A Randomised Double-blind, Placebo Controlled, Single Ascending and Repeat Dose, First Time in Human Study in Healthy Participants and Stable Asthmatics to Assess Safety, Tolerability and Pharmacokinetics of GSK3923868 Inhalation Powder
Overview
- Phase
- Phase 1
- Intervention
- GSK3923868
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Sponsor
- GlaxoSmithKline
- Enrollment
- 56
- Locations
- 1
- Primary Endpoint
- Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •For Parts A and B
- •Between 18 and 50 years of age inclusive, at the time of signing the informed consent.
- •Participants who are generally healthy as determined by medical evaluation based on screening medical history, physical examination, vital signs, ECG assessment, pulmonary function testing, laboratory tests and cardiac monitoring.
- •Body weight at least 50.0 kilograms (kg) (110 pounds \[lbs\]) and body mass index (BMI) within the range 18.5 to 32.0 kilograms per meter square (kg/m\^2) (inclusive).
- •Male Participants: A male participant is eligible to participate if they agree to the following during the intervention period and for at least 10 days after the last dose of study intervention: Refrain from donating sperm. Plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remaining abstinent OR must agree to use contraception as detailed below when having sexual intercourse with a woman of childbearing potential who is not currently pregnant: Agree to use a male condom AND female partner to use an additional highly effective contraceptive method with a failure rate of \< 1 percent per year. The participant should also be advised of the benefit for a female partner as a condom may break or leak.
- •Female Participants: A female participant is eligible to participate if she is not pregnant or breastfeeding and is a woman of non-childbearing potential (WONCBP).
- •Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.
- •Inclusion Criteria: Part C
- •Between 18 and 50 years of age inclusive, at the time of signing the informed consent.
- •Participants who are otherwise healthy (other than the acceptable condition of asthma and other mild atopic diseases, including allergic rhinitis and atopic dermatitis) as determined by medical evaluation based on screening medical history, physical examination, vital signs, ECG assessment, pulmonary function testing, laboratory tests and cardiac monitoring.
Exclusion Criteria
- •Part A and B
- •History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data.
- •Alanine transaminase (ALT) and Aspartate Aminotransferase (AST) above upper limit of normal (ULN).
- •Total Bilirubin above ULN (isolated bilirubin above ULN is acceptable if total 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).
- •QTcF \> 450 milliseconds (msec) at screening visit based on the average of triplicate ECGs.
- •Screening ECG measurements meets the following criteria for exclusion: heart rate: males- \<45 or \> 100 beats per minute (bpm); females- \<50 or \> 100 bpm; PR interval: \<120 or \>220 msec; QRS duration: \<70 or \>120 msec; QTcF: \>450 msec.
- •Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
- •Evidence of previous myocardial infarction (does not include ST segment changes associated with re-polarization).
- •Signs and symptoms suggestive of COVID-
Arms & Interventions
Cohort 1:GSK3923868 50 mcg/ 100 mcg/ Placebo
Healthy participants will receive single ascending doses of GSK3923868 or placebo in the planned treatment sequence: GSK3923868 50 mcg/100 mcg/Placebo in treatment periods 1, 2 and 3 respectively. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: GSK3923868
Cohort1:GSK3923868 50 micrograms (mcg)/ Placebo/ 250mcg
Healthy participants will receive single ascending doses of GSK3923868 or placebo in the planned treatment sequence: GSK3923868 50 mcg/Placebo/250 mcg in treatment periods 1, 2 and 3 respectively. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: GSK3923868
Cohort1:GSK3923868 50 micrograms (mcg)/ Placebo/ 250mcg
Healthy participants will receive single ascending doses of GSK3923868 or placebo in the planned treatment sequence: GSK3923868 50 mcg/Placebo/250 mcg in treatment periods 1, 2 and 3 respectively. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: Matching placebo
Cohort1:GSK3923868 50 micrograms (mcg)/ Placebo/ 250mcg
Healthy participants will receive single ascending doses of GSK3923868 or placebo in the planned treatment sequence: GSK3923868 50 mcg/Placebo/250 mcg in treatment periods 1, 2 and 3 respectively. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: Monodose RS01
Cohort 1:GSK3923868 50 mcg/ 100 mcg/ Placebo
Healthy participants will receive single ascending doses of GSK3923868 or placebo in the planned treatment sequence: GSK3923868 50 mcg/100 mcg/Placebo in treatment periods 1, 2 and 3 respectively. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: Matching placebo
Cohort 1:GSK3923868 50 mcg/ 100 mcg/ Placebo
Healthy participants will receive single ascending doses of GSK3923868 or placebo in the planned treatment sequence: GSK3923868 50 mcg/100 mcg/Placebo in treatment periods 1, 2 and 3 respectively. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: Monodose RS01
Cohort 1:GSK3923868 50mcg/ 100mcg/ 250mcg
Healthy participants will receive single ascending doses of GSK3923868 in the planned treatment sequence: GSK3923868 50 mcg/100 mcg/250 mcg in treatment periods 1, 2 and 3 respectively. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: GSK3923868
Cohort 1:GSK3923868 50mcg/ 100mcg/ 250mcg
Healthy participants will receive single ascending doses of GSK3923868 in the planned treatment sequence: GSK3923868 50 mcg/100 mcg/250 mcg in treatment periods 1, 2 and 3 respectively. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: Monodose RS01
Cohort 1:Placebo / GSK3923868 100 mcg/ GSK3923868 250 mcg
Healthy participants will receive single ascending doses of GSK3923868 or placebo in the planned treatment sequence: Placebo/GSK3923868 100 mcg/GSK3923868 250 mcg in treatment periods 1, 2 and 3 respectively. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: GSK3923868
Cohort 1:Placebo / GSK3923868 100 mcg/ GSK3923868 250 mcg
Healthy participants will receive single ascending doses of GSK3923868 or placebo in the planned treatment sequence: Placebo/GSK3923868 100 mcg/GSK3923868 250 mcg in treatment periods 1, 2 and 3 respectively. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: Matching placebo
Cohort 1:Placebo / GSK3923868 100 mcg/ GSK3923868 250 mcg
Healthy participants will receive single ascending doses of GSK3923868 or placebo in the planned treatment sequence: Placebo/GSK3923868 100 mcg/GSK3923868 250 mcg in treatment periods 1, 2 and 3 respectively. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: Monodose RS01
Cohort 2:Placebo / GSK3923868 1000 mcg/ GSK3923868 3000 mcg
Healthy participants will receive single ascending doses of GSK3923868 or placebo in the planned treatment sequence: Placebo/GSK3923868 1000 mcg/GSK3923868 3000 mcg. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: GSK3923868
Cohort 2:Placebo / GSK3923868 1000 mcg/ GSK3923868 3000 mcg
Healthy participants will receive single ascending doses of GSK3923868 or placebo in the planned treatment sequence: Placebo/GSK3923868 1000 mcg/GSK3923868 3000 mcg. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: Matching placebo
Cohort 2:Placebo / GSK3923868 1000 mcg/ GSK3923868 3000 mcg
Healthy participants will receive single ascending doses of GSK3923868 or placebo in the planned treatment sequence: Placebo/GSK3923868 1000 mcg/GSK3923868 3000 mcg. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: Monodose RS01
Cohort 2:GSK3923868 500 mcg/ Placebo/ 3000 mcg
Healthy participants will receive single ascending doses of GSK3923868 or placebo in the planned treatment sequence: GSK3923868 500 mcg/Placebo/3000 mcg. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: GSK3923868
Cohort 2:GSK3923868 500 mcg/ Placebo/ 3000 mcg
Healthy participants will receive single ascending doses of GSK3923868 or placebo in the planned treatment sequence: GSK3923868 500 mcg/Placebo/3000 mcg. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: Matching placebo
Cohort 2:GSK3923868 500 mcg/ Placebo/ 3000 mcg
Healthy participants will receive single ascending doses of GSK3923868 or placebo in the planned treatment sequence: GSK3923868 500 mcg/Placebo/3000 mcg. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: Monodose RS01
Cohort 2:GSK3923868 500 mcg/ 1000 mcg/ Placebo
Healthy participants will receive single ascending doses of GSK3923868 or placebo in the planned treatment sequence: GSK3923868 500 mcg/1000 mcg/Placebo. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: GSK3923868
Cohort 2:GSK3923868 500 mcg/ 1000 mcg/ Placebo
Healthy participants will receive single ascending doses of GSK3923868 or placebo in the planned treatment sequence: GSK3923868 500 mcg/1000 mcg/Placebo. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: Matching placebo
Cohort 2:GSK3923868 500 mcg/ 1000 mcg/ Placebo
Healthy participants will receive single ascending doses of GSK3923868 or placebo in the planned treatment sequence: GSK3923868 500 mcg/1000 mcg/Placebo. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: Monodose RS01
Cohort 2:GSK3923868 500mcg/ 1000mcg/ 3000mcg
Healthy participants will receive single ascending doses of GSK3923868 in the planned treatment sequence: GSK3923868 500 mcg/1000 mcg/3000 mcg. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: GSK3923868
Cohort 2:GSK3923868 500mcg/ 1000mcg/ 3000mcg
Healthy participants will receive single ascending doses of GSK3923868 in the planned treatment sequence: GSK3923868 500 mcg/1000 mcg/3000 mcg. There will be at least 10 days of wash-out period between doses for each participant.
Intervention: Monodose RS01
Cohort 3: Participants receivings repeated doses of GSK3923868
Healthy participants will receive planned repeat doses of 3000 mcg (six capsules) GSK3923868 daily for 14 days
Intervention: GSK3923868
Cohort 3: Participants receivings repeated doses of GSK3923868
Healthy participants will receive planned repeat doses of 3000 mcg (six capsules) GSK3923868 daily for 14 days
Intervention: Monodose RS01
Cohort 4: Participants receiving repeat doses of GSK3923868
Healthy participants will receive planned repeat doses of 3000 mcg (six capsules) GSK3923868 daily for 14 days
Intervention: GSK3923868
Cohort 4: Participants receiving repeat doses of GSK3923868
Healthy participants will receive planned repeat doses of 3000 mcg (six capsules) GSK3923868 daily for 14 days
Intervention: Monodose RS01
Cohort 5: Participants receiving repeat doses of GSK3923868
Participants with stable asthma will receive a planned repeat dosing of 3000 mcg (six capsules) GSK3923868 daily for 7 days
Intervention: GSK3923868
Cohort 5: Participants receiving repeat doses of GSK3923868
Participants with stable asthma will receive a planned repeat dosing of 3000 mcg (six capsules) GSK3923868 daily for 7 days
Intervention: Monodose RS01
Outcomes
Primary Outcomes
Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters
Time Frame: From start of the treatment (Day 1) to Day 2 in each treatment period
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.
Part C: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters
Time Frame: From start of the treatment (Day 1) to Day 8
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.
Part C: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings
Time Frame: From start of the treatment (Day 1) to Day 8
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.
Part B: Number of Participants With Clinically Significant Changes in Spirometry Measurements
Time Frame: From start of the treatment (Day 1) up to Day 18
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.
Part A, Cohort-1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Up to Day 43
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.
Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead Electrocardiogram (ECG) Findings
Time Frame: From start of the treatment (Day 1) to Day 2 in each treatment period
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.
Part B: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings
Time Frame: From start of the treatment (Day 1) to Day 18
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.
Part A, Cohort 2: Number of Participants With AEs and SAEs
Time Frame: Up to Day 43
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.
Part B: Number of Participants With AEs and SAEs
Time Frame: Up to Day 28
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).
Part C: Number of Participants With AEs and SAEs
Time Frame: Up to Day 21
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.
Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Laboratory Parameters
Time Frame: From start of the treatment (Day 1) to Day 2 in each treatment period
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.
Part B: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters
Time Frame: From start of the treatment (Day 1) to Day 18
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.
Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Spirometry Measurements
Time Frame: From start of the treatment (Day 1) to Day 2 in each treatment period
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.
Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings
Time Frame: From start of the treatment (Day 1) to Day 2 in each treatment period
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.
Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Spirometry Measurements
Time Frame: From start of the treatment (Day 1) to Day 2 in each treatment period
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.
Part C: Number of Participants With Clinically Significant Changes in Spirometry Measurements
Time Frame: From start of the treatment (Day 1) to Day 8
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.
Secondary Outcomes
- 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])(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])(Up to Day 2 in each treatment period)
- Part B, Cohort 3 and 4: Cmax of GSK3923868(Up to Day 14)
- 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(Up to Day 14)
- Part A, Cohort 1 and 2: Maximum Observed GSK3923868 Plasma Concentration (Cmax)(Up to Day 2 in each treatment period)
- Part A, Cohort 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax)(Up to Day 2 in each treatment period)
- Part B, Cohort 3 and 4: Tmax of GSK3923868(Up to Day 14)
- Part C: AUC (0-tau) (Tau=24 Hours for Once a Day Dosing Regimen) of GSK3923868(Up to Day 7)
- Part C: Cmax of GSK3923868(Up to Day 7)
- Part C: Tmax of GSK3923868(Up to Day 7)