A Phase 1 interventional study of GSK3008348 and Placebo in Idiopathic Pulmonary Fibrosis, sponsored by GlaxoSmithKline. Terminated at 3 sites in United Kingdom. Open to participants aged 50 Years and older. Per ClinicalTrials.gov, last updated 2019-08-12.
Sponsored by GlaxoSmithKline · Phase 1, Interventional, and Treatment
GSK3008348 is being developed as a treatment for IPF. A first-time-in-human study showed that single nebulized doses of 1-3000 micrograms (mcg) GSK3008348 in healthy volunteers were well tolerated, with pharmacokinetic (PK) exposures within the defined limits set in the protocol. The proposed study is a 2-cohort study of single doses, intended to evaluate the safety, tolerability and PK of the drug in participants with IPF not currently treated with pirfenidone or nintedanib, and to obtain preliminary information on target engagement. Cohort 1 will be a 2-period, randomized, double-blind, placebo-controlled group with at least 7 days washout between doses, and follow-up period of up to 7-14 days. Cohort 2 is optional. It will be designed to further explore safety and to provide additional information on the target engagement profile of GSK3008348. The total duration of the study will be up to 62 days.
680 studies on the registry are indexed under Pulmonary Fibrosis; 119 are open to participants now.
This study's enrollment of 8 is below the median of 50 across 419 interventional studies indexed under Pulmonary Fibrosis.
Browse Pulmonary Fibrosis studies →GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.
Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.
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Exclusion Criteria:
Note: participants with a positive Hepatitis C antibody test because of previous, resolved disease can be enrolled if a confirmatory negative Hepatitis C Ribonucleic Acid (RNA) test is obtained.
Participants will receive a single nebulized dose of GSK3008348 during each of 2 planned dosing periods and up to 3 microdose administrations of \[18F\]-FBA-A20FMDV2 for the PET scanning in period 2.
Drug: GSK3008348 · Drug: [18F]-FBA-A20FMDV2
Participants will receive a single nebulized dose of placebo during each of 2 planned dosing periods and up to 3 microdose of \[18F\]-FBA-A20FMDV2 for the PET scanning in period 2.
Drug: Placebo · Drug: [18F]-FBA-A20FMDV2
Participants will receive a single nebulized dose of GSK3008348 during each of 2 planned dosing periods and up to 3 microdose administrations of \[18F\]-FBA-A20FMDV2 for the PET scanning in period 2.
Drug: GSK3008348 · Drug: [18F]-FBA-A20FMDV2
Participants will receive a single nebulized dose of placebo during each of 2 planned dosing periods and up to 3 microdose of \[18F\]-FBA-A20FMDV2 for the PET scanning in period 2.
Drug: Placebo · Drug: [18F]-FBA-A20FMDV2
Solution for nebulisation. Available as clear colorless to pale yellow colored solution in a 5mL vial with 20 millimeter (mm) stopper and aluminium seal yellow colored solution in a 5mL vial with 20 millimeter (mm) stopper and aluminium seal.
Solution for nebulisation. Available as clear colorless to pale yellow colored solution in a 5mL vial with 20mm stopper and aluminium seal.
Radio-labeled peptide ligand for PET scan. Available as intravenous (IV) infusion, 20 mL.
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
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.
Time frame: Baseline (pre-dose) and 30 minutes post-dose
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: Up to 62 days
Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 1: Change From Baseline in Hematology Parameter: Hemoglobin
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 2: Change From Baseline in Hematology Parameter: Hemoglobin
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 1: Change From Baseline in Hematology Parameter: Hematocrit
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 2: Change From Baseline in Hematology Parameter: Hematocrit
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 1: Change From Baseline in Hematology Parameter: Red Blood Cell Count
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 2: Change From Baseline in Hematology Parameter: Red Blood Cell Count
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 1: Change From Baseline in Chemistry Parameters: Albumin and Total Protein
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 2: Change From Baseline in Chemistry Parameters: Albumin and Total Protein
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 1: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 2: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick
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.
Time frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose
Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick
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.
Time frame: Baseline (Day -1), 24 hours post-GSK3008348 dose and Day 15 (follow-up)
Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
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.
Time frame: Baseline (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose
Period 2: Change From Baseline in Vital Signs: DBP and SBP
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.
Time frame: Baseline (Day -1), 30 minutes (post-PET scan), Day 1 (prior to discharge) and Day 2 (pre-PET scan)
Period 1: Change From Baseline in Vital Signs: Heart Rate
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.
Time frame: Baseline (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose
Period 2: Change From Baseline in Vital Signs: Heart Rate
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.
Time frame: Baseline (Day -1), 30 minutes (post-PET scan), Day 1 (prior to discharge) and Day 2 (pre-PET scan)
Period 1: Change From Baseline in Vital Sign: Respiration Rate
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.
Time frame: Baseline (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose
Period 2: Change From Baseline in Vital Sign: Respiration Rate
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.
Time frame: Baseline (Day -1), 30 minutes (post-PET scan), Day 1 (prior to discharge) and Day 2 (pre-PET scan)
Period 1: Change From Baseline in Vital Sign: Temperature
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.
Time frame: Baseline (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose
Period 2: Change From Baseline in Vital Sign: Temperature
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.
Time frame: Baseline (Day -1), 30 minutes (post-PET scan), Day 1 (prior to discharge) and Day 2 (pre-PET scan)
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters
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.
Time frame: Pre-dose (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters
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.
Time frame: Pre-dose (Day -1), 30 minutes (post-PET scan), Day 1 (prior to discharge), Day 2 (pre-PET scan) and Day 15 (follow-up)
Period 1: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC)
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.
Time frame: Baseline (Day -1), 1 hour and 24 hours post-GSK3008348 dose
Period 1: Area Under the Plasma Concentration-time Curve From Zero Hours to Time (AUC[0-t]) After Single Dose Administration of GSK3008348
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.
Time frame: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose
Period 2: AUC(0-t) After Single Dose Administration of GSK3008348
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.
Time frame: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose
Period 1: Area Under the Plasma Concentration-time Curve From Zero Hours to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3008348
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.
Time frame: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose
Period 2: AUC(0-infinity) After Single Dose Administration of GSK3008348
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.
Time frame: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose
Period 1: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3008348
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.
Time frame: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose
Period 2: Cmax After Single Dose Administration of GSK3008348
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.
Time frame: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose
Period 1: Time of Occurrence of Cmax (Tmax) After Single Dose Administration of GSK3008348
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.
Time frame: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose
Period 2: Tmax After Single Dose Administration of GSK3008348
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.
Time frame: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose
Period 1: Terminal Phase Half-life (t1/2) After Single Dose Administration of GSK3008348
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.
Time frame: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose
Period 2: t1/2 After Single Dose Administration of GSK3008348
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.
Time frame: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose
Period 2: VT of [18F]-FBAA20FMDV2 in the Whole Lung (Not Corrected for Air Volume) Approximately 24 Hours Post-dose Compared to Pre-dose
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
Time frame: Baseline (pre-dose) and 24 hours post-dose PET scan 2
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.
| Milestone | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Started | 3 | 5 |
| Completed | 3 | 5 |
| Not completed | 0 | 0 |
| Milestone | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Started | 3 | 5 |
| Completed | 3 | 5 |
| Not completed | 0 | 0 |
| Milestone | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Started | 3 | 5 |
| Completed | 2 | 5 |
| Not completed | 1 | 0 |
| Withdrew: Protocol-defined stop criteria reached | 1 | 0 |
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.
| Milliliter per cubic centimeter(mL/cm^3) | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Baseline | 1.664 ± 19.67 | 1.503 ± 37.32 |
| 30 minutes post-dose PET scan 1 | 1.572 ± 8.56 | 1.198 ± 44.37 |
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.
| Participants | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| AEs | 1 | 3 |
| SAEs | 0 | 0 |
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.
| Giga cells per liter | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Basophils | 0.000 ± 0.0000 | -0.008 ± 0.0179 |
| Eosinophils | 0.000 ± 0.0000 | 0.018 ± 0.0402 |
| Lymphocytes | 0.267 ± 0.0577 | -0.086 ± 0.3361 |
| Monocytes | -0.033 ± 0.0577 | -0.106 ± 0.1232 |
| Total neutrophils | 0.300 ± 0.5292 | -0.762 ± 0.8135 |
| Platelet count | -3.0 ± 16.46 | -24.2 ± 11.69 |
| WBC count | 0.467 ± 0.4933 | -0.982 ± 0.9509 |
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.
| Giga cells per liter | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Basophils | 0.010 ± 0.0424 | -0.034 ± 0.0365 |
| Eosinophils | 0.025 ± 0.0071 | -0.030 ± 0.1051 |
| Lymphocytes | 0.485 ± 0.1061 | 0.168 ± 0.3269 |
| Monocytes | -0.050 ± 0.1414 | -0.046 ± 0.1172 |
| Total neutrophils | -0.155 ± 0.5728 | -0.866 ± 0.6179 |
| Platelet count | -2.5 ± 16.26 | 15.8 ± 12.87 |
| WBC count | 0.270 ± 0.5657 | -0.748 ± 0.7351 |
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.
| Grams per liter | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Period 1: Change From Baseline in Hematology Parameter: Hemoglobin | -4.3 ± 2.89 | -4.4 ± 6.84 |
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.
| Grams per liter | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Period 2: Change From Baseline in Hematology Parameter: Hemoglobin | -4.0 ± 5.66 | -8.8 ± 3.56 |
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.
| Proportion of red blood cells in blood | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Period 1: Change From Baseline in Hematology Parameter: Hematocrit | 0.000 ± 0.0000 | -0.016 ± 0.0270 |
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.
| Proportion of red blood cells in blood | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Period 2: Change From Baseline in Hematology Parameter: Hematocrit | -0.013 ± 0.0057 | -0.028 ± 0.0141 |
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.
| Picrograms | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Period 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin | -0.30 ± 0.265 | 0.10 ± 0.500 |
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.
| Picrograms | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Period 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin | -0.75 ± 0.212 | -0.50 ± 0.361 |
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.
| Femtoliters | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Period 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume | 1.00 ± 1.000 | -0.58 ± 1.559 |
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.
| Femtoliters | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Period 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume | -2.35 ± 1.061 | -1.62 ± 1.213 |
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.
| Trillion cells per liter | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Period 1: Change From Baseline in Hematology Parameter: Red Blood Cell Count | -0.093 ± 0.0702 | -0.168 ± 0.2946 |
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.
| Trillion cells per liter | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Period 2: Change From Baseline in Hematology Parameter: Red Blood Cell Count | -0.010 ± 0.1556 | -0.226 ± 0.1372 |
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.
| International units per liter | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Alkaline phosphatase, n=3,5 | -1.7 ± 1.53 | -3.4 ± 10.43 |
| Alanine amino transferase, n=3,5 | 1.3 ± 1.53 | -0.6 ± 1.14 |
| Aspartate amino transferase, n=2,3 | 0.0 ± 2.83 | -0.3 ± 3.06 |
| Creatine kinase, n=3,5 | -95.0 ± 76.62 | -13.8 ± 9.31 |
| Gamma glutamyl transferase, n=3,5 | -1.0 ± 1.00 | -1.2 ± 2.17 |
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.
| International units per liter | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Alkaline phosphatase, n=2,4 | -4.5 ± 0.71 | -14.5 ± 17.41 |
| Alanine amino transferase, n=2,4 | 4.0 ± 1.41 | -0.5 ± 3.70 |
| Aspartate amino transferase, n=2,2 | 2.5 ± 2.12 | -6.5 ± 6.36 |
| Creatine kinase, n=2,4 | -94.0 ± 127.28 | -7.8 ± 20.45 |
| Gamma glutamyl transferase, n=2,3 | -5.0 ± 1.41 | -4.0 ± 2.65 |
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.
| Grams per liter | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Albumin | -1.3 ± 1.15 | -2.6 ± 3.78 |
| Total protein | -1.7 ± 2.89 | -4.0 ± 6.40 |
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.
| Grams per liter | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Albumin | 1.5 ± 0.71 | -1.4 ± 1.52 |
| Total protein | -0.5 ± 0.71 | -7.4 ± 5.55 |
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.
| Micromoles per liter | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Direct bilirubin, n=2,4 | 0.0 ± 0.00 | -0.5 ± 1.73 |
| Total bilirubin, n=3,5 | -3.0 ± 1.00 | -2.2 ± 6.46 |
| Creatinine, n=3,5 | -6.0 ± 15.10 | -3.6 ± 5.59 |
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.
| Micromoles per liter | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Direct bilirubin, n=1,3 | 2.0 ± NA | 1.3 ± 1.53 |
| Total bilirubin, n=2,5 | -2.5 ± 0.71 | -4.8 ± 4.02 |
| Creatinine, n=2,5 | -5.0 ± 16.97 | -2.0 ± 5.61 |
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.
| Millimoles per liter | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Calcium, n=3,5 | -0.103 ± 0.0961 | -0.024 ± 0.1097 |
| Glucose, n=3,5 | 1.17 ± 1.858 | 1.06 ± 1.126 |
| Potassium, n=2,5 | -0.10 ± 0.000 | -0.48 ± 0.311 |
| Sodium, n=3,5 | -2.7 ± 1.15 | -0.2 ± 1.64 |
| Blood urea nitrogen, n=3,5 | -0.27 ± 1.234 | 0.14 ± 1.174 |
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.
| Millimoles per liter | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Calcium, n=2,5 | -0.125 ± 0.0778 | -0.158 ± 0.1033 |
| Glucose, n=2,5 | -0.25 ± 0.778 | -1.06 ± 1.403 |
| Potassium, n=2,4 | 0.00 ± 0.141 | -0.20 ± 0.583 |
| Sodium, n=2,5 | 0.5 ± 2.12 | 0.4 ± 3.36 |
| Blood urea nitrogen, n=2,5 | -0.25 ± 0.354 | -0.06 ± 0.950 |
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.
| Participants | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Urine occult blood- Baseline, 1+: n=3,5 | 0 | 1 |
| Urine occult blood- 24 hours, Trace: n=3,4 | 0 | 1 |
| Urine occult blood- 24 hours, 1+: n=3,4 | 0 | 1 |
| Urine protein- Baseline, 1+: n=3,4 | 1 | 0 |
| Urine protein - 24 hours, 1+: n=3,4 | 0 | 1 |
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.
| Participants | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Urine occult blood- Baseline, Trace: n=2,5 | 0 | 1 |
| Urine occult blood- Day 15, Trace: n=3,5 | 0 | 1 |
| Urine glucose- 24 hours, 100 mg/dL : n=2,5 | 0 | 1 |
| Urine ketones - 24 hours, 5mg/dL: n=3,4 | 0 | 2 |
| Urine proteins- Baseline, Trace: n=2,5 | 0 | 1 |
| Urine proteins- 24 hours, Trace: n=2,5 | 0 | 1 |
| Urine proteins- Day 15, Trace: n=3,5 | 0 | 1 |
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.
| Millimeters of mercury | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| DBP- 0.5 hours | 3.3 ± 9.29 | 2.4 ± 9.91 |
| DBP- 2 hours | 1.3 ± 1.15 | -0.6 ± 3.21 |
| DBP- 4 hours | -7.0 ± 5.29 | 0.2 ± 6.80 |
| DBP- 8 hours | -0.7 ± 9.29 | 1.4 ± 10.36 |
| DBP- 24 hours | -5.7 ± 5.51 | -4.4 ± 6.31 |
| SBP- 0.5 hours | 16.3 ± 24.17 | 2.2 ± 20.07 |
| SBP- 2 hours | 5.0 ± 3.61 | -11.0 ± 4.36 |
| SBP- 4 hours | -1.7 ± 4.73 | -4.8 ± 14.75 |
| SBP- 8 hours | 12.0 ± 23.90 | 1.8 ± 16.53 |
| SBP- 24 hours | 1.3 ± 11.59 | -5.0 ± 12.51 |
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.
| Millimeter of mercury | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| DBP-30 minutes post-PET scan | 17.0 ± 12.73 | 4.2 ± 6.91 |
| DBP- Day 1 prior to discharge | 10.0 ± 14.14 | -3.6 ± 8.05 |
| DBP- Day 2 pre-PET scan | 7.5 ± 20.51 | -4.8 ± 4.44 |
| SBP- 30 minutes post-PET scan | 13.5 ± 20.51 | 7.2 ± 7.89 |
| SBP- Day 1 prior to discharge | 10.0 ± 12.73 | -6.0 ± 12.19 |
| SBP- Day 2 pre-PET scan | -3.0 ± 19.80 | -8.6 ± 16.56 |
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.
| Beats per minute | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| 0.5 hours | -0.3 ± 9.29 | -7.0 ± 11.11 |
| 2 hours | 4.0 ± 4.58 | -3.0 ± 10.49 |
| 4 hours | 12.3 ± 9.81 | -2.4 ± 6.23 |
| 8 hours | 17.3 ± 2.08 | -1.4 ± 10.11 |
| 24 hours | 6.7 ± 3.51 | 0.8 ± 5.93 |
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.
| Beats per minute | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| 30 minutes post-PET scan | -5.5 ± 6.36 | -10.2 ± 3.77 |
| Day 1 prior to discharge | 3.0 ± 4.24 | -5.0 ± 6.78 |
| Day 2 pre-PET scan | -5.5 ± 13.44 | -9.8 ± 4.97 |
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.
| Breaths per minute | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| 0.5 hours | -0.3 ± 1.53 | 1.2 ± 2.17 |
| 2 hours | 1.0 ± 1.00 | 2.8 ± 3.70 |
| 4 hours | 1.0 ± 1.00 | 1.6 ± 2.19 |
| 8 hours | 0.3 ± 0.58 | 2.2 ± 3.56 |
| 24 hours | -0.7 ± 1.15 | 1.0 ± 2.00 |
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.
| Breaths per minute | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| 30 minutes post-PET scan | 0.0 ± 2.83 | 0.0 ± 0.00 |
| Day 1 prior to discharge | 0.0 ± 2.83 | 2.8 ± 1.10 |
| Day 2 pre-PET scan | -0.5 ± 0.71 | 1.0 ± 2.24 |
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.
| Celsius | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| 0.5 hours | 0.27 ± 0.231 | 0.0 ± 0.346 |
| 2 hours | 0.30 ± 0.656 | 0.00 ± 0.265 |
| 4 hours | 0.20 ± 0.265 | -0.02 ± 0.327 |
| 8 hours | 0.43 ± 0.289 | 0.28 ± 0.319 |
| 24 hours | 0.60 ± 0.361 | 0.10 ± 0.292 |
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.
| Celcius | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| 30 minutes post-PET scan | -0.25 ± 0.919 | 0.06 ± 0.537 |
| Day 1 prior to discharge | -0.05 ± 0.778 | 0.34 ± 0.786 |
| Day 2 pre-PET scan | -0.35 ± 1.061 | 0.06 ± 0.518 |
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.
| Participants | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Pre-dose measurement 1, NCS | 2 | 4 |
| Pre-dose measurement 1, CS | 0 | 0 |
| Pre-dose measurement 2, NCS | 2 | 3 |
| Pre-dose measurement 2, CS | 0 | 0 |
| Pre-dose measurement 3, NCS | 3 | 3 |
| Pre-dose measurement 3, CS | 0 | 0 |
| 0.5 hours measurement 1, NCS | 2 | 4 |
| 0.5 hours measurement 1, CS | 0 | 0 |
| 0.5 hours measurement 2, NCS | 3 | 4 |
| 0.5 hours measurement 2, CS | 0 | 0 |
| 0.5 hours measurement 3, NCS | 3 | 4 |
| 0.5 hours measurement 3, CS | 0 | 0 |
| 2 hours measurement 1, NCS | 3 | 3 |
| 2 hours measurement 1, CS | 0 | 0 |
| 2 hours measurement 2, NCS | 3 | 3 |
| 2 hours measurement 2, CS | 0 | 0 |
| 2 hours measurement 3, NCS | 3 | 3 |
| 2 hours measurement 3, CS | 0 | 0 |
| 4 hours measurement 1, NCS | 3 | 4 |
| 4 hours measurement 1, CS | 0 | 0 |
| 4 hours measurement 2, NCS | 3 | 4 |
| 4 hours measurement 2, CS | 0 | 0 |
| 4 hours measurement 3, NCS | 3 | 4 |
| 4 hours measurement 3, CS | 0 | 0 |
| 8 hours measurement 1, NCS | 3 | 4 |
| 8 hours measurement 1, CS | 0 | 0 |
| 8 hours measurement 2, NCS | 3 | 4 |
| 8 hours measurement 2, CS | 0 | 0 |
| 8 hours measurement 3, NCS | 3 | 4 |
| 8 hours measurement 3, CS | 0 | 0 |
| 24 hours measurement 1, NCS | 3 | 4 |
| 24 hours measurement 1, CS | 0 | 0 |
| 24 hours measurement 2, NCS | 3 | 4 |
| 24 hours measurement 2, CS | 0 | 0 |
| 24 hours measurement 3, NCS | 2 | 4 |
| 24 hours measurement 3, CS | 0 | 0 |
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.
| Participants | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Pre-dose measurement 1, NCS,n=2,5 | 0 | 5 |
| Pre-dose measurement 1, CS,n=2,5 | 0 | 0 |
| Pre-dose measurement 2, NCS,n=2,5 | 0 | 5 |
| Pre-dose measurement 2, CS,n=2,5 | 0 | 0 |
| Pre-dose measurement 3, NCS,n=2,5 | 0 | 5 |
| Pre-dose measurement 3, CS,n=2,5 | 0 | 0 |
| 30 minutes measurement 1, NCS,n=2,5 | 1 | 4 |
| 30 minutes measurement 1, CS,n=2,5 | 0 | 0 |
| 30 minutes measurement 2, NCS,n=2,5 | 1 | 4 |
| 30 minutes measurement 2, CS,n=2,5 | 0 | 0 |
| 30 minutes measurement 3, NCS,n=2,5 | 1 | 4 |
| 30 minutes measurement 3, CS,n=2,5 | 0 | 0 |
| Day 1 measurement 1, NCS,n=2,5 | 1 | 4 |
| Day 1 measurement 1, CS,n=2,5 | 0 | 0 |
| Day 1 measurement 2, NCS,n=2,5 | 1 | 4 |
| Day 1 measurement 2, CS,n=2,5 | 0 | 0 |
| Day 1 measurement 3, NCS,n=2,5 | 1 | 4 |
| Day 1 measurement 3, CS,n=2,5 | 0 | 0 |
| Day 2 measurement 1, NCS,n=2,5 | 2 | 3 |
| Day 2 measurement 1, CS,n=2,5 | 0 | 0 |
| Day 2 measurement 2, NCS,n=2,5 | 2 | 3 |
| Day 2 measurement 2, CS,n=2,5 | 0 | 0 |
| Day 2 measurement 3, NCS,n=2,5 | 2 | 4 |
| Day 2 measurement 3, CS,n=2,5 | 0 | 0 |
| Day 15 measurement 1, NCS,n=3,5 | 1 | 3 |
| Day 15 measurement 1, CS,n=3,5 | 0 | 0 |
| Day 15 measurement 2, NCS,n=3,5 | 0 | 3 |
| Day 15 measurement 2, CS,n=3,5 | 0 | 0 |
| Day 15 measurement 3, NCS,n=3,5 | 1 | 3 |
| Day 15 measurement 3, CS,n=3,5 | 0 | 0 |
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.
| Liters | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| FEV1: 1 hour | 0.003 ± 0.0808 | -0.058 ± 0.0881 |
| FEV1: 24 hours | -0.117 ± 0.0702 | -0.036 ± 0.0879 |
| FVC: 1 hour | 0.067 ± 0.0833 | 0.086 ± 0.3474 |
| FVC: 24 hours | -0.050 ± 0.1411 | -0.010 ± 0.1208 |
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.
| Hours*picograms per milliliter | GSK3008348 1000 mcg |
|---|---|
| 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 ± 58 |
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.
| Hours*picogram per milliliter | GSK3008348 1000 mcg |
|---|---|
| Period 2: AUC(0-t) After Single Dose Administration of GSK3008348 | 66122.5 ± 44 |
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.
| Hours*picograms per milliliter | GSK3008348 1000 mcg |
|---|---|
| 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 ± 80 |
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.
No measurements were reported for this outcome.
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.
| Picograms per milliliter | GSK3008348 1000 mcg |
|---|---|
| Period 1: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3008348 | 14050.4 ± 38 |
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.
| Picograms per milliliter | GSK3008348 1000 mcg |
|---|---|
| Period 2: Cmax After Single Dose Administration of GSK3008348 | 10418.2 ± 31 |
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.
| Hours | GSK3008348 1000 mcg |
|---|---|
| Period 1: Time of Occurrence of Cmax (Tmax) After Single Dose Administration of GSK3008348 | 0.50 (0.4 to 0.5) |
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.
| Hours | GSK3008348 1000 mcg |
|---|---|
| Period 2: Tmax After Single Dose Administration of GSK3008348 | 0.47 (0.4 to 0.5) |
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.
| Hours | GSK3008348 1000 mcg |
|---|---|
| Period 1: Terminal Phase Half-life (t1/2) After Single Dose Administration of GSK3008348 | 10.6 ± 21 |
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.
No measurements were reported for this outcome.
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
| mL/cm^3 | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| Baseline, n=2,5 | 1.664 ± 19.67 | 1.503 ± 37.32 |
| 24 hours post-dose PET scan 2, n=1,3 | 1.530 ± NA | 1.474 ± 24.43 |
Collected over AEs and SAEs were collected from Day 1 up to 62 days. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) |
| GSK3008348 1000 mcg | 0/5 (0%) | 0/5 (0%) | 3/5 (60%) |
| Event | Placebo | GSK3008348 1000 mcg |
|---|---|---|
| DiarrhoeaGastrointestinal disorders | 1/3 | 0/5 |
| Urinary tract infectionInfections and infestations | 0/3 | 1/5 |
| HeadacheNervous system disorders | 0/3 | 1/5 |
| Dermatitis contactSkin and subcutaneous tissue disorders | 0/3 | 1/5 |
| Tooth extractionSurgical and medical procedures | 0/3 | 1/5 |
| Age, Continuous(Years) | Placebo | GSK3008348 1000 mcg | Total |
|---|---|---|---|
| Mean | 70.3 ± 3.06 | 73.6 ± 2.30 | 72.4 ± 2.92 |
| Sex: Female, Male(Participants) | Placebo | GSK3008348 1000 mcg | Total |
|---|---|---|---|
| Female | 0 | 1 | 1 |
| Male | 3 | 4 | 7 |
| Race/Ethnicity, Customized(Participants) | Placebo | GSK3008348 1000 mcg | Total |
|---|---|---|---|
| White | 3 | 5 | 8 |
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GlaxoSmithKline