Back to resultsSingle Doses of GSK3008348 in Idiopathic Pulmonary Fibrosis (IPF) Participants Using Positron Emission Tomography (PET) Imaging
Primary Purpose
Idiopathic Pulmonary Fibrosis
Status
Terminated
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
GSK3008348
Placebo
[18F]-FBA-A20FMDV2
Sponsored by
About this trial
This is an interventional treatment trial for Idiopathic Pulmonary Fibrosis focused on measuring Tolerability, IPF, PET imaging, Idiopathic Pulmonary Fibrosis, Safety, Pharmacokinetics, Double-blind
Eligibility Criteria
Inclusion Criteria:
- Male participants aged >= 50 years, and female participants aged >=55 years, at the time of signing the informed consent.
- Diagnosis of definite or probable IPF as determined by a responsible and experienced chest physician and based on established criteria defined by the American Thoracic Society/European Respiratory Society Internationale Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias.
- Ambulant and capable of attending outpatient visits.
- FVC > 50 percent predicted and DLCO > 40 percent predicted.
- Body weight >= 45 kilograms (kg) and body mass index (BMI) within the range 18.0-35.0 kg/square meter (inclusive).
- Male and female
- Male participants: A male participant must agree to use contraception as detailed in this protocol during the study and for at least 90 days after the follow up visit, and refrain from donating sperm during this period.
- Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP) as defined in the protocol.
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions, listed in the informed consent form (ICF) and in this protocol.
Exclusion Criteria:
- ALT and bilirubin > 1.5x upper limit of normal (ULN; isolated bilirubin > 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin < 35 percent).
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- QT corrected (QTc) > 450 milliseconds (msec), or QTc > 480 msec in participants with Bundle Branch Block.
- Current IPF exacerbation, or upper or lower respiratory tract infection on admission to the clinical unit.
- History of or suffers from claustrophobia, or unable to lie flat and still on their back for up to 2 hrs in the PET scanner.
- Extent of emphysema greater than the extent of fibrotic change on High-Resolution Computed Tomography (HRCT) scan, based on investigator judgment.
- FEV1/FVC ratio < 0.70 at screening (post-bronchodilator).
- History of sensitivity to the study treatment, or components thereof, or a history of drug or other allergy that, in the opinion of the investigators or Medical Monitor, contraindicates their participation.
- Any current oro-pharygneal disease or disorders as judged by the investigator.
- Currently taking pirfenidone or nintedanib, or received pirfenidone or nintedanib within 30 days of the first dose of study treatment.
- Taken, within 7 days or 5 half-lives (whichever is longer) before the first dose of study treatment, organic anion transporter (OAT) substrates with a narrow therapeutic index (example: methotrexate and tenofovir), vitamins, or dietary or herbal supplements, unless in the opinion of the investigator and sponsor the supplement will not interfere with the study medication.
- Long-term continuous home oxygen therapy (use of oxygen that is only intermittent and for symptom relief is acceptable).
- Participation in a clinical trial and receipt of an investigational medicinal product within the following time period before the first dose in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than 4 new investigational medicinal products within 12 months before the first dose.
- Presence of Hepatitis B surface antigen (HBsAg) at screening, or positive Hepatitis C antibody test result at screening or within 3 months before the first dose of study treatment.
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.
- Previous or current exposure to animals that may harbour Food and Mouth Disease Virus (FMDV2).
- Previous long term (>= 3 months) residence in a country where FMDV2 is endemic (such as certain areas of Africa, Asia and South America.
- Where participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 56 days.
- History of drug or alcohol abuse that in the opinion of the investigator affects their participation in the study.
- Exposure to ionizing radiation in excess of 10 Millisievert (mSv) above background over the previous 3 year period as a result of occupational exposure or previous participation in research studies. Clinically justified (therapeutic or diagnostic) exposures are not included in the exposure calculation.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
Cohort 1 GSK3008348
Cohort 1 Placebo
Cohort 2 GSK3008348
Cohort 2 Placebo
Arm Description
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03069989
Brief Title
Single Doses of GSK3008348 in Idiopathic Pulmonary Fibrosis (IPF) Participants Using Positron Emission Tomography (PET) Imaging
Official Title
A Study of Single Doses to Evaluate the Safety, Tolerability, Pharmacokinetics and Target Engagement of Nebulised GSK3008348 in Idiopathic Pulmonary Fibrosis Patients, Using Positron Emission Tomography (PET) Imaging
Study Type
Interventional
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Terminated
Why Stopped
Sufficient information was gathered from cohort 1 to terminate the study without proceeding to optional cohort 2.
Study Start Date
June 13, 2017 (Actual)
Primary Completion Date
July 4, 2018 (Actual)
Study Completion Date
July 18, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Pulmonary Fibrosis
Keywords
Tolerability, IPF, PET imaging, Idiopathic Pulmonary Fibrosis, Safety, Pharmacokinetics, Double-blind
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1 GSK3008348
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 1 Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Cohort 2 GSK3008348
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 2 Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
GSK3008348
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Solution for nebulisation. Available as clear colorless to pale yellow colored solution in a 5mL vial with 20mm stopper and aluminium seal.
Intervention Type
Drug
Intervention Name(s)
[18F]-FBA-A20FMDV2
Intervention Description
Radio-labeled peptide ligand for PET scan. Available as intravenous (IV) infusion, 20 mL.
Primary Outcome Measure Information:
Title
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
Description
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
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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
Title
Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count
Description
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
Title
Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count
Description
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
Title
Period 1: Change From Baseline in Hematology Parameter: Hemoglobin
Description
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
Title
Period 2: Change From Baseline in Hematology Parameter: Hemoglobin
Description
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
Title
Period 1: Change From Baseline in Hematology Parameter: Hematocrit
Description
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
Title
Period 2: Change From Baseline in Hematology Parameter: Hematocrit
Description
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
Title
Period 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin
Description
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
Title
Period 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin
Description
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
Title
Period 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume
Description
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
Title
Period 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume
Description
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
Title
Period 1: Change From Baseline in Hematology Parameter: Red Blood Cell Count
Description
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
Title
Period 2: Change From Baseline in Hematology Parameter: Red Blood Cell Count
Description
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
Title
Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase
Description
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
Title
Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase
Description
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
Title
Period 1: Change From Baseline in Chemistry Parameters: Albumin and Total Protein
Description
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
Title
Period 2: Change From Baseline in Chemistry Parameters: Albumin and Total Protein
Description
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
Title
Period 1: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine
Description
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
Title
Period 2: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine
Description
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
Title
Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen
Description
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
Title
Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen
Description
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
Title
Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick
Description
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
Title
Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick
Description
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)
Title
Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Description
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
Title
Period 2: Change From Baseline in Vital Signs: DBP and SBP
Description
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)
Title
Period 1: Change From Baseline in Vital Signs: Heart Rate
Description
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
Title
Period 2: Change From Baseline in Vital Signs: Heart Rate
Description
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)
Title
Period 1: Change From Baseline in Vital Sign: Respiration Rate
Description
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
Title
Period 2: Change From Baseline in Vital Sign: Respiration Rate
Description
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)
Title
Period 1: Change From Baseline in Vital Sign: Temperature
Description
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
Title
Period 2: Change From Baseline in Vital Sign: Temperature
Description
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)
Title
Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters
Description
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
Title
Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters
Description
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)
Title
Period 1: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC)
Description
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
Secondary Outcome Measure Information:
Title
Period 1: Area Under the Plasma Concentration-time Curve From Zero Hours to Time (AUC[0-t]) After Single Dose Administration of GSK3008348
Description
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
Title
Period 2: AUC(0-t) After Single Dose Administration of GSK3008348
Description
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
Title
Period 1: Area Under the Plasma Concentration-time Curve From Zero Hours to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3008348
Description
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
Title
Period 2: AUC(0-infinity) After Single Dose Administration of GSK3008348
Description
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
Title
Period 1: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3008348
Description
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
Title
Period 2: Cmax After Single Dose Administration of GSK3008348
Description
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
Title
Period 1: Time of Occurrence of Cmax (Tmax) After Single Dose Administration of GSK3008348
Description
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
Title
Period 2: Tmax After Single Dose Administration of GSK3008348
Description
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
Title
Period 1: Terminal Phase Half-life (t1/2) After Single Dose Administration of GSK3008348
Description
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
Title
Period 2: t1/2 After Single Dose Administration of GSK3008348
Description
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
Title
Period 2: VT of [18F]-FBAA20FMDV2 in the Whole Lung (Not Corrected for Air Volume) Approximately 24 Hours Post-dose Compared to Pre-dose
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male participants aged >= 50 years, and female participants aged >=55 years, at the time of signing the informed consent.
Diagnosis of definite or probable IPF as determined by a responsible and experienced chest physician and based on established criteria defined by the American Thoracic Society/European Respiratory Society Internationale Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias.
Ambulant and capable of attending outpatient visits.
FVC > 50 percent predicted and DLCO > 40 percent predicted.
Body weight >= 45 kilograms (kg) and body mass index (BMI) within the range 18.0-35.0 kg/square meter (inclusive).
Male and female
Male participants: A male participant must agree to use contraception as detailed in this protocol during the study and for at least 90 days after the follow up visit, and refrain from donating sperm during this period.
Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP) as defined in the protocol.
Capable of giving signed informed consent, which includes compliance with the requirements and restrictions, listed in the informed consent form (ICF) and in this protocol.
Exclusion Criteria:
ALT and bilirubin > 1.5x upper limit of normal (ULN; isolated bilirubin > 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin < 35 percent).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
QT corrected (QTc) > 450 milliseconds (msec), or QTc > 480 msec in participants with Bundle Branch Block.
Current IPF exacerbation, or upper or lower respiratory tract infection on admission to the clinical unit.
History of or suffers from claustrophobia, or unable to lie flat and still on their back for up to 2 hrs in the PET scanner.
Extent of emphysema greater than the extent of fibrotic change on High-Resolution Computed Tomography (HRCT) scan, based on investigator judgment.
FEV1/FVC ratio < 0.70 at screening (post-bronchodilator).
History of sensitivity to the study treatment, or components thereof, or a history of drug or other allergy that, in the opinion of the investigators or Medical Monitor, contraindicates their participation.
Any current oro-pharygneal disease or disorders as judged by the investigator.
Currently taking pirfenidone or nintedanib, or received pirfenidone or nintedanib within 30 days of the first dose of study treatment.
Taken, within 7 days or 5 half-lives (whichever is longer) before the first dose of study treatment, organic anion transporter (OAT) substrates with a narrow therapeutic index (example: methotrexate and tenofovir), vitamins, or dietary or herbal supplements, unless in the opinion of the investigator and sponsor the supplement will not interfere with the study medication.
Long-term continuous home oxygen therapy (use of oxygen that is only intermittent and for symptom relief is acceptable).
Participation in a clinical trial and receipt of an investigational medicinal product within the following time period before the first dose in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Exposure to more than 4 new investigational medicinal products within 12 months before the first dose.
Presence of Hepatitis B surface antigen (HBsAg) at screening, or positive Hepatitis C antibody test result at screening or within 3 months before the first dose of study treatment.
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.
Previous or current exposure to animals that may harbour Food and Mouth Disease Virus (FMDV2).
Previous long term (>= 3 months) residence in a country where FMDV2 is endemic (such as certain areas of Africa, Asia and South America.
Where participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 56 days.
History of drug or alcohol abuse that in the opinion of the investigator affects their participation in the study.
Exposure to ionizing radiation in excess of 10 Millisievert (mSv) above background over the previous 3 year period as a result of occupational exposure or previous participation in research studies. Clinically justified (therapeutic or diagnostic) exposures are not included in the exposure calculation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
London
ZIP/Postal Code
SW3 6HP
Country
United Kingdom
Facility Name
GSK Investigational Site
City
London
ZIP/Postal Code
WC1E 6JF
Country
United Kingdom
Facility Name
GSK Investigational Site
City
London
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Single Doses of GSK3008348 in Idiopathic Pulmonary Fibrosis (IPF) Participants Using Positron Emission Tomography (PET) Imaging
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