose Administration of GSK3008348	0.50 Hours Interval 0.4 to 0.5	—

SECONDARY outcome

Timeframe: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose

Population: Pharmacokinetic Population.

Blood samples were collected to evaluate the pharmacokinetics of GSK3008348 at the indicated time points. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Outcome measures

Measure	Placebo n=5 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: Tmax After Single Dose Administration of GSK3008348	0.47 Hours Interval 0.4 to 0.5	—

SECONDARY outcome

Timeframe: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose

Population: Pharmacokinetic Population.

Blood samples were collected to evaluate the pharmacokinetics of GSK3008348 at the indicated time points. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Outcome measures

Measure	Placebo n=5 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 1: Terminal Phase Half-life (t1/2) After Single Dose Administration of GSK3008348	10.6 Hours Geometric Coefficient of Variation 21	—

SECONDARY outcome

Timeframe: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose

Population: Pharmacokinetic Population. Data were not analyzed for t1/2 as there were not enough data points collected for a terminal slope required to calculate t1/2.

Blood samples were collected to evaluate the pharmacokinetics of GSK3008348 at the indicated time points. The pharmacokinetic parameters were calculated by standard non-compartmental analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (pre-dose) and 24 hours post-dose PET scan 2

Population: Per-Protocol Population. Only those participants with PET data available at the indicated time points were analyzed (represented by n= X in the category titles).

The changes in the uptake of [18F]-FBA-A20FMDV2 in the whole lung, assessed by VT derived from kinetic analysis of the dynamic PET data was used to evaluate target engagement in the lung after single nebulized doses of GSK3008348

Outcome measures

Measure	Placebo n=2 Participants Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 Participants Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Period 2: VT of [18F]-FBAA20FMDV2 in the Whole Lung (Not Corrected for Air Volume) Approximately 24 Hours Post-dose Compared to Pre-dose Baseline, n=2,5	1.664 mL/cm^3 Geometric Coefficient of Variation 19.67	1.503 mL/cm^3 Geometric Coefficient of Variation 37.32
Period 2: VT of [18F]-FBAA20FMDV2 in the Whole Lung (Not Corrected for Air Volume) Approximately 24 Hours Post-dose Compared to Pre-dose 24 hours post-dose PET scan 2, n=1,3	1.530 mL/cm^3 Geometric Coefficient of Variation NA NA indicates that geometric coefficient of variation was not calculated as there was only one data point.	1.474 mL/cm^3 Geometric Coefficient of Variation 24.43

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

GSK3008348 1000 mcg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=3 participants at risk Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.	GSK3008348 1000 mcg n=5 participants at risk Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2.
Gastrointestinal disorders Diarrhoea	33.3% 1/3 • Number of events 1 • AEs and SAEs were collected from Day 1 up to 62 days Intent-to-Treat population was used to assess AEs and SAEs.	0.00% 0/5 • AEs and SAEs were collected from Day 1 up to 62 days Intent-to-Treat population was used to assess AEs and SAEs.
Infections and infestations Urinary tract infection	0.00% 0/3 • AEs and SAEs were collected from Day 1 up to 62 days Intent-to-Treat population was used to assess AEs and SAEs.	20.0% 1/5 • Number of events 1 • AEs and SAEs were collected from Day 1 up to 62 days Intent-to-Treat population was used to assess AEs and SAEs.
Nervous system disorders Headache	0.00% 0/3 • AEs and SAEs were collected from Day 1 up to 62 days Intent-to-Treat population was used to assess AEs and SAEs.	20.0% 1/5 • Number of events 1 • AEs and SAEs were collected from Day 1 up to 62 days Intent-to-Treat population was used to assess AEs and SAEs.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/3 • AEs and SAEs were collected from Day 1 up to 62 days Intent-to-Treat population was used to assess AEs and SAEs.	20.0% 1/5 • Number of events 1 • AEs and SAEs were collected from Day 1 up to 62 days Intent-to-Treat population was used to assess AEs and SAEs.
Surgical and medical procedures Tooth extraction	0.00% 0/3 • AEs and SAEs were collected from Day 1 up to 62 days Intent-to-Treat population was used to assess AEs and SAEs.	20.0% 1/5 • Number of events 1 • AEs and SAEs were collected from Day 1 up to 62 days Intent-to-Treat population was used to assess AEs and SAEs.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: GSKClinicalSupportHD@gsk.com

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER