This is a first time in human (FTIH) study designed to evaluate the safety, tolerability and pharmacokinetic (PK) profile of single and repeat doses of GSK3923868 inhalation powder in both healthy participants and asthmatics. This is a 3-part, randomized, double blind, placebo controlled study of GSK3923868, administered as an inhalation powder blend (GSK3923868 capsules for inhalation) via Mono-dose inhaler in healthy participants (Parts A and B) and in participants with asthma (Part C). The duration of study participation for each part A, B and C will be 11, 9 and 8 weeks, respectively.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
56
GSK3923868 will be available as capsules containing inhalation powder blend to be delivered via Monodose RS01 device.
Placebo to match GSK3923868 will be available as capsule containing inhalation powder to be delivered via Monodose RS01 device.
Participants will receive GSK3923868 and placebo as capsules containing inhalation powder blend to be delivered via Monodose RS01 device.
GSK Investigational Site
Cambridge, United Kingdom
Part A, Cohort-1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs and SAEs were collected. 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. A SAE is any untoward medical occurrence that, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity and/or can result in death. Number of participants with AEs and SAEs assessed in Part A, Cohort-1 from the start of dosing and post-dose washout period (10 days) after treatment periods was reported.
Time frame: Up to Day 43
Part A, Cohort 2: Number of Participants With AEs and SAEs
AEs and SAEs were collected. 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. A SAE is any untoward medical occurrence that, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity and/or can result in death. Number of participants with AEs and SAEs assessed in Part A, Cohort-2 from the start of dosing and post-dose washout period (10 days) after treatment periods was reported.
Time frame: Up to Day 43
Part B: Number of Participants With AEs and SAEs
AEs and SAEs were collected. 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. A SAE is any untoward medical occurrence that, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity and/or can result in death. Number of participants with AEs and SAEs assessed in Part B, Cohort-3 and 4 (repeat dose) of the study were reported. Part B assessed repeat doses of study drug across two parallel cohorts (Cohorts 3 and 4).
Time frame: Up to Day 28
Part C: Number of Participants With AEs and SAEs
AEs and SAEs were collected. 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. A SAE is any untoward medical occurrence that, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity and/or can result in death. Number of participants with AEs and SAEs assessed in Part C, Cohort-5 (repeat dose) of the study were reported.
Time frame: Up to Day 21
Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Laboratory Parameters
The laboratory (lab) measurements included Clinical chemistry and hematology. The parameters evaluated were hemoglobin, leukocytes, lymphocytes/leukocytes, neutrophils/leukocytes, platelets, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red blood cells, reticulocytes, Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Bilirubin, Calcium Corrected for Albumin, Creatinine, Glucose, Potassium and Sodium. Number of participants with clinically significant changes from baseline in clinical chemistry and hematology were reported. Clinical significance was determined by the investigator.
Time frame: From start of the treatment (Day 1) to Day 2 in each treatment period
Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters
The laboratory (lab) measurements included Clinical chemistry and hematology. The parameters evaluated were hemoglobin, leukocytes, lymphocytes/leukocytes, neutrophils/leukocytes, platelets, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red blood cells, reticulocytes, Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Bilirubin, Calcium Corrected for Albumin, Creatinine, Glucose, Potassium and Sodium. Number of participants with clinically significant changes from baseline in clinical chemistry and hematology were reported. Clinical significance was determined by the investigator.
Time frame: From start of the treatment (Day 1) to Day 2 in each treatment period
Part B: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters
The laboratory (lab) measurements included Clinical chemistry and hematology. The parameters evaluated were hemoglobin, leukocytes, lymphocytes/leukocytes, neutrophils/leukocytes, platelets, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red blood cells, reticulocytes, Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Bilirubin, Calcium Corrected for Albumin, Creatinine, Glucose, Potassium and Sodium. Part B assessed repeat doses of study drug across two parallel cohorts (Cohorts 3 and 4). Number of participants with clinically significant changes from baseline in clinical chemistry and hematology were reported. Clinical significance was determined by the investigator.
Time frame: From start of the treatment (Day 1) to Day 18
Part C: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters
The laboratory (lab) measurements included Clinical chemistry and hematology. The parameters evaluated were hemoglobin, leukocytes, lymphocytes/leukocytes, neutrophils/leukocytes, platelets, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red blood cells, reticulocytes, Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Bilirubin, Calcium Corrected for Albumin, Creatinine, Glucose, Potassium and Sodium. Number of participants with clinically significant changes from baseline in clinical chemistry and hematology were reported. Clinical significance was determined by the investigator.
Time frame: From start of the treatment (Day 1) to Day 8
Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead Electrocardiogram (ECG) Findings
Vital signs included systolic and diastolic blood pressure, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Temperature was also measured as a vital sign but did not require positioning or rest prior to measuring. Twelve-lead electrocardiogram were performed in a semi-supine position using an ECG machine that automatically calculates the heart rate and measures PR interval, QRS duration, QT and corrected QT intervals (QTc) intervals. Number of participants with clinically significant changes in parameters for cohort-1 were reported. Clinical significance was determined by the investigator.
Time frame: From start of the treatment (Day 1) to Day 2 in each treatment period
Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings
Vital signs included systolic and diastolic blood pressure, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Temperature was also measured as a vital sign but did not require positioning or rest prior to measuring. Twelve-lead electrocardiogram were performed in a semi-supine position using an ECG machine that automatically calculates the heart rate and measures PR interval, QRS duration, QT and corrected QT intervals (QTc) intervals. Number of participants with clinically significant changes in parameters for cohort-2 were reported. Clinical significance was determined by the investigator.
Time frame: From start of the treatment (Day 1) to Day 2 in each treatment period
Part B: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings
Vital signs included systolic and diastolic blood pressure, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Temperature was also measured as a vital sign but did not require positioning or rest prior to measuring. Twelve-lead electrocardiogram were performed in a semi-supine position using an ECG machine that automatically calculates the heart rate and measures PR interval, QRS duration, QT and corrected QT intervals (QTc) intervals. Part B assessed repeat doses of study drug across two parallel cohorts (Cohorts 3 and 4). Number of participants with clinically significant changes in parameters were reported. Clinical significance was determined by the investigator.
Time frame: From start of the treatment (Day 1) to Day 18
Part C: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings
Vital signs included systolic and diastolic blood pressure, pulse and respiratory rate and were measured with the participant in semi-supine position after 5 minutes rest. Temperature was also measured as a vital sign but did not require positioning or rest prior to measuring. Twelve-lead electrocardiogram were performed in a semi-supine position using an ECG machine that automatically calculates the heart rate and measures PR interval, QRS duration, QT and corrected QT intervals (QTc) intervals. Number of participants with clinically significant changes in parameters for cohort-5 were reported. Clinical significance was determined by the investigator.
Time frame: From start of the treatment (Day 1) to Day 8
Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Spirometry Measurements
Spirometry included forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) for lung function assessment. Number of participants with clinically significant changes in parameters were reported. Clinical significance was determined by the investigator.
Time frame: From start of the treatment (Day 1) to Day 2 in each treatment period
Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Spirometry Measurements
Spirometry included forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) for lung function assessment. Number of participants with clinically significant changes in parameters were reported. Clinical significance was determined by the investigator.
Time frame: From start of the treatment (Day 1) to Day 2 in each treatment period
Part B: Number of Participants With Clinically Significant Changes in Spirometry Measurements
Spirometry included forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) for lung function assessment. Number of participants with clinically significant changes in parameters were reported. Clinical significance was determined by the investigator.
Time frame: From start of the treatment (Day 1) up to Day 18
Part C: Number of Participants With Clinically Significant Changes in Spirometry Measurements
Spirometry included forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) for lung function assessment. Number of participants with clinically significant changes in parameters were reported. Clinical significance was determined by the investigator.
Time frame: From start of the treatment (Day 1) to Day 8
Part A, Cohort 1 and 2: Area Under the Plasma GSK3923868 Concentration Versus Time Curve From Time Zero to Last Quantifiable Concentration (AUC[0-t])
Blood samples were collected for measurement of plasma concentrations of GSK3923868. Area under the concentration-time curve from time zero to the time of the last quantifiable concentration values were reported. Single ascending doses of GSK3923868 were assessed in 2 sequential crossover cohorts (Cohorts 1 and 2) of healthy participants, each with up to 3 treatment periods.
Time frame: Up to Day 2 in each treatment period
Part A, Cohort 1 and 2: Area Under the Plasma GSK3923868 Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-inf])
Blood samples were collected for measurement of plasma concentrations of GSK3923868. Area under the concentration-time curve from time zero extrapolated to infinite time values were reported.
Time frame: Up to Day 2 in each treatment period
Part A, Cohort 1 and 2: Maximum Observed GSK3923868 Plasma Concentration (Cmax)
Cmax was defined as the maximum concentration of drug GSK3923868 in plasma. Blood samples were collected for measurement of plasma concentrations of GSK3923868 for PK analysis.
Time frame: Up to Day 2 in each treatment period
Part A, Cohort 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax)
Tmax was defined as time required to achieve Cmax for drug GSK3923868 in plasma. Blood samples were collected for measurement of plasma concentrations of GSK3923868 for PK analysis.
Time frame: Up to Day 2 in each treatment period
Part B, Cohort 3 and 4: AUC From Time Zero (Predose) to Time Tau (AUC [0-tau]) (Tau=24hours for Once a Day Dosing Regimen) of GSK3923868
Blood samples were collected for measurement of plasma concentrations of GSK3923868 for PK analysis. Area under the concentration-time curve from time zero (predose) to time tau (dosing interval) was reported. Part B assessed repeat doses of study drug across two parallel cohorts (Cohorts 3 and 4).
Time frame: Up to Day 14
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Part B, Cohort 3 and 4: Cmax of GSK3923868
Cmax was defined as the maximum concentration of drug GSK3923868 in plasma. Blood samples were collected for measurement of plasma concentrations of GSK3923868 for PK analysis. Part B assessed repeat doses of study drug across two parallel cohorts (Cohorts 3 and 4).
Time frame: Up to Day 14
Part B, Cohort 3 and 4: Tmax of GSK3923868
Tmax was defined as time required to achieve Cmax for drug GSK3923868 in plasma. Blood samples were collected for measurement of plasma concentrations of GSK3923868 for PK analysis. Part B assessed repeat doses of study drug across two parallel cohorts (Cohorts 3 and 4).
Time frame: Up to Day 14
Part C: AUC (0-tau) (Tau=24 Hours for Once a Day Dosing Regimen) of GSK3923868
Blood samples were collected for measurement of plasma concentrations of GSK3923868 for PK analysis.
Time frame: Up to Day 7
Part C: Cmax of GSK3923868
Cmax was defined as the maximum concentration of drug GSK3923868 in plasma. Blood samples were collected for measurement of plasma concentrations of GSK3923868 for PK analysis.
Time frame: Up to Day 7
Part C: Tmax of GSK3923868
Tmax was defined as time required to achieve Cmax for drug GSK3923868 in plasma. Blood samples were collected for measurement of plasma concentrations of GSK3923868 for PK analysis.
Time frame: Up to Day 7