Idiopathic Pulmonary Fibrosis
Conditions
Keywords
Tolerability, IPF, PET imaging, Idiopathic Pulmonary Fibrosis, Safety, Pharmacokinetics, Double-blind
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.
Interventions
DRUGGSK3008348
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.
DRUGPlacebo
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.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Period 1: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | 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. |
| Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick | 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. |
| Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | 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. |
| Period 2: Change From Baseline in Vital Signs: DBP and SBP | 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. |
| Period 1: Change From Baseline in Vital Signs: Heart Rate | 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. |
| Period 2: Change From Baseline in Vital Signs: Heart Rate | 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. |
| Period 1: Change From Baseline in Vital Sign: Respiration Rate | 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. |
| Period 2: Change From Baseline in Vital Sign: Respiration Rate | 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. |
| Period 1: Change From Baseline in Vital Sign: Temperature | 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. |
| Period 2: Change From Baseline in Vital Sign: Temperature | 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. |
| Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 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. |
| Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | 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. |
| Period 2: Volume of Distribution (VT) of [18F]-FBA-A20FMDV2 in the Whole Lung (Not Corrected for Air Volume) at 30 Minutes Post-dose Compared to Pre-dose | Baseline (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. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. |
| Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count | 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. |
| Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count | 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. |
| Period 1: Change From Baseline in Hematology Parameter: Hemoglobin | 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. |
| Period 2: Change From Baseline in Hematology Parameter: Hemoglobin | 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. |
| Period 1: Change From Baseline in Hematology Parameter: Hematocrit | 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. |
| Period 2: Change From Baseline in Hematology Parameter: Hematocrit | 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. |
| Period 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin | 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. |
| Period 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin | 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. |
| Period 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume | 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. |
| Period 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume | 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. |
| Period 1: Change From Baseline in Hematology Parameter: Red Blood Cell Count | 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. |
| Period 2: Change From Baseline in Hematology Parameter: Red Blood Cell Count | 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. |
| Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | 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. |
| Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | 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. |
| Period 1: Change From Baseline in Chemistry Parameters: Albumin and Total Protein | 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. |
| Period 2: Change From Baseline in Chemistry Parameters: Albumin and Total Protein | 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. |
| Period 1: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | 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. |
| Period 2: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | 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. |
| Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | 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. |
| Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | 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. |
| Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Period 2: AUC(0-t) After Single Dose Administration of GSK3008348 | 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. |
| Period 1: Area Under the Plasma Concentration-time Curve From Zero Hours to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3008348 | 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. |
| Period 2: AUC(0-infinity) After Single Dose Administration of GSK3008348 | 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. |
| Period 1: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3008348 | 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. |
| Period 2: Cmax After Single Dose Administration of GSK3008348 | 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. |
| Period 1: Time of Occurrence of Cmax (Tmax) After Single Dose Administration of GSK3008348 | 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. |
| Period 2: Tmax After Single Dose Administration of GSK3008348 | 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. |
| Period 1: Terminal Phase Half-life (t1/2) After Single Dose Administration of GSK3008348 | 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. |
| Period 2: t1/2 After Single Dose Administration of GSK3008348 | 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. |
| Period 2: VT of [18F]-FBAA20FMDV2 in the Whole Lung (Not Corrected for Air Volume) Approximately 24 Hours Post-dose Compared to Pre-dose | Baseline (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 |
| Period 1: Area Under the Plasma Concentration-time Curve From Zero Hours to Time (AUC[0-t]) After Single Dose Administration of GSK3008348 | 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. |
Countries
United Kingdom
Participant flow
Recruitment details
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.
Pre-assignment details
A total of 11 participants were screened, of which 3 were screening failures. Two screening failure participants did not meet inclusion/exclusion criteria and 1 participant withdrew consent. Hence, 8 participants were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a single dose of placebo (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of a \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV2 administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2. | 3 |
| GSK3008348 1000 mcg Participants received a single dose of GSK3008348 1000 mcg (solution), inhaled via nebulization on Day 1 in dosing periods 1 and 2. In dosing period 2 only, they received up to 150 MBq of \[18F\]-FBA-A20FMDV2, via IV infusion, prior to PET imaging at Baseline, 30 minutes and approximately 24 hours post-GSK3008348 dose. Total \[18F\]-FBA-A20FMDV administration was \<=100 mcg per participant. A wash out period of at least 7 and no more than 28 days was maintained between doses in Periods 1 and 2. | 5 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Dosing Period 2 (Up to 16 Days) | Protocol-defined stop criteria reached | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | GSK3008348 1000 mcg | Total |
|---|---|---|---|
| Age, Continuous | 70.3 Years STANDARD_DEVIATION 3.06 | 73.6 Years STANDARD_DEVIATION 2.3 | 72.4 Years STANDARD_DEVIATION 2.92 |
| Race/Ethnicity, Customized White | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 5 |
| other Total, other adverse events | 1 / 3 | 3 / 5 |
| serious Total, serious adverse events | 0 / 3 | 0 / 5 |
Outcome results
Primary
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
Population: Intent-to-Treat Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 1 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| GSK3008348 1000 mcg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 3 Participants |
| GSK3008348 1000 mcg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
Primary
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
Population: Intent-to-Treat Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 1: Change From Baseline in Chemistry Parameters: Albumin and Total Protein | Albumin | -1.3 Grams per liter | Standard Deviation 1.15 |
| Placebo | Period 1: Change From Baseline in Chemistry Parameters: Albumin and Total Protein | Total protein | -1.7 Grams per liter | Standard Deviation 2.89 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Chemistry Parameters: Albumin and Total Protein | Albumin | -2.6 Grams per liter | Standard Deviation 3.78 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Chemistry Parameters: Albumin and Total Protein | Total protein | -4.0 Grams per liter | Standard Deviation 6.4 |
Primary
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
Population: Intent-to-Treat Population. Only those participants available at the indicated time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Alanine amino transferase, n=3,5 | 1.3 International units per liter | Standard Deviation 1.53 |
| Placebo | Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Creatine kinase, n=3,5 | -95.0 International units per liter | Standard Deviation 76.62 |
| Placebo | Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Aspartate amino transferase, n=2,3 | 0.0 International units per liter | Standard Deviation 2.83 |
| Placebo | Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Gamma glutamyl transferase, n=3,5 | -1.0 International units per liter | Standard Deviation 1 |
| Placebo | Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Alkaline phosphatase, n=3,5 | -1.7 International units per liter | Standard Deviation 1.53 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Gamma glutamyl transferase, n=3,5 | -1.2 International units per liter | Standard Deviation 2.17 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Alkaline phosphatase, n=3,5 | -3.4 International units per liter | Standard Deviation 10.43 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Alanine amino transferase, n=3,5 | -0.6 International units per liter | Standard Deviation 1.14 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Aspartate amino transferase, n=2,3 | -0.3 International units per liter | Standard Deviation 3.06 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Creatine kinase, n=3,5 | -13.8 International units per liter | Standard Deviation 9.31 |
Primary
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
Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Glucose, n=3,5 | 1.17 Millimoles per liter | Standard Deviation 1.858 |
| Placebo | Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Sodium, n=3,5 | -2.7 Millimoles per liter | Standard Deviation 1.15 |
| Placebo | Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Potassium, n=2,5 | -0.10 Millimoles per liter | Standard Deviation 0 |
| Placebo | Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Blood urea nitrogen, n=3,5 | -0.27 Millimoles per liter | Standard Deviation 1.234 |
| Placebo | Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Calcium, n=3,5 | -0.103 Millimoles per liter | Standard Deviation 0.0961 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Blood urea nitrogen, n=3,5 | 0.14 Millimoles per liter | Standard Deviation 1.174 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Calcium, n=3,5 | -0.024 Millimoles per liter | Standard Deviation 0.1097 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Glucose, n=3,5 | 1.06 Millimoles per liter | Standard Deviation 1.126 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Potassium, n=2,5 | -0.48 Millimoles per liter | Standard Deviation 0.311 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Sodium, n=3,5 | -0.2 Millimoles per liter | Standard Deviation 1.64 |
Primary
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
Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 1: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Direct bilirubin, n=2,4 | 0.0 Micromoles per liter | Standard Deviation 0 |
| Placebo | Period 1: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Total bilirubin, n=3,5 | -3.0 Micromoles per liter | Standard Deviation 1 |
| Placebo | Period 1: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Creatinine, n=3,5 | -6.0 Micromoles per liter | Standard Deviation 15.1 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Direct bilirubin, n=2,4 | -0.5 Micromoles per liter | Standard Deviation 1.73 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Total bilirubin, n=3,5 | -2.2 Micromoles per liter | Standard Deviation 6.46 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Creatinine, n=3,5 | -3.6 Micromoles per liter | Standard Deviation 5.59 |
Primary
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
Population: Intent-to-Treat Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 1: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1: 1 hour | 0.003 Liters | Standard Deviation 0.0808 |
| Placebo | Period 1: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1: 24 hours | -0.117 Liters | Standard Deviation 0.0702 |
| Placebo | Period 1: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC: 1 hour | 0.067 Liters | Standard Deviation 0.0833 |
| Placebo | Period 1: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC: 24 hours | -0.050 Liters | Standard Deviation 0.1411 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC: 24 hours | -0.010 Liters | Standard Deviation 0.1208 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1: 1 hour | -0.058 Liters | Standard Deviation 0.0881 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC: 1 hour | 0.086 Liters | Standard Deviation 0.3474 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1: 24 hours | -0.036 Liters | Standard Deviation 0.0879 |
Primary
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
Population: Intent-to-Treat Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Period 1: Change From Baseline in Hematology Parameter: Hematocrit | 0.000 Proportion of red blood cells in blood | Standard Deviation 0 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Hematology Parameter: Hematocrit | -0.016 Proportion of red blood cells in blood | Standard Deviation 0.027 |
Primary
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
Population: Intent-to-Treat Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Period 1: Change From Baseline in Hematology Parameter: Hemoglobin | -4.3 Grams per liter | Standard Deviation 2.89 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Hematology Parameter: Hemoglobin | -4.4 Grams per liter | Standard Deviation 6.84 |
Primary
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
Population: Intent-to-Treat Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Period 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin | -0.30 Picrograms | Standard Deviation 0.265 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin | 0.10 Picrograms | Standard Deviation 0.5 |
Primary
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
Population: Intent-to-Treat Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Period 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume | 1.00 Femtoliters | Standard Deviation 1 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume | -0.58 Femtoliters | Standard Deviation 1.559 |
Primary
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
Population: Intent-to-Treat Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Period 1: Change From Baseline in Hematology Parameter: Red Blood Cell Count | -0.093 Trillion cells per liter | Standard Deviation 0.0702 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Hematology Parameter: Red Blood Cell Count | -0.168 Trillion cells per liter | Standard Deviation 0.2946 |
Primary
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
Population: Intent-to-Treat Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count | WBC count | 0.467 Giga cells per liter | Standard Deviation 0.4933 |
| Placebo | Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count | Basophils | 0.000 Giga cells per liter | Standard Deviation 0 |
| Placebo | Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count | Eosinophils | 0.000 Giga cells per liter | Standard Deviation 0 |
| Placebo | Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count | Lymphocytes | 0.267 Giga cells per liter | Standard Deviation 0.0577 |
| Placebo | Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count | Monocytes | -0.033 Giga cells per liter | Standard Deviation 0.0577 |
| Placebo | Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count | Total neutrophils | 0.300 Giga cells per liter | Standard Deviation 0.5292 |
| Placebo | Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count | Platelet count | -3.0 Giga cells per liter | Standard Deviation 16.46 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count | WBC count | -0.982 Giga cells per liter | Standard Deviation 0.9509 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count | Monocytes | -0.106 Giga cells per liter | Standard Deviation 0.1232 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count | Basophils | -0.008 Giga cells per liter | Standard Deviation 0.0179 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count | Platelet count | -24.2 Giga cells per liter | Standard Deviation 11.69 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count | Eosinophils | 0.018 Giga cells per liter | Standard Deviation 0.0402 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count | Total neutrophils | -0.762 Giga cells per liter | Standard Deviation 0.8135 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count | Lymphocytes | -0.086 Giga cells per liter | Standard Deviation 0.3361 |
Primary
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
Population: Intent-to-Treat Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 1: Change From Baseline in Vital Sign: Respiration Rate | 2 hours | 1.0 Breaths per minute | Standard Deviation 1 |
| Placebo | Period 1: Change From Baseline in Vital Sign: Respiration Rate | 8 hours | 0.3 Breaths per minute | Standard Deviation 0.58 |
| Placebo | Period 1: Change From Baseline in Vital Sign: Respiration Rate | 4 hours | 1.0 Breaths per minute | Standard Deviation 1 |
| Placebo | Period 1: Change From Baseline in Vital Sign: Respiration Rate | 24 hours | -0.7 Breaths per minute | Standard Deviation 1.15 |
| Placebo | Period 1: Change From Baseline in Vital Sign: Respiration Rate | 0.5 hours | -0.3 Breaths per minute | Standard Deviation 1.53 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Sign: Respiration Rate | 24 hours | 1.0 Breaths per minute | Standard Deviation 2 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Sign: Respiration Rate | 0.5 hours | 1.2 Breaths per minute | Standard Deviation 2.17 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Sign: Respiration Rate | 2 hours | 2.8 Breaths per minute | Standard Deviation 3.7 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Sign: Respiration Rate | 4 hours | 1.6 Breaths per minute | Standard Deviation 2.19 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Sign: Respiration Rate | 8 hours | 2.2 Breaths per minute | Standard Deviation 3.56 |
Primary
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
Population: Intent-to-Treat Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP- 0.5 hours | 3.3 Millimeters of mercury | Standard Deviation 9.29 |
| Placebo | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP- 2 hours | 1.3 Millimeters of mercury | Standard Deviation 1.15 |
| Placebo | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP- 4 hours | -7.0 Millimeters of mercury | Standard Deviation 5.29 |
| Placebo | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP- 8 hours | -0.7 Millimeters of mercury | Standard Deviation 9.29 |
| Placebo | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP- 24 hours | -5.7 Millimeters of mercury | Standard Deviation 5.51 |
| Placebo | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP- 0.5 hours | 16.3 Millimeters of mercury | Standard Deviation 24.17 |
| Placebo | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP- 2 hours | 5.0 Millimeters of mercury | Standard Deviation 3.61 |
| Placebo | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP- 4 hours | -1.7 Millimeters of mercury | Standard Deviation 4.73 |
| Placebo | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP- 8 hours | 12.0 Millimeters of mercury | Standard Deviation 23.9 |
| Placebo | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP- 24 hours | 1.3 Millimeters of mercury | Standard Deviation 11.59 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP- 4 hours | -4.8 Millimeters of mercury | Standard Deviation 14.75 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP- 0.5 hours | 2.4 Millimeters of mercury | Standard Deviation 9.91 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP- 0.5 hours | 2.2 Millimeters of mercury | Standard Deviation 20.07 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP- 2 hours | -0.6 Millimeters of mercury | Standard Deviation 3.21 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP- 24 hours | -5.0 Millimeters of mercury | Standard Deviation 12.51 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP- 4 hours | 0.2 Millimeters of mercury | Standard Deviation 6.8 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP- 2 hours | -11.0 Millimeters of mercury | Standard Deviation 4.36 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP- 8 hours | 1.4 Millimeters of mercury | Standard Deviation 10.36 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP- 8 hours | 1.8 Millimeters of mercury | Standard Deviation 16.53 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP- 24 hours | -4.4 Millimeters of mercury | Standard Deviation 6.31 |
Primary
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
Population: Intent-to-Treat Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 1: Change From Baseline in Vital Signs: Heart Rate | 2 hours | 4.0 Beats per minute | Standard Deviation 4.58 |
| Placebo | Period 1: Change From Baseline in Vital Signs: Heart Rate | 8 hours | 17.3 Beats per minute | Standard Deviation 2.08 |
| Placebo | Period 1: Change From Baseline in Vital Signs: Heart Rate | 4 hours | 12.3 Beats per minute | Standard Deviation 9.81 |
| Placebo | Period 1: Change From Baseline in Vital Signs: Heart Rate | 24 hours | 6.7 Beats per minute | Standard Deviation 3.51 |
| Placebo | Period 1: Change From Baseline in Vital Signs: Heart Rate | 0.5 hours | -0.3 Beats per minute | Standard Deviation 9.29 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Signs: Heart Rate | 24 hours | 0.8 Beats per minute | Standard Deviation 5.93 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Signs: Heart Rate | 0.5 hours | -7.0 Beats per minute | Standard Deviation 11.11 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Signs: Heart Rate | 2 hours | -3.0 Beats per minute | Standard Deviation 10.49 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Signs: Heart Rate | 4 hours | -2.4 Beats per minute | Standard Deviation 6.23 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Signs: Heart Rate | 8 hours | -1.4 Beats per minute | Standard Deviation 10.11 |
Primary
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
Population: Intent-to-Treat Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 1: Change From Baseline in Vital Sign: Temperature | 2 hours | 0.30 Celsius | Standard Deviation 0.656 |
| Placebo | Period 1: Change From Baseline in Vital Sign: Temperature | 8 hours | 0.43 Celsius | Standard Deviation 0.289 |
| Placebo | Period 1: Change From Baseline in Vital Sign: Temperature | 4 hours | 0.20 Celsius | Standard Deviation 0.265 |
| Placebo | Period 1: Change From Baseline in Vital Sign: Temperature | 24 hours | 0.60 Celsius | Standard Deviation 0.361 |
| Placebo | Period 1: Change From Baseline in Vital Sign: Temperature | 0.5 hours | 0.27 Celsius | Standard Deviation 0.231 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Sign: Temperature | 24 hours | 0.10 Celsius | Standard Deviation 0.292 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Sign: Temperature | 0.5 hours | 0.0 Celsius | Standard Deviation 0.346 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Sign: Temperature | 2 hours | 0.00 Celsius | Standard Deviation 0.265 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Sign: Temperature | 4 hours | -0.02 Celsius | Standard Deviation 0.327 |
| GSK3008348 1000 mcg | Period 1: Change From Baseline in Vital Sign: Temperature | 8 hours | 0.28 Celsius | Standard Deviation 0.319 |
Primary
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
Population: Intent-to-Treat Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 2 hours measurement 3, CS | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 0.5 hours measurement 2, NCS | 3 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 4 hours measurement 1, NCS | 3 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | Pre-dose measurement 1, NCS | 2 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 4 hours measurement 1, CS | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 0.5 hours measurement 2, CS | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 4 hours measurement 2, NCS | 3 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | Pre-dose measurement 3, NCS | 3 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 4 hours measurement 3, NCS | 3 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 0.5 hours measurement 3, NCS | 3 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 4 hours measurement 3, CS | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 4 hours measurement 2, CS | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 8 hours measurement 1, NCS | 3 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 0.5 hours measurement 3, CS | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 8 hours measurement 1, CS | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | Pre-dose measurement 3, CS | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 8 hours measurement 2, NCS | 3 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 2 hours measurement 1, NCS | 3 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 8 hours measurement 2, CS | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | Pre-dose measurement 1, CS | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 8 hours measurement 3, NCS | 3 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 2 hours measurement 1, CS | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 8 hours measurement 3, CS | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 0.5 hours measurement 1, NCS | 2 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 24 hours measurement 1, NCS | 3 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 2 hours measurement 2, NCS | 3 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 24 hours measurement 1, CS | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | Pre-dose measurement 2, NCS | 2 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 24 hours measurement 2, NCS | 3 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 2 hours measurement 2, CS | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 24 hours measurement 2, CS | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 0.5 hours measurement 1, CS | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 24 hours measurement 3, NCS | 2 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 2 hours measurement 3, NCS | 3 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 24 hours measurement 3, CS | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | Pre-dose measurement 2, CS | 0 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 24 hours measurement 3, CS | 0 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 4 hours measurement 2, CS | 0 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | Pre-dose measurement 1, NCS | 4 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | Pre-dose measurement 2, NCS | 3 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | Pre-dose measurement 2, CS | 0 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | Pre-dose measurement 3, NCS | 3 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | Pre-dose measurement 3, CS | 0 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 0.5 hours measurement 1, NCS | 4 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 0.5 hours measurement 1, CS | 0 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 0.5 hours measurement 2, NCS | 4 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 0.5 hours measurement 2, CS | 0 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 0.5 hours measurement 3, NCS | 4 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 0.5 hours measurement 3, CS | 0 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 2 hours measurement 1, NCS | 3 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 2 hours measurement 1, CS | 0 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 2 hours measurement 2, NCS | 3 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 2 hours measurement 2, CS | 0 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 2 hours measurement 3, NCS | 3 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 2 hours measurement 3, CS | 0 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 4 hours measurement 1, NCS | 4 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 4 hours measurement 1, CS | 0 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 4 hours measurement 2, NCS | 4 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 4 hours measurement 3, NCS | 4 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 4 hours measurement 3, CS | 0 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 8 hours measurement 1, NCS | 4 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 8 hours measurement 1, CS | 0 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 8 hours measurement 2, NCS | 4 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 8 hours measurement 2, CS | 0 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 8 hours measurement 3, NCS | 4 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 8 hours measurement 3, CS | 0 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 24 hours measurement 1, NCS | 4 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 24 hours measurement 1, CS | 0 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 24 hours measurement 2, NCS | 4 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 24 hours measurement 2, CS | 0 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | 24 hours measurement 3, NCS | 4 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Findings for 12-lead Electrocardiograms (ECG) Parameters | Pre-dose measurement 1, CS | 0 Participants |
Primary
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
Population: Intent-to-Treat Population. Only those participants with available at the indicated time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine occult blood- 24 hours, Trace: n=3,4 | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine protein- Baseline, 1+: n=3,4 | 1 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine occult blood- 24 hours, 1+: n=3,4 | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine protein - 24 hours, 1+: n=3,4 | 0 Participants |
| Placebo | Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine occult blood- Baseline, 1+: n=3,5 | 0 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine protein - 24 hours, 1+: n=3,4 | 1 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine occult blood- Baseline, 1+: n=3,5 | 1 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine occult blood- 24 hours, Trace: n=3,4 | 1 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine occult blood- 24 hours, 1+: n=3,4 | 1 Participants |
| GSK3008348 1000 mcg | Period 1: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine protein- Baseline, 1+: n=3,4 | 0 Participants |
Primary
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
Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 2: Change From Baseline in Chemistry Parameters: Albumin and Total Protein | Albumin | 1.5 Grams per liter | Standard Deviation 0.71 |
| Placebo | Period 2: Change From Baseline in Chemistry Parameters: Albumin and Total Protein | Total protein | -0.5 Grams per liter | Standard Deviation 0.71 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Chemistry Parameters: Albumin and Total Protein | Albumin | -1.4 Grams per liter | Standard Deviation 1.52 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Chemistry Parameters: Albumin and Total Protein | Total protein | -7.4 Grams per liter | Standard Deviation 5.55 |
Primary
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
Population: Intent-to-Treat Population. Only those participants available at the indicated time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Alanine amino transferase, n=2,4 | 4.0 International units per liter | Standard Deviation 1.41 |
| Placebo | Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Creatine kinase, n=2,4 | -94.0 International units per liter | Standard Deviation 127.28 |
| Placebo | Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Aspartate amino transferase, n=2,2 | 2.5 International units per liter | Standard Deviation 2.12 |
| Placebo | Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Gamma glutamyl transferase, n=2,3 | -5.0 International units per liter | Standard Deviation 1.41 |
| Placebo | Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Alkaline phosphatase, n=2,4 | -4.5 International units per liter | Standard Deviation 0.71 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Gamma glutamyl transferase, n=2,3 | -4.0 International units per liter | Standard Deviation 2.65 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Alkaline phosphatase, n=2,4 | -14.5 International units per liter | Standard Deviation 17.41 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Alanine amino transferase, n=2,4 | -0.5 International units per liter | Standard Deviation 3.7 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Aspartate amino transferase, n=2,2 | -6.5 International units per liter | Standard Deviation 6.36 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase | Creatine kinase, n=2,4 | -7.8 International units per liter | Standard Deviation 20.45 |
Primary
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
Population: Intent-to-Treat Population. Only those participants available at the indicated time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Glucose, n=2,5 | -0.25 Millimoles per liter | Standard Deviation 0.778 |
| Placebo | Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Sodium, n=2,5 | 0.5 Millimoles per liter | Standard Deviation 2.12 |
| Placebo | Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Potassium, n=2,4 | 0.00 Millimoles per liter | Standard Deviation 0.141 |
| Placebo | Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Blood urea nitrogen, n=2,5 | -0.25 Millimoles per liter | Standard Deviation 0.354 |
| Placebo | Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Calcium, n=2,5 | -0.125 Millimoles per liter | Standard Deviation 0.0778 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Blood urea nitrogen, n=2,5 | -0.06 Millimoles per liter | Standard Deviation 0.95 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Calcium, n=2,5 | -0.158 Millimoles per liter | Standard Deviation 0.1033 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Glucose, n=2,5 | -1.06 Millimoles per liter | Standard Deviation 1.403 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Potassium, n=2,4 | -0.20 Millimoles per liter | Standard Deviation 0.583 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen | Sodium, n=2,5 | 0.4 Millimoles per liter | Standard Deviation 3.36 |
Primary
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
Population: Intent-to-Treat Population. Only those participants with available at the indicated time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 2: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Direct bilirubin, n=1,3 | 2.0 Micromoles per liter | — |
| Placebo | Period 2: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Total bilirubin, n=2,5 | -2.5 Micromoles per liter | Standard Deviation 0.71 |
| Placebo | Period 2: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Creatinine, n=2,5 | -5.0 Micromoles per liter | Standard Deviation 16.97 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Creatinine, n=2,5 | -2.0 Micromoles per liter | Standard Deviation 5.61 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Direct bilirubin, n=1,3 | 1.3 Micromoles per liter | Standard Deviation 1.53 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine | Total bilirubin, n=2,5 | -4.8 Micromoles per liter | Standard Deviation 4.02 |
Primary
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
Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Period 2: Change From Baseline in Hematology Parameter: Hematocrit | -0.013 Proportion of red blood cells in blood | Standard Deviation 0.0057 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Hematology Parameter: Hematocrit | -0.028 Proportion of red blood cells in blood | Standard Deviation 0.0141 |
Primary
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
Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Period 2: Change From Baseline in Hematology Parameter: Hemoglobin | -4.0 Grams per liter | Standard Deviation 5.66 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Hematology Parameter: Hemoglobin | -8.8 Grams per liter | Standard Deviation 3.56 |
Primary
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
Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Period 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin | -0.75 Picrograms | Standard Deviation 0.212 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin | -0.50 Picrograms | Standard Deviation 0.361 |
Primary
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
Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Period 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume | -2.35 Femtoliters | Standard Deviation 1.061 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume | -1.62 Femtoliters | Standard Deviation 1.213 |
Primary
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
Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Period 2: Change From Baseline in Hematology Parameter: Red Blood Cell Count | -0.010 Trillion cells per liter | Standard Deviation 0.1556 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Hematology Parameter: Red Blood Cell Count | -0.226 Trillion cells per liter | Standard Deviation 0.1372 |
Primary
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
Population: Intent-to-Treat Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count | Lymphocytes | 0.485 Giga cells per liter | Standard Deviation 0.1061 |
| Placebo | Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count | Total neutrophils | -0.155 Giga cells per liter | Standard Deviation 0.5728 |
| Placebo | Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count | Eosinophils | 0.025 Giga cells per liter | Standard Deviation 0.0071 |
| Placebo | Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count | Platelet count | -2.5 Giga cells per liter | Standard Deviation 16.26 |
| Placebo | Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count | Monocytes | -0.050 Giga cells per liter | Standard Deviation 0.1414 |
| Placebo | Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count | WBC count | 0.270 Giga cells per liter | Standard Deviation 0.5657 |
| Placebo | Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count | Basophils | 0.010 Giga cells per liter | Standard Deviation 0.0424 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count | WBC count | -0.748 Giga cells per liter | Standard Deviation 0.7351 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count | Basophils | -0.034 Giga cells per liter | Standard Deviation 0.0365 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count | Eosinophils | -0.030 Giga cells per liter | Standard Deviation 0.1051 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count | Lymphocytes | 0.168 Giga cells per liter | Standard Deviation 0.3269 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count | Monocytes | -0.046 Giga cells per liter | Standard Deviation 0.1172 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count | Total neutrophils | -0.866 Giga cells per liter | Standard Deviation 0.6179 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and WBC Count | Platelet count | 15.8 Giga cells per liter | Standard Deviation 12.87 |
Primary
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)
Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 2: Change From Baseline in Vital Sign: Respiration Rate | 30 minutes post-PET scan | 0.0 Breaths per minute | Standard Deviation 2.83 |
| Placebo | Period 2: Change From Baseline in Vital Sign: Respiration Rate | Day 1 prior to discharge | 0.0 Breaths per minute | Standard Deviation 2.83 |
| Placebo | Period 2: Change From Baseline in Vital Sign: Respiration Rate | Day 2 pre-PET scan | -0.5 Breaths per minute | Standard Deviation 0.71 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Vital Sign: Respiration Rate | 30 minutes post-PET scan | 0.0 Breaths per minute | Standard Deviation 0 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Vital Sign: Respiration Rate | Day 1 prior to discharge | 2.8 Breaths per minute | Standard Deviation 1.1 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Vital Sign: Respiration Rate | Day 2 pre-PET scan | 1.0 Breaths per minute | Standard Deviation 2.24 |
Primary
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)
Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 2: Change From Baseline in Vital Signs: DBP and SBP | DBP-30 minutes post-PET scan | 17.0 Millimeter of mercury | Standard Deviation 12.73 |
| Placebo | Period 2: Change From Baseline in Vital Signs: DBP and SBP | DBP- Day 1 prior to discharge | 10.0 Millimeter of mercury | Standard Deviation 14.14 |
| Placebo | Period 2: Change From Baseline in Vital Signs: DBP and SBP | DBP- Day 2 pre-PET scan | 7.5 Millimeter of mercury | Standard Deviation 20.51 |
| Placebo | Period 2: Change From Baseline in Vital Signs: DBP and SBP | SBP- 30 minutes post-PET scan | 13.5 Millimeter of mercury | Standard Deviation 20.51 |
| Placebo | Period 2: Change From Baseline in Vital Signs: DBP and SBP | SBP- Day 1 prior to discharge | 10.0 Millimeter of mercury | Standard Deviation 12.73 |
| Placebo | Period 2: Change From Baseline in Vital Signs: DBP and SBP | SBP- Day 2 pre-PET scan | -3.0 Millimeter of mercury | Standard Deviation 19.8 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Vital Signs: DBP and SBP | SBP- Day 1 prior to discharge | -6.0 Millimeter of mercury | Standard Deviation 12.19 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Vital Signs: DBP and SBP | DBP-30 minutes post-PET scan | 4.2 Millimeter of mercury | Standard Deviation 6.91 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Vital Signs: DBP and SBP | SBP- 30 minutes post-PET scan | 7.2 Millimeter of mercury | Standard Deviation 7.89 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Vital Signs: DBP and SBP | DBP- Day 1 prior to discharge | -3.6 Millimeter of mercury | Standard Deviation 8.05 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Vital Signs: DBP and SBP | SBP- Day 2 pre-PET scan | -8.6 Millimeter of mercury | Standard Deviation 16.56 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Vital Signs: DBP and SBP | DBP- Day 2 pre-PET scan | -4.8 Millimeter of mercury | Standard Deviation 4.44 |
Primary
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)
Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 2: Change From Baseline in Vital Signs: Heart Rate | 30 minutes post-PET scan | -5.5 Beats per minute | Standard Deviation 6.36 |
| Placebo | Period 2: Change From Baseline in Vital Signs: Heart Rate | Day 1 prior to discharge | 3.0 Beats per minute | Standard Deviation 4.24 |
| Placebo | Period 2: Change From Baseline in Vital Signs: Heart Rate | Day 2 pre-PET scan | -5.5 Beats per minute | Standard Deviation 13.44 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Vital Signs: Heart Rate | 30 minutes post-PET scan | -10.2 Beats per minute | Standard Deviation 3.77 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Vital Signs: Heart Rate | Day 1 prior to discharge | -5.0 Beats per minute | Standard Deviation 6.78 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Vital Signs: Heart Rate | Day 2 pre-PET scan | -9.8 Beats per minute | Standard Deviation 4.97 |
Primary
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)
Population: Intent-to-Treat Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 2: Change From Baseline in Vital Sign: Temperature | 30 minutes post-PET scan | -0.25 Celcius | Standard Deviation 0.919 |
| Placebo | Period 2: Change From Baseline in Vital Sign: Temperature | Day 1 prior to discharge | -0.05 Celcius | Standard Deviation 0.778 |
| Placebo | Period 2: Change From Baseline in Vital Sign: Temperature | Day 2 pre-PET scan | -0.35 Celcius | Standard Deviation 1.061 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Vital Sign: Temperature | 30 minutes post-PET scan | 0.06 Celcius | Standard Deviation 0.537 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Vital Sign: Temperature | Day 1 prior to discharge | 0.34 Celcius | Standard Deviation 0.786 |
| GSK3008348 1000 mcg | Period 2: Change From Baseline in Vital Sign: Temperature | Day 2 pre-PET scan | 0.06 Celcius | Standard Deviation 0.518 |
Primary
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)
Population: Intent-to-Treat Population. Only those participants with available at the indicated time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 2 measurement 2, NCS,n=2,5 | 2 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | 30 minutes measurement 2, NCS,n=2,5 | 1 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 2 measurement 2, CS,n=2,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 1 measurement 1, CS,n=2,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 2 measurement 3, NCS,n=2,5 | 2 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | 30 minutes measurement 2, CS,n=2,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 2 measurement 3, CS,n=2,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 1 measurement 2, NCS,n=2,5 | 1 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 15 measurement 1, NCS,n=3,5 | 1 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Pre-dose measurement 3, CS,n=2,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 15 measurement 1, CS,n=3,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 1 measurement 2, CS,n=2,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 15 measurement 2, NCS,n=3,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | 30 minutes measurement 3, NCS,n=2,5 | 1 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 15 measurement 2, CS,n=3,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 1 measurement 3, NCS,n=2,5 | 1 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 15 measurement 3, NCS,n=3,5 | 1 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | 30 minutes measurement 1, CS,n=2,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 15 measurement 3, CS,n=3,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 1 measurement 3, CS,n=2,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | 30 minutes measurement 3, CS,n=2,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Pre-dose measurement 1, NCS,n=2,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 2 measurement 1, NCS,n=2,5 | 2 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Pre-dose measurement 1, CS,n=2,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | 30 minutes measurement 1, NCS,n=2,5 | 1 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Pre-dose measurement 2, NCS,n=2,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 2 measurement 1, CS,n=2,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Pre-dose measurement 2, CS,n=2,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 1 measurement 1, NCS,n=2,5 | 1 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Pre-dose measurement 3, NCS,n=2,5 | 0 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Pre-dose measurement 1, NCS,n=2,5 | 5 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Pre-dose measurement 3, CS,n=2,5 | 0 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | 30 minutes measurement 1, NCS,n=2,5 | 4 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | 30 minutes measurement 1, CS,n=2,5 | 0 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | 30 minutes measurement 2, CS,n=2,5 | 0 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | 30 minutes measurement 3, NCS,n=2,5 | 4 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | 30 minutes measurement 3, CS,n=2,5 | 0 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 1 measurement 1, NCS,n=2,5 | 4 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 1 measurement 1, CS,n=2,5 | 0 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 1 measurement 2, NCS,n=2,5 | 4 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 1 measurement 2, CS,n=2,5 | 0 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 1 measurement 3, NCS,n=2,5 | 4 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 1 measurement 3, CS,n=2,5 | 0 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 2 measurement 1, NCS,n=2,5 | 3 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 2 measurement 1, CS,n=2,5 | 0 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 2 measurement 2, NCS,n=2,5 | 3 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 2 measurement 2, CS,n=2,5 | 0 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 2 measurement 3, NCS,n=2,5 | 4 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 2 measurement 3, CS,n=2,5 | 0 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 15 measurement 1, NCS,n=3,5 | 3 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 15 measurement 1, CS,n=3,5 | 0 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 15 measurement 2, NCS,n=3,5 | 3 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 15 measurement 2, CS,n=3,5 | 0 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 15 measurement 3, NCS,n=3,5 | 3 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Day 15 measurement 3, CS,n=3,5 | 0 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | 30 minutes measurement 2, NCS,n=2,5 | 4 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Pre-dose measurement 3, NCS,n=2,5 | 5 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Pre-dose measurement 1, CS,n=2,5 | 0 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Pre-dose measurement 2, NCS,n=2,5 | 5 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Findings for 12-lead ECG Parameters | Pre-dose measurement 2, CS,n=2,5 | 0 Participants |
Primary
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)
Population: Intent-to-Treat Population. Only those participants with available at the indicated time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine glucose- 24 hours, 100 mg/dL : n=2,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine proteins- Baseline, Trace: n=2,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine occult blood- Day 15, Trace: n=3,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine proteins- 24 hours, Trace: n=2,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine ketones - 24 hours, 5mg/dL: n=3,4 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine proteins- Day 15, Trace: n=3,5 | 0 Participants |
| Placebo | Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine occult blood- Baseline, Trace: n=2,5 | 0 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine proteins- Day 15, Trace: n=3,5 | 1 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine occult blood- Baseline, Trace: n=2,5 | 1 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine occult blood- Day 15, Trace: n=3,5 | 1 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine glucose- 24 hours, 100 mg/dL : n=2,5 | 1 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine ketones - 24 hours, 5mg/dL: n=3,4 | 2 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine proteins- Baseline, Trace: n=2,5 | 1 Participants |
| GSK3008348 1000 mcg | Period 2: Number of Participants With Abnormal Urinalysis Results by Dipstick | Urine proteins- 24 hours, Trace: n=2,5 | 1 Participants |
Primary
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
Population: Per-Protocol Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 2: Volume of Distribution (VT) of [18F]-FBA-A20FMDV2 in the Whole Lung (Not Corrected for Air Volume) at 30 Minutes Post-dose Compared to Pre-dose | Baseline | 1.664 Milliliter per cubic centimeter(mL/cm^3) | Geometric Coefficient of Variation 19.67 |
| Placebo | Period 2: Volume of Distribution (VT) of [18F]-FBA-A20FMDV2 in the Whole Lung (Not Corrected for Air Volume) at 30 Minutes Post-dose Compared to Pre-dose | 30 minutes post-dose PET scan 1 | 1.572 Milliliter per cubic centimeter(mL/cm^3) | Geometric Coefficient of Variation 8.56 |
| GSK3008348 1000 mcg | Period 2: Volume of Distribution (VT) of [18F]-FBA-A20FMDV2 in the Whole Lung (Not Corrected for Air Volume) at 30 Minutes Post-dose Compared to Pre-dose | Baseline | 1.503 Milliliter per cubic centimeter(mL/cm^3) | Geometric Coefficient of Variation 37.32 |
| GSK3008348 1000 mcg | Period 2: Volume of Distribution (VT) of [18F]-FBA-A20FMDV2 in the Whole Lung (Not Corrected for Air Volume) at 30 Minutes Post-dose Compared to Pre-dose | 30 minutes post-dose PET scan 1 | 1.198 Milliliter per cubic centimeter(mL/cm^3) | Geometric Coefficient of Variation 44.37 |
Secondary
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
Population: Pharmacokinetic Population. Only those participants with data available at the indicated data points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Period 1: Area Under the Plasma Concentration-time Curve From Zero Hours to Infinity (AUC[0-infinity]) After Single Dose Administration of GSK3008348 | 67715.8 Hours*picograms per milliliter | Geometric Coefficient of Variation 80 |
Secondary
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
Population: Pharmacokinetic Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Period 1: Area Under the Plasma Concentration-time Curve From Zero Hours to Time (AUC[0-t]) After Single Dose Administration of GSK3008348 | 64638.3 Hours*picograms per milliliter | Geometric Coefficient of Variation 58 |
Secondary
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
Population: Pharmacokinetic Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Period 1: Maximum Observed Plasma Drug Concentration (Cmax) After Single Dose Administration of GSK3008348 | 14050.4 Picograms per milliliter | Geometric Coefficient of Variation 38 |
Secondary
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
Population: Pharmacokinetic Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Period 1: Terminal Phase Half-life (t1/2) After Single Dose Administration of GSK3008348 | 10.6 Hours | Geometric Coefficient of Variation 21 |
Secondary
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
Population: Pharmacokinetic Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Period 1: Time of Occurrence of Cmax (Tmax) After Single Dose Administration of GSK3008348 | 0.50 Hours |
Secondary
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
Population: Pharmacokinetic Population. Data were not analyzed for AUC(0-infinity) as there were not enough data points collected for a terminal slope required to calculate AUC(0-infinity).
Secondary
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
Population: Pharmacokinetic Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Period 2: AUC(0-t) After Single Dose Administration of GSK3008348 | 66122.5 Hours*picogram per milliliter | Geometric Coefficient of Variation 44 |
Secondary
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
Population: Pharmacokinetic Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Period 2: Cmax After Single Dose Administration of GSK3008348 | 10418.2 Picograms per milliliter | Geometric Coefficient of Variation 31 |
Secondary
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
Population: Pharmacokinetic Population. Data were not analyzed for t1/2 as there were not enough data points collected for a terminal slope required to calculate t1/2.
Secondary
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
Population: Pharmacokinetic Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Period 2: Tmax After Single Dose Administration of GSK3008348 | 0.47 Hours |
Secondary
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
Population: Per-Protocol Population. Only those participants with PET data available at the indicated time points were analyzed (represented by n= X in the category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Period 2: VT of [18F]-FBAA20FMDV2 in the Whole Lung (Not Corrected for Air Volume) Approximately 24 Hours Post-dose Compared to Pre-dose | Baseline, n=2,5 | 1.664 mL/cm^3 | Geometric Coefficient of Variation 19.67 |
| Placebo | Period 2: VT of [18F]-FBAA20FMDV2 in the Whole Lung (Not Corrected for Air Volume) Approximately 24 Hours Post-dose Compared to Pre-dose | 24 hours post-dose PET scan 2, n=1,3 | 1.530 mL/cm^3 | — |
| GSK3008348 1000 mcg | Period 2: VT of [18F]-FBAA20FMDV2 in the Whole Lung (Not Corrected for Air Volume) Approximately 24 Hours Post-dose Compared to Pre-dose | Baseline, n=2,5 | 1.503 mL/cm^3 | Geometric Coefficient of Variation 37.32 |
| GSK3008348 1000 mcg | Period 2: VT of [18F]-FBAA20FMDV2 in the Whole Lung (Not Corrected for Air Volume) Approximately 24 Hours Post-dose Compared to Pre-dose | 24 hours post-dose PET scan 2, n=1,3 | 1.474 mL/cm^3 | Geometric Coefficient of Variation 24.43 |