Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
First time in human, Stable asthmatics, GSK3923868, Inhalation powder, Phosphatidylinositol 4-kinase beta
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.
Interventions
DRUGGSK3923868
GSK3923868 will be available as capsules containing inhalation powder blend to be delivered via Monodose RS01 device.
DRUGMatching placebo
Placebo to match GSK3923868 will be available as capsule containing inhalation powder to be delivered via Monodose RS01 device.
DEVICEMonodose RS01
Participants will receive GSK3923868 and placebo as capsules containing inhalation powder blend to be delivered via Monodose RS01 device.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Part A will be a single ascending dose escalation study consisting of two sequential cross-over cohorts (Cohorts 1 and 2) in healthy participants. Part B is a repeat dose study consisting of two parallel cohorts (Cohort 3 and 4) in healthy participants. Part C is a repeat dose study consisting of one cohort (Cohort 5) in participants with asthma.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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. * A physician diagnosis of asthma (as defined by the Global Initiative for Asthma \[GINA\], 2020 guidelines) at least 6 months before screening. The reason for diagnosis of asthma should be documented in the participant's source data, including relevant history. * A screening pre-bronchodilator FEV1 \>= 65 percent predicted normal value. * Positive bronchodilator reversibility test defined as an increase in FEV1 of \> 12 percent and \> 200 milliliter (mL) from Baseline, 10 to 15 minutes after administration of 400 micrograms (μg) salbutamol (or equivalent). * Participants with maintained control of their asthma using the permitted medications: short-acting beta agonist (SABA) use only (n=8 participants) and regular treatment with inhaled corticosteroid (ICS) or ICS/long-acting beta agonist (LABA) (including use of Leukotriene Receptor Agonist \[LTRA\]) (n=8 participants). * Body weight at least 50.0 kg (110 lbs) and BMI within the range 18.5 to 32.0 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 WONCBP. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
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-19. * Past or intended use of over-the-counter or prescription medication, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days before the first dose of study intervention, unless in the opinion of the Investigator and the GlaxoSmithKline (GSK) Medical Monitor, the medication will not interfere with the study procedures or compromise participant safety. * Participation in this study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 56 days. * Exposure to more than 4 new chemical entities within 12 months before the first dosing day. * Current enrolment or past participation in a clinical trial and has received an investigational product within the following time period before the first dosing day in this study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). * FEV1 and FVC is \< 80 percent predicted normal value. * Presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention. * Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention. * Positive hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention. * Positive pre-study drug/alcohol screen. * Positive human immunodeficiency virus (HIV) antibody test. * Positive test for COVID-19 infection. * Current or history of drug abuse. * Any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular (AV) block \[2nd degree or higher\], Wolff-Parkinson-White (WPW) syndrome). * Sinus Pauses \> 3 seconds. * Any significant arrhythmia which, in the opinion of the Investigator or GSK Medical monitor, will interfere with the safety for the individual participant. * Non-sustained or sustained ventricular tachycardia (with more than 3 consecutive ventricular ectopic beats). * Regular alcohol consumption within 6 months prior to the study defined as: an average weekly intake of \> 14 units for both males and females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits. * Current or previous use of tobacco- or nicotine-containing products (e.g. cigarettes, nicotine patches or electronic devices) within 6 months before screening and/or have a smoking pack history of \> 5 pack years. * Positive breath carbon monoxide test indicative of recent smoking at screening or each in-house admission to the clinical research unit. * Sensitivity to any of the study interventions, or components thereof (including lactose and magnesium stearate \[MgSt\]), or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study. * Participants with known COVID-19 positive contacts in the past 14 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part C: Number of Participants With Clinically Significant Changes in Spirometry Measurements | 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. |
| Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters | 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 | 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 C: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters | 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 A, Cohort-1: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead Electrocardiogram (ECG) Findings | 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 A, Cohort-2: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings | 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 B: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings | 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 C: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings | 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 A, Cohort-1: Number of Participants With Clinically Significant Changes in Spirometry Measurements | 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 Spirometry Measurements | 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 B: Number of Participants With Clinically Significant Changes in Spirometry Measurements | 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) | 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 2: Number of Participants With AEs and SAEs | 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| Part A, Cohort 1 and 2: Maximum Observed GSK3923868 Plasma Concentration (Cmax) | Up to Day 2 in each treatment period | 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 A, Cohort 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) | Up to Day 2 in each treatment period | 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, 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 | 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). |
| Part B, Cohort 3 and 4: Cmax of GSK3923868 | Up to Day 14 | 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). |
| Part B, Cohort 3 and 4: Tmax of GSK3923868 | Up to Day 14 | 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). |
| Part C: AUC (0-tau) (Tau=24 Hours for Once a Day Dosing Regimen) of GSK3923868 | Up to Day 7 | Blood samples were collected for measurement of plasma concentrations of GSK3923868 for PK analysis. |
| Part C: Cmax of GSK3923868 | Up to Day 7 | 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 C: Tmax of GSK3923868 | Up to Day 7 | 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 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 | 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. |
Countries
United Kingdom
Participant flow
Recruitment details
This was a three-part study with single dose escalation in Part A and repeat dose in Part B and C. Part A and B was conducted in healthy volunteers and Part C was conducted in participants with asthma.
Pre-assignment details
A total of 56 participants (28 in Part A ,17 in Part B and 11 in Part C) were enrolled in this study. This study was conducted at a single center in the United Kingdom.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: GSK3923868 50 Micrograms (mcg)/ Placebo/ 250mcg Healthy participants received single ascending doses of GSK3923868, or placebo matched to GSK3923868 on Day 1 in the planned treatment sequence: GSK3923868 50 mcg/Placebo/250 mcg in treatment periods 1, 2 and 3 respectively. There was a washout of at least 10 days after Treatment Periods 1 and 2. Participants were followed up for 7 to 14 days after last dose in Treatment Period 3. | 5 |
| Cohort 1: GSK3923868 50 mcg/ 100 mcg/ Placebo Healthy participants received single ascending doses of GSK3923868, or placebo matched to GSK3923868 on Day 1 in the planned treatment sequence: GSK3923868 50 mcg/100 mcg/Placebo in treatment periods 1, 2 and 3 respectively. There was a washout of at least 10 days after Treatment Periods 1 and 2. Participants were followed up for 7 to 14 days after last dose in Treatment Period 3. | 3 |
| Cohort 1: GSK3923868 50mcg/ 100mcg/ 250mcg Healthy participants received single ascending doses of GSK3923868 on Day 1 in the planned treatment sequence: GSK3923868 50 mcg/100 mcg/250 mcg in treatment periods 1, 2 and 3 respectively. There was a washout of at least 10 days after Treatment Periods 1 and 2. Participants were followed up for 7 to 14 days after last dose in Treatment Period 3. | 3 |
| Cohort 1: Placebo / GSK3923868 100 mcg/ 250 mcg Healthy participants received single ascending doses of GSK3923868, or placebo matched to GSK3923868 on Day1 in the planned treatment sequence: Placebo/GSK3923868 100 mcg/GSK3923868 250 mcg in treatment periods 1, 2 and 3 respectively. There was a washout of at least 10 days after Treatment Periods 1 and 2. Participants were followed up for 7 to 14 days after last dose in Treatment Period 3. | 3 |
| Cohort 2: Placebo / GSK3923868 1000 mcg/ 3000 mcg Healthy participants received single ascending doses of GSK3923868, or placebo matched to GSK3923868 on Day 1 in the planned treatment sequence: Placebo/GSK3923868 1000 mcg/GSK3923868 3000 mcg in treatment periods 4, 5 and 6 respectively. There was a washout of at least 10 days after Treatment Periods 4 and 5. Participants were followed up for 7 to 14 days after last dose in Treatment Period 6. | 4 |
| Cohort 2: GSK3923868 500 mcg/ Placebo/ 3000 mcg Healthy participants received single ascending doses of GSK3923868, or placebo matched to GSK3923868 on Day 1 in the planned treatment sequence: GSK3923868 500 mcg/Placebo/3000 mcg in treatment periods 4, 5 and 6 respectively. There was a washout of at least 10 days after Treatment Periods 4 and 5. Participants were followed up for 7 to 14 days after last dose in Treatment Period 6. | 3 |
| Cohort 2: GSK3923868 500 mcg/ 1000 mcg/ Placebo Healthy participants received single ascending doses of GSK3923868, or placebo matched to GSK3923868 on Day 1 in the planned treatment sequence: GSK3923868 500 mcg/1000 mcg/Placebo in treatment periods 4, 5 and 6 respectively. There was a washout of at least 10 days after Treatment Periods 4 and 5. Participants were followed up for 7 to 14 days after last dose in Treatment Period 6. | 3 |
| Cohort 2: GSK3923868 500mcg/ 1000mcg/ 3000mcg Healthy participants received single ascending doses of GSK3923868 on Day 1 in the planned treatment sequence: GSK3923868 500 mcg/1000 mcg/3000 mcg in treatment periods 4, 5 and 6 respectively. There was a washout of at least 10 days after Treatment Periods 4 and 5. Participants were followed up for 7 to 14 days after last dose in Treatment Period 6. | 4 |
| Cohort 3 and 4: Placebo Healthy participants received placebo matched to GSK3923868 daily for 14 days. Participants were followed up for 7 to 14 days post last dose of the study treatment. | 4 |
| Cohort 3 and 4: GSK3923868 3000mcg Healthy participants received planned repeat doses of 3000 mcg GSK3923868 daily for 14 days. Participants were followed up for 7 to 14 days post last dose of the study treatment. | 13 |
| Cohort 5: Placebo Participants with stable asthma received placebo matched to GSK3923868 daily for 7 days. Participants were followed up for 7 to 14 days post last dose of the study treatment. | 3 |
| Cohort 5: GSK3923868 3000mcg Participants with stable asthma received a planned repeat dosing of 3000 mcg GSK3923868 daily for 7 days. Participants were followed up for 7 to 14 days post last dose of the study treatment. | 8 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PartA, Cohort1, Treatment Period1(Day1) | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| PartA, Cohort1,Treatment Period2(Day1) | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| PartA, Cohort2: Treatment Period4(Day1) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| PartA, Cohort2: Treatment Period5(Day1) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part B, Cohorts 3 & 4 (Days 1 to 14) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Part C, Cohort 5 (Days 1 to 7) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 5: GSK3923868 3000mcg | Total | Cohort 1: GSK3923868 50 Micrograms (mcg)/ Placebo/ 250mcg | Cohort 1: GSK3923868 50 mcg/ 100 mcg/ Placebo | Cohort 1: GSK3923868 50mcg/ 100mcg/ 250mcg | Cohort 1: Placebo / GSK3923868 100 mcg/ 250 mcg | Cohort 2: Placebo / GSK3923868 1000 mcg/ 3000 mcg | Cohort 2: GSK3923868 500 mcg/ Placebo/ 3000 mcg | Cohort 2: GSK3923868 500 mcg/ 1000 mcg/ Placebo | Cohort 2: GSK3923868 500mcg/ 1000mcg/ 3000mcg | Cohort 3 and 4: Placebo | Cohort 3 and 4: GSK3923868 3000mcg | Cohort 5: Placebo |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized <=18 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 19-64 | 8 Participants | 56 Participants | 5 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 4 Participants | 4 Participants | 13 Participants | 3 Participants |
| Age, Customized >=65 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized ASIAN | 0 Participants | 4 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 1 Participants | 7 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized MIXED RACE | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized WHITE | 7 Participants | 44 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 4 Participants | 2 Participants | 11 Participants | 2 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 56 Participants | 5 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 4 Participants | 4 Participants | 13 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 4 | 0 / 13 | 0 / 3 | 0 / 8 |
| other Total, other adverse events | 3 / 9 | 3 / 9 | 3 / 9 | 6 / 9 | 5 / 9 | 5 / 9 | 5 / 9 | 3 / 9 | 4 / 4 | 12 / 13 | 3 / 3 | 8 / 8 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 9 | 0 / 4 | 0 / 13 | 0 / 3 | 0 / 8 |
Outcome results
Primary
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
Population: The analysis was performed on the safety set that includes all randomized participants who received at least 1 dose of study intervention. Participants were analyzed according to the treatment they received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Placebo | Part A, Cohort-1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 3 Participants |
| Cohort 1: Placebo | Part A, Cohort-1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part A, Cohort-1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part A, Cohort-1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 3 Participants |
| Cohort 1: GSK3923868 100 mcg | Part A, Cohort-1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 3 Participants |
| Cohort 1: GSK3923868 100 mcg | Part A, Cohort-1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cohort 1: GSK3923868 250mcg | Part A, Cohort-1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 6 Participants |
| Cohort 1: GSK3923868 250mcg | Part A, Cohort-1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
Primary
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
Population: The analysis was performed on the safety set that includes all randomized participants who received at least 1 dose of study intervention. Participants were analyzed according to the treatment they received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Placebo | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Laboratory Parameters | Clinical Chemistry | 0 Participants |
| Cohort 1: Placebo | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Laboratory Parameters | Hematology | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Laboratory Parameters | Hematology | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Laboratory Parameters | Clinical Chemistry | 0 Participants |
| Cohort 1: GSK3923868 100 mcg | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Laboratory Parameters | Clinical Chemistry | 0 Participants |
| Cohort 1: GSK3923868 100 mcg | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Laboratory Parameters | Hematology | 0 Participants |
| Cohort 1: GSK3923868 250mcg | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Laboratory Parameters | Clinical Chemistry | 0 Participants |
| Cohort 1: GSK3923868 250mcg | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Laboratory Parameters | Hematology | 0 Participants |
Primary
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
Population: The analysis was performed on the safety set that includes all randomized participants who received at least 1 dose of study intervention. Participants were analyzed according to the treatment they received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Placebo | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Spirometry Measurements | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Spirometry Measurements | 0 Participants |
| Cohort 1: GSK3923868 100 mcg | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Spirometry Measurements | 0 Participants |
| Cohort 1: GSK3923868 250mcg | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Spirometry Measurements | 0 Participants |
Primary
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
Population: The analysis was performed on the safety set that includes all randomized participants who received at least 1 dose of study intervention. Participants were analyzed according to the treatment they received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Placebo | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead Electrocardiogram (ECG) Findings | Vital Signs | 0 Participants |
| Cohort 1: Placebo | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead Electrocardiogram (ECG) Findings | 12-Lead ECG | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead Electrocardiogram (ECG) Findings | 12-Lead ECG | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead Electrocardiogram (ECG) Findings | Vital Signs | 0 Participants |
| Cohort 1: GSK3923868 100 mcg | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead Electrocardiogram (ECG) Findings | 12-Lead ECG | 0 Participants |
| Cohort 1: GSK3923868 100 mcg | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead Electrocardiogram (ECG) Findings | Vital Signs | 0 Participants |
| Cohort 1: GSK3923868 250mcg | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead Electrocardiogram (ECG) Findings | Vital Signs | 0 Participants |
| Cohort 1: GSK3923868 250mcg | Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead Electrocardiogram (ECG) Findings | 12-Lead ECG | 0 Participants |
Primary
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
Population: The analysis was performed on the safety set that includes all randomized participants who received at least 1 dose of study intervention. Participants were analyzed according to the treatment they received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Placebo | Part A, Cohort 2: Number of Participants With AEs and SAEs | SAEs | 0 Participants |
| Cohort 1: Placebo | Part A, Cohort 2: Number of Participants With AEs and SAEs | AEs | 5 Participants |
| Cohort 1: GSK3923868 50 mcg | Part A, Cohort 2: Number of Participants With AEs and SAEs | AEs | 5 Participants |
| Cohort 1: GSK3923868 50 mcg | Part A, Cohort 2: Number of Participants With AEs and SAEs | SAEs | 0 Participants |
| Cohort 1: GSK3923868 100 mcg | Part A, Cohort 2: Number of Participants With AEs and SAEs | AEs | 5 Participants |
| Cohort 1: GSK3923868 100 mcg | Part A, Cohort 2: Number of Participants With AEs and SAEs | SAEs | 0 Participants |
| Cohort 1: GSK3923868 250mcg | Part A, Cohort 2: Number of Participants With AEs and SAEs | SAEs | 0 Participants |
| Cohort 1: GSK3923868 250mcg | Part A, Cohort 2: Number of Participants With AEs and SAEs | AEs | 3 Participants |
Primary
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
Population: The analysis was performed on the Safety Set that includes all randomized participants who received at least 1 dose of study intervention. Participants were analyzed according to the treatment they received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Placebo | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters | Clinical Chemistry | 0 Participants |
| Cohort 1: Placebo | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters | Hematology | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters | Clinical Chemistry | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters | Hematology | 0 Participants |
| Cohort 1: GSK3923868 100 mcg | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters | Hematology | 0 Participants |
| Cohort 1: GSK3923868 100 mcg | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters | Clinical Chemistry | 0 Participants |
| Cohort 1: GSK3923868 250mcg | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters | Hematology | 0 Participants |
| Cohort 1: GSK3923868 250mcg | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters | Clinical Chemistry | 0 Participants |
Primary
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
Population: The analysis was performed on the Safety Set that includes all randomized participants who received at least 1 dose of study intervention. Participants were analyzed according to the treatment they received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Placebo | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Spirometry Measurements | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Spirometry Measurements | 0 Participants |
| Cohort 1: GSK3923868 100 mcg | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Spirometry Measurements | 0 Participants |
| Cohort 1: GSK3923868 250mcg | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Spirometry Measurements | 0 Participants |
Primary
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
Population: The analysis was performed on the safety set that includes all randomized participants who received at least 1 dose of study intervention. Participants were analyzed according to the treatment they received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Placebo | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings | Vital Signs | 0 Participants |
| Cohort 1: Placebo | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings | 12-Lead ECG | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings | 12-Lead ECG | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings | Vital Signs | 0 Participants |
| Cohort 1: GSK3923868 100 mcg | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings | Vital Signs | 0 Participants |
| Cohort 1: GSK3923868 100 mcg | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings | 12-Lead ECG | 0 Participants |
| Cohort 1: GSK3923868 250mcg | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings | Vital Signs | 0 Participants |
| Cohort 1: GSK3923868 250mcg | Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings | 12-Lead ECG | 0 Participants |
Primary
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
Population: The analysis was performed on the safety set that includes all randomized participants who received at least 1 dose of study intervention. Participants were analyzed according to the treatment they received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Placebo | Part B: Number of Participants With AEs and SAEs | AEs | 4 Participants |
| Cohort 1: Placebo | Part B: Number of Participants With AEs and SAEs | SAEs | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part B: Number of Participants With AEs and SAEs | AEs | 12 Participants |
| Cohort 1: GSK3923868 50 mcg | Part B: Number of Participants With AEs and SAEs | SAEs | 0 Participants |
Primary
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
Population: The analysis was performed on the safety set that includes all randomized participants who received at least 1 dose of study intervention. Participants were analyzed according to the treatment they received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Placebo | Part B: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters | Clinical Chemistry | 1 Participants |
| Cohort 1: Placebo | Part B: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters | Hematology | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part B: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters | Clinical Chemistry | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part B: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters | Hematology | 0 Participants |
Primary
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
Population: The analysis was performed on the safety set that includes all randomized participants who received at least 1 dose of study intervention. Participants were analyzed according to the treatment they received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Placebo | Part B: Number of Participants With Clinically Significant Changes in Spirometry Measurements | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part B: Number of Participants With Clinically Significant Changes in Spirometry Measurements | 0 Participants |
Primary
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
Population: The analysis was performed on the safety set that includes all randomized participants who received at least 1 dose of study intervention. Participants were analyzed according to the treatment they received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Placebo | Part B: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings | Vital Signs | 1 Participants |
| Cohort 1: Placebo | Part B: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings | 12-Lead ECG | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part B: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings | Vital Signs | 6 Participants |
| Cohort 1: GSK3923868 50 mcg | Part B: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings | 12-Lead ECG | 0 Participants |
Primary
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
Population: The analysis was performed on the safety set that includes all randomized participants who received at least 1 dose of study intervention. Participants were analyzed according to the treatment they received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Placebo | Part C: Number of Participants With AEs and SAEs | AEs | 3 Participants |
| Cohort 1: Placebo | Part C: Number of Participants With AEs and SAEs | SAEs | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part C: Number of Participants With AEs and SAEs | AEs | 8 Participants |
| Cohort 1: GSK3923868 50 mcg | Part C: Number of Participants With AEs and SAEs | SAEs | 0 Participants |
Primary
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
Population: The analysis was performed on the safety set that includes all randomized participants who received at least 1 dose of study intervention. Participants were analyzed according to the treatment they received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Placebo | Part C: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters | Clinical Chemistry | 1 Participants |
| Cohort 1: Placebo | Part C: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters | Hematology | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part C: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters | Clinical Chemistry | 1 Participants |
| Cohort 1: GSK3923868 50 mcg | Part C: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters | Hematology | 0 Participants |
Primary
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
Population: The analysis was performed on the safety set that includes all randomized participants who received at least 1 dose of study intervention. Participants were analyzed according to the treatment they received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Placebo | Part C: Number of Participants With Clinically Significant Changes in Spirometry Measurements | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part C: Number of Participants With Clinically Significant Changes in Spirometry Measurements | 0 Participants |
Primary
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
Population: The analysis was performed on the safety set that includes all randomized participants who received at least 1 dose of study intervention. Participants were analyzed according to the treatment they received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Placebo | Part C: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings | Vital Signs | 0 Participants |
| Cohort 1: Placebo | Part C: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings | 12-Lead ECG | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part C: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings | Vital Signs | 0 Participants |
| Cohort 1: GSK3923868 50 mcg | Part C: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings | 12-Lead ECG | 0 Participants |
Secondary
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
Population: The analysis was performed on the PK Set that includes all randomized participants who received at least 1 dose of study intervention and had at least 1 non-missing PK assessment (NQ values were to be considered as non-missing values). Participants were analyzed according to the treatment they received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Placebo | Part A, Cohort 1 and 2: Area Under the Plasma GSK3923868 Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-inf]) | 1964.21 h*pg/mL | Geometric Coefficient of Variation 50.59 |
| Cohort 1: GSK3923868 50 mcg | Part A, Cohort 1 and 2: Area Under the Plasma GSK3923868 Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-inf]) | 4125.22 h*pg/mL | Geometric Coefficient of Variation 40.59 |
| Cohort 1: GSK3923868 100 mcg | Part A, Cohort 1 and 2: Area Under the Plasma GSK3923868 Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-inf]) | 8656.56 h*pg/mL | Geometric Coefficient of Variation 34.71 |
| Cohort 1: GSK3923868 250mcg | Part A, Cohort 1 and 2: Area Under the Plasma GSK3923868 Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-inf]) | 22941.62 h*pg/mL | Geometric Coefficient of Variation 24.69 |
| Cohort 2: GSK3923868 1000 mcg | Part A, Cohort 1 and 2: Area Under the Plasma GSK3923868 Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-inf]) | 50504.33 h*pg/mL | Geometric Coefficient of Variation 22.89 |
| Cohort 2: GSK3923868 3000mcg | Part A, Cohort 1 and 2: Area Under the Plasma GSK3923868 Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-inf]) | 146453.53 h*pg/mL | Geometric Coefficient of Variation 24.53 |
Secondary
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
Population: The analysis was performed on the Pharmacokinetic (PK) Set that includes all randomized participants who received at least 1 dose of study intervention and had at least 1 non-missing PK assessment (Non-quantifiable \[NQ\] values were to be considered as non-missing values). Participants were analyzed according to the treatment they received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Placebo | 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]) | 1774.65 Hour*Picograms Per Milliliter (h*pg/mL) | Geometric Coefficient of Variation 48.78 |
| Cohort 1: GSK3923868 50 mcg | 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]) | 3810.3 Hour*Picograms Per Milliliter (h*pg/mL) | Geometric Coefficient of Variation 39.08 |
| Cohort 1: GSK3923868 100 mcg | 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]) | 8111.1 Hour*Picograms Per Milliliter (h*pg/mL) | Geometric Coefficient of Variation 33.37 |
| Cohort 1: GSK3923868 250mcg | 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]) | 22550.14 Hour*Picograms Per Milliliter (h*pg/mL) | Geometric Coefficient of Variation 24.76 |
| Cohort 2: GSK3923868 1000 mcg | 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]) | 49756.36 Hour*Picograms Per Milliliter (h*pg/mL) | Geometric Coefficient of Variation 22.85 |
| Cohort 2: GSK3923868 3000mcg | 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]) | 144519.79 Hour*Picograms Per Milliliter (h*pg/mL) | Geometric Coefficient of Variation 24.37 |
Secondary
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
Population: The analysis was performed on the PK Set that includes all randomized participants who received at least 1 dose of study intervention and had at least 1 non-missing PK assessment (NQ values were to be considered as non-missing values). Participants were analyzed according to the treatment they received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Placebo | Part A, Cohort 1 and 2: Maximum Observed GSK3923868 Plasma Concentration (Cmax) | 370.84 Picograms Per Milliliter (pg/mL) | Geometric Coefficient of Variation 37.29 |
| Cohort 1: GSK3923868 50 mcg | Part A, Cohort 1 and 2: Maximum Observed GSK3923868 Plasma Concentration (Cmax) | 772.49 Picograms Per Milliliter (pg/mL) | Geometric Coefficient of Variation 29.19 |
| Cohort 1: GSK3923868 100 mcg | Part A, Cohort 1 and 2: Maximum Observed GSK3923868 Plasma Concentration (Cmax) | 1811.8 Picograms Per Milliliter (pg/mL) | Geometric Coefficient of Variation 27.96 |
| Cohort 1: GSK3923868 250mcg | Part A, Cohort 1 and 2: Maximum Observed GSK3923868 Plasma Concentration (Cmax) | 4284.89 Picograms Per Milliliter (pg/mL) | Geometric Coefficient of Variation 23.49 |
| Cohort 2: GSK3923868 1000 mcg | Part A, Cohort 1 and 2: Maximum Observed GSK3923868 Plasma Concentration (Cmax) | 9583.02 Picograms Per Milliliter (pg/mL) | Geometric Coefficient of Variation 25.61 |
| Cohort 2: GSK3923868 3000mcg | Part A, Cohort 1 and 2: Maximum Observed GSK3923868 Plasma Concentration (Cmax) | 30985.12 Picograms Per Milliliter (pg/mL) | Geometric Coefficient of Variation 26.09 |
Secondary
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
Population: The analysis was performed on the PK Set that includes all randomized participants who received at least 1 dose of study intervention and had at least 1 non-missing PK assessment (NQ values were to be considered as non-missing values). Participants were analyzed according to the treatment they received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Placebo | Part A, Cohort 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) | 1 Hour (h) |
| Cohort 1: GSK3923868 50 mcg | Part A, Cohort 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) | 1 Hour (h) |
| Cohort 1: GSK3923868 100 mcg | Part A, Cohort 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) | 1 Hour (h) |
| Cohort 1: GSK3923868 250mcg | Part A, Cohort 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) | 1 Hour (h) |
| Cohort 2: GSK3923868 1000 mcg | Part A, Cohort 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) | 1 Hour (h) |
| Cohort 2: GSK3923868 3000mcg | Part A, Cohort 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) | 0.75 Hour (h) |
Secondary
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
Population: The analysis was performed on the PK Set that includes all randomized participants who received at least 1 dose of study intervention and had at least 1 non-missing PK assessment (NQ values were to be considered as non-missing values). Participants were analyzed according to the treatment they received. One participant was withdrawn before dosing on Day 4 and did not contribute to the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Placebo | 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 | Day 1 | 128045.03 h*pg/mL | Geometric Coefficient of Variation 31.39 |
| Cohort 1: Placebo | 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 | Day 14 (n=12) | 144211.68 h*pg/mL | Geometric Coefficient of Variation 29.45 |
Secondary
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
Population: The analysis was performed on the PK Set that includes all randomized participants who received at least 1 dose of study intervention and had at least 1 non-missing PK assessment (NQ values were to be considered as non-missing values). Participants were analyzed according to the treatment they received. One participant was withdrawn before dosing on Day 4 and did not contribute to the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Placebo | Part B, Cohort 3 and 4: Cmax of GSK3923868 | Day 1 | 32342.47 pg/mL | Geometric Coefficient of Variation 24 |
| Cohort 1: Placebo | Part B, Cohort 3 and 4: Cmax of GSK3923868 | Day 14 (n=12) | 31270.98 pg/mL | Geometric Coefficient of Variation 26.17 |
Secondary
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
Population: The analysis was performed on the PK Set that includes all randomized participants who received at least 1 dose of study intervention and had at least 1 non-missing PK assessment (NQ values were to be considered as non-missing values). Participants were analyzed according to the treatment they received. One participant was withdrawn before dosing on Day 4 and did not contribute to the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: Placebo | Part B, Cohort 3 and 4: Tmax of GSK3923868 | Day 1 | 0.75 Hour (h) |
| Cohort 1: Placebo | Part B, Cohort 3 and 4: Tmax of GSK3923868 | Day 14 (n=12) | 1 Hour (h) |
Secondary
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
Population: The analysis was performed on the PK Set that includes all randomized participants who received at least 1 dose of study intervention and had at least 1 non-missing PK assessment (NQ values were to be considered as non-missing values). Participants were analyzed according to the treatment they received. One participant was withdrawn before dosing on Day 7 and did not contribute to the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Placebo | Part C: AUC (0-tau) (Tau=24 Hours for Once a Day Dosing Regimen) of GSK3923868 | Day 1 | 97412.11 h*pg/mL | Geometric Coefficient of Variation 39.87 |
| Cohort 1: Placebo | Part C: AUC (0-tau) (Tau=24 Hours for Once a Day Dosing Regimen) of GSK3923868 | Day 7 (n=7) | 136461.8 h*pg/mL | Geometric Coefficient of Variation 24.21 |
Secondary
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
Population: The analysis was performed on the PK Set that includes all randomized participants who received at least 1 dose of study intervention and had at least 1 non-missing PK assessment (NQ values were to be considered as non-missing values). Participants were analyzed according to the treatment they received. One participant was withdrawn before dosing on Day 7 and did not contribute to the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Placebo | Part C: Cmax of GSK3923868 | Day 1 | 27799.34 pg/mL | Geometric Coefficient of Variation 25.2 |
| Cohort 1: Placebo | Part C: Cmax of GSK3923868 | Day 7 (n=7) | 35484.07 pg/mL | Geometric Coefficient of Variation 11.97 |
Secondary
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
Population: The analysis was performed on the PK Set that includes all randomized participants who received at least 1 dose of study intervention and had at least 1 non-missing PK assessment (NQ values were to be considered as non-missing values). Participants were analyzed according to the treatment they received. One participant was withdrawn before dosing on Day 7 and did not contribute to the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: Placebo | Part C: Tmax of GSK3923868 | Day 1 | 0.758 Hour (h) |
| Cohort 1: Placebo | Part C: Tmax of GSK3923868 | Day 7 (n=7) | 0.75 Hour (h) |