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

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ClinicalTrials.gov Identifier: NCT03069989
Recruitment Status : Terminated (Sufficient information was gathered from cohort 1 to terminate the study without proceeding to optional cohort 2.)
First Posted : March 3, 2017
Results First Posted : August 12, 2019
Last Update Posted : August 12, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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.

Condition or disease Intervention/treatment Phase
Idiopathic Pulmonary Fibrosis Drug: GSK3008348 Drug: Placebo Drug: [18F]-FBA-A20FMDV2 Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : June 13, 2017
Actual Primary Completion Date : July 4, 2018
Actual Study Completion Date : July 18, 2018


Arm Intervention/treatment
Experimental: Cohort 1 GSK3008348
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
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.

Drug: [18F]-FBA-A20FMDV2
Radio-labeled peptide ligand for PET scan. Available as intravenous (IV) infusion, 20 mL.

Placebo Comparator: Cohort 1 Placebo
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
Solution for nebulisation. Available as clear colorless to pale yellow colored solution in a 5mL vial with 20mm stopper and aluminium seal.

Drug: [18F]-FBA-A20FMDV2
Radio-labeled peptide ligand for PET scan. Available as intravenous (IV) infusion, 20 mL.

Experimental: Cohort 2 GSK3008348
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
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.

Drug: [18F]-FBA-A20FMDV2
Radio-labeled peptide ligand for PET scan. Available as intravenous (IV) infusion, 20 mL.

Placebo Comparator: Cohort 2 Placebo
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
Solution for nebulisation. Available as clear colorless to pale yellow colored solution in a 5mL vial with 20mm stopper and aluminium seal.

Drug: [18F]-FBA-A20FMDV2
Radio-labeled peptide ligand for PET scan. Available as intravenous (IV) infusion, 20 mL.




Primary Outcome Measures :
  1. 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 [ Time Frame: Baseline (pre-dose) and 30 minutes post-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.

  2. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 62 days ]
    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.

  3. Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  4. Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  5. Period 1: Change From Baseline in Hematology Parameter: Hemoglobin [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  6. Period 2: Change From Baseline in Hematology Parameter: Hemoglobin [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  7. Period 1: Change From Baseline in Hematology Parameter: Hematocrit [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  8. Period 2: Change From Baseline in Hematology Parameter: Hematocrit [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  9. Period 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  10. Period 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  11. Period 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  12. Period 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  13. Period 1: Change From Baseline in Hematology Parameter: Red Blood Cell Count [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  14. Period 2: Change From Baseline in Hematology Parameter: Red Blood Cell Count [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  15. Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  16. Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  17. Period 1: Change From Baseline in Chemistry Parameters: Albumin and Total Protein [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  18. Period 2: Change From Baseline in Chemistry Parameters: Albumin and Total Protein [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  19. Period 1: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  20. Period 2: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  21. Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  22. Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  23. Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick [ Time Frame: Baseline (Day -1) and 24 hours post-GSK3008348 dose ]
    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.

  24. Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick [ Time Frame: Baseline (Day -1), 24 hours post-GSK3008348 dose and Day 15 (follow-up) ]
    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.

  25. Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) [ Time Frame: Baseline (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose ]
    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.

  26. Period 2: Change From Baseline in Vital Signs: DBP and SBP [ Time Frame: Baseline (Day -1), 30 minutes (post-PET scan), Day 1 (prior to discharge) and Day 2 (pre-PET scan) ]
    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.

  27. Period 1: Change From Baseline in Vital Signs: Heart Rate [ Time Frame: Baseline (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose ]
    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.

  28. Period 2: Change From Baseline in Vital Signs: Heart Rate [ Time Frame: Baseline (Day -1), 30 minutes (post-PET scan), Day 1 (prior to discharge) and Day 2 (pre-PET scan) ]
    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.

  29. Period 1: Change From Baseline in Vital Sign: Respiration Rate [ Time Frame: Baseline (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose ]
    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.

  30. Period 2: Change From Baseline in Vital Sign: Respiration Rate [ Time Frame: Baseline (Day -1), 30 minutes (post-PET scan), Day 1 (prior to discharge) and Day 2 (pre-PET scan) ]
    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.

  31. Period 1: Change From Baseline in Vital Sign: Temperature [ Time Frame: Baseline (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose ]
    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.

  32. Period 2: Change From Baseline in Vital Sign: Temperature [ Time Frame: Baseline (Day -1), 30 minutes (post-PET scan), Day 1 (prior to discharge) and Day 2 (pre-PET scan) ]
    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.

  33. Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters [ Time Frame: Pre-dose (Day -1), 0.5, 2, 4, 8 and 24 hours post-GSK3008348 dose ]
    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.

  34. Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters [ 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) ]
    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.

  35. Period 1: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) [ Time Frame: Baseline (Day -1), 1 hour and 24 hours post-GSK3008348 dose ]
    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 :
  1. Period 1: Area Under the Plasma Concentration-time Curve From Zero Hours to Time (AUC[0-t]) After Single Dose Administration of GSK3008348 [ Time Frame: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose ]
    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.

  2. Period 2: AUC(0-t) After Single Dose Administration of GSK3008348 [ Time Frame: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose ]
    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.

  3. Period 1: Area Under the Plasma Concentration-time Curve From Zero Hours to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3008348 [ Time Frame: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose ]
    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.

  4. Period 2: AUC(0-infinity) After Single Dose Administration of GSK3008348 [ Time Frame: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose ]
    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.

  5. Period 1: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3008348 [ Time Frame: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose ]
    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.

  6. Period 2: Cmax After Single Dose Administration of GSK3008348 [ Time Frame: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose ]
    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.

  7. Period 1: Time of Occurrence of Cmax (Tmax) After Single Dose Administration of GSK3008348 [ Time Frame: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose ]
    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.

  8. Period 2: Tmax After Single Dose Administration of GSK3008348 [ Time Frame: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose ]
    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.

  9. Period 1: Terminal Phase Half-life (t1/2) After Single Dose Administration of GSK3008348 [ Time Frame: Pre-dose, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18 and 24 hours post-GSK3008348 dose ]
    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.

  10. Period 2: t1/2 After Single Dose Administration of GSK3008348 [ Time Frame: Pre-dose, and at 0.25, 0.5, 2, 4, 22 and 30 hours post-GSK3008348 dose ]
    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.

  11. Period 2: VT of [18F]-FBAA20FMDV2 in the Whole Lung (Not Corrected for Air Volume) Approximately 24 Hours Post-dose Compared to Pre-dose [ Time Frame: Baseline (pre-dose) and 24 hours post-dose PET scan 2 ]
    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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03069989


Locations
Layout table for location information
United Kingdom
GSK Investigational Site
London, United Kingdom, SW3 6HP
GSK Investigational Site
London, United Kingdom, WC1E 6JF
GSK Investigational Site
London, United Kingdom
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Layout table for investigator information
Study Director: GSK Clinical Trials GlaxoSmithKline
  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:
Study Protocol  [PDF] January 24, 2018
Statistical Analysis Plan  [PDF] January 28, 2019


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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03069989     History of Changes
Other Study ID Numbers: 204715
2016-003674-41 ( EudraCT Number )
First Posted: March 3, 2017    Key Record Dates
Results First Posted: August 12, 2019
Last Update Posted: August 12, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Tolerability
IPF
PET imaging
Idiopathic Pulmonary Fibrosis
Safety
Pharmacokinetics
Double-blind
Additional relevant MeSH terms:
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Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Idiopathic Interstitial Pneumonias
Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Lung Diseases, Interstitial