Leishmaniasis
Conditions
Keywords
GSK3494245, Leishmaniasis, Single Ascending Dose, First Time in Human, Pharmacokinetics
Brief summary
This study is the first to test GSK3494245 in humans, to evaluate its safety, tolerability, and pharmacokinetics (PK) after a single dose. It involves 3 groups of participants and has a crossover design where each participant received a maximum of 3 ascending oral doses of GSK3494245 and 1 placebo dose under fasted conditions. The first 2 Cohorts received up to 3 increasing doses of the drug and 1 dose of a placebo under fasted conditions, within each period, according to the randomization schedule, in a blinded manner. Cohort 3 is comprised of a 2-way crossover which includes 1 dosing regimen under fasted then fed conditions and 1 regimen under fed then fasted conditions in a 1:1 ratio.
Detailed description
The study originally planned to include 2 parts - a single ascending doses (SAD) part and a multiple ascending doses (MAD) part, incorporating a food effect component to investigate the influence of food on the PK of GSK3494245. However, only the SAD part was conducted due to a decision to terminate the study early.
Interventions
DRUGGSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
DRUGPlacebo
Matching placebo capsules were provided
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
The study consists of sequential and cross-over (SAD part, within cohort) groups.
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant must have been 18 to lesser than or equal to (\<=) 55 years of age, at the time of signing the informed consent. * Participant must have been healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A participant with a clinical abnormality or laboratory parameter(s) which was/were not specifically listed in the inclusion or
Exclusion criteria
, outside the normal reference range for the population being studied may have been included only if the Investigator in consultation with the Medical Monitor (if required) agreed and documented that the finding was unlikely to introduce additional risk factors and was not going to interfere with the study procedures. * Body weight greater than or equal to (\>=) 50 kg and body mass index (BMI) within the range 18.5-28 kg per meter square (kg/m\^2) (inclusive). * Male participants only. A male participant with a female partner of reproductive potential must have agreed to use contraception during the intervention period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period. * Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed consent form (ICF) and protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | From Day 1 (first dose) up to 14 days post last dose in each treatment period | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. |
| Number of Participants With Serious Adverse Events (SAEs) | From the signing of the informed consent form (a period starting up to 28 days before the first dose on Day 1) to up to 14 days after the last dose of each treatment period | A SAE is defined as any untoward medical occurrence that, at any dose: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. |
| Number of Participants With Treatment Emergent AEs (TEAEs) and Treatment Emergent SAEs | From Day 1 (first dose) up to 2 days post last dose in each treatment period | A TEAE and treatment emergent SAE is considered any untoward medical occurrence in a clinical study participant, considered by the investigator to have a causal relationship with study treatment. A SAE is defined as any untoward medical occurrence that, at any dose: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. |
| Summary of Change From Baseline in Hematology Parameters: Basophils, Neutrophils, Eosinophils, Lymphocytes, Monocytes and Platelets | At Day 2 and Day 4 in each treatment period compared to Baseline | Blood samples were collected for the assessment of the hematology parameters: basophils, neutrophils, eosinophils, lymphocytes, monocytes and platelets. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. Standard deviation (SD)=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000. |
| Summary of Change From Baseline in Hematology Parameters: Mean Corpuscular Volume | At Day 2 and Day 4 in each treatment period compared to Baseline | Blood samples were collected for the assessment of the hematology parameters: mean corpuscular volume. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000. |
| Summary of Change From Baseline in Hematology Parameters: Mean Corpuscular Hemoglobin | At Day 2 and Day 4 in each treatment period compared to Baseline | Blood samples were collected for the assessment of the hematology parameters: mean corpuscular hemoglobin. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000. |
| Summary of Change From Baseline in Hematology Parameters: Erythrocytes and Reticulocytes | At Day 2 and Day 4 in each treatment period compared to Baseline | Blood samples were collected for the assessment of the hematology parameters: erythrocytes and reticulocytes. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. |
| Summary of Change From Baseline in Hematology Parameters: Hemoglobin | At Day 2 and Day 4 in each treatment period compared to Baseline | Blood samples were collected for the assessment of the hematology parameters: hemoglobin. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. |
| Summary of Change From Baseline in Hematology Parameters: Hematocrit and Reticulocytes | At Day 2 and Day 4 in each treatment period compared to Baseline | Blood samples were collected for the assessment of the hematology parameters: hematocrit and reticulocytes. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. |
| Summary of Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphate (ALP), Aspartate Aminotransferase (AST), Creatine Phosphokinase (CPK), and Gamma Glutamyl Transferase (GGT) | At Day 2 and Day 4 in each treatment period compared to Baseline | Blood samples were collected for the assessment of the clinical chemistry parameters: ALT, ALP, AST, CPK, and GGT. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. |
| Summary of Change From Baseline in Clinical Chemistry Parameters: Albumin, Protein | At Day 2 and Day 4 in each treatment period compared to Baseline | Blood samples were collected for the assessment of the clinical chemistry parameters: albumin and protein. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. |
| Summary of Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Calcium Corrected for Albumin, Glucose, Lactic Acid, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, and Urea | At Day 2 and Day 4 in each treatment period compared to Baseline | Blood samples were collected for clinical chemistry parameters: bicarbonate, calcium corrected for albumin, glucose, lactic acid, magnesium, phosphate, potassium, sodium, triglycerides, urea. Baseline was defined as the last non-missing pre-dose assessment for each cohort. Generally, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments on Day 1 lacked timing, the first recorded was used. If one Day 1 assessment lacked timing, the last available from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, Baseline was set to missing. Change from baseline is defined as post-dose value minus baseline value. SD=0.0000 indicates SD below the detectable assay limit, approximated to 0.0000. |
| Summary of Change From Baseline in Clinical Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin | At Day 2 and Day 4 in each treatment period compared to Baseline | Blood samples were collected for the assessment of the clinical chemistry parameters: bilirubin, creatinine, direct bilirubin. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000. |
| Summary of Change From Baseline in Clinical Chemistry Parameters: C-reactive Protein (CRP) | At Day 2 and Day 4 in each treatment period compared to Baseline | Blood samples were collected for the assessment of the clinical chemistry parameters: CRP. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000. |
| Summary of Change From Baseline in Clinical Chemistry Parameters: pH | At Day 2 and Day 4 in each treatment period compared to Baseline | Blood samples were collected for the assessment of the clinical chemistry parameters: pH. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. |
| Number of Participants With Worst-case Urinalysis Results | From Day 1 up to 14 Days post last dose | Urine samples were collected for the assessment of urinalysis parameters, which include pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick. |
| Summary of Change From Baseline in Physical Examinations: Body Mass Index (BMI) | At Day 2 and Day 4 in each treatment period compared to Baseline | Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000. |
| Summary of Change From Baseline in Vital Signs: Respiratory Rate | At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose) | Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000. |
| Summary of Change From Baseline in Vital Signs: Supine Diastolic Blood Pressure, Supine Systolic Blood Pressure | At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose) | Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000. |
| Summary of Change From Baseline in Vital Signs: Supine Pulse Rate | At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose) | Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000. |
| Summary of Change From Baseline in Vital Signs: Tympanic Membrane Temperature | At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose) | Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000. |
| Summary of Change From Baseline in Physical Examinations: Weight | At Day 2 and Day 4 in each treatment period compared to Baseline | Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000. |
| Summary of Change From Baseline in Electrocardiogram (ECG) Parameters: Heart Rate | At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day (48h), and Day 4 in each treatment period compared to Baseline (pre-dose) | Triplicate 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. |
| Summary of Change From Baseline in ECG Parameters: PR Interval, QRS Interval, QT Interval, Corrected QT (QTc) Interval, QT Interval Corrected Using Bazett's Formula, QT Interval Corrected, Using Fridericia's Formula | At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day (48h), and Day 4 in each treatment period compared to Baseline (pre-dose) | Triplicate 12-lead ECGs were obtained using an ECG machine that automatically measured the PR interval, QRS interval, QT interval, and QTc interval. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. |
| Number of Participants With Abnormal Cardiac Telemetry Findings | Up to 24 hours post first dose on Day 1 | Telemetry is defined as the continuous monitoring of a participant's heart rate and rhythm from a remote location. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Drug Concentration (AUC) Versus Time Curve (AUC[0-t]) of GSK3494245 Following Single Dose Administration, Under Fasting Conditions | At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4) | AUC(0-t) was calculated by using a standard non-compartmental analysis and was defined as area under the curve from time 0 to the last measurable concentration. |
| AUC (0-t) of GSK3494245 Following Single Dose Administration Under Fed Conditions | At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4) | AUC(0-t) was calculated by using a standard non-compartmental analysis and was defined as area under the curve from time 0 to the last measurable concentration. |
| AUC-time Curve From Time Zero to Extrapolated to Infinity (AUC[0-inf]) of GSK3494245 Following Single Dose Administration Under Fasting Condition | At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4) | AUC(0-inf) was calculated by using a standard non-compartmental analysis and was defined as area under the curve from time 0 to infinity. |
| AUC (0-inf) of GSK3494245 Following Single Dose Administration Under Fed Conditions | At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4) | AUC(0-inf) was calculated by using a standard non-compartmental analysis and was defined as area under the curve from time 0 to infinity |
| Maximum Observed Plasma Drug Concentration (Cmax) of GSK3494245 Following Single Dose Administration Under Fasting Conditions | At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4) | Cmax is defined as the maximum concentration of the drug in plasma. |
| Cmax of GSK3494245 Following Single Dose Administration Under Fed Conditions | At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4) | Cmax is defined as the maximum concentration of the drug in plasma. |
| Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK3494245 Following Single Dose Administration Under Fasting Conditions | At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4) | Tmax is defined as a measure of the time required to reach the maximum concentration of the drug. |
| Tmax of GSK3494245 Following Single Dose Administration Under Fed Conditions | At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4) | Tmax is defined as a measure of the time required to reach the maximum concentration of the drug. |
| Apparent Terminal Half-life (t1/2) of GSK3494245 Following Single Dose Administration Under Fasting Conditions | At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4) | t1/2 is defined as the time required by the plasma concentration to decline by 50%. |
| t1/2 of GSK3494245 Following Single Dose Administration Under Fed Conditions | At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4) | t1/2 is defined as the time required by the plasma concentration to decline by 50%. |
| Dose-proportionality Assessment Using AUC(0-inf) Following a Single Dose of GSK3494245 | At Day 1 (post-dose) | A power model was used to assess the dose proportionality. A slope of 1 indicates that PK increased linearly with the dose. A slope greater than 1 indicates that PK increased more than proportionally with increase in the dose. |
| Dose-proportionality Assessment Using Cmax Following Single Dose of GSK3494245 | At Day 1 (post-dose) | A power model was used to assess the dose proportionality. A slope of 1 indicates that PK increased linearly with the dose. A slope greater than 1 indicates that PK increased more than proportionally with increase in the dose. |
Countries
United Kingdom
Contacts
STUDY_DIRECTORGSK Clinical Trials
GlaxoSmithKline
Participant flow
Pre-assignment details
Each cohort was intended to comprise of 4 intervention periods. However, not all dosing periods were completed for each Cohort, due to various reasons including COVID19 lockdown (Cohort 1), PK stopping criteria exceeded (Cohort 2A), and early study termination (Cohort 3A).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 36.1 Years STANDARD_DEVIATION 8.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Sex/Gender, Customized Female | 0 Count of participants |
| Sex/Gender, Customized Male | 2 Count of 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 | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 16 | 0 / 14 | 0 / 15 | 0 / 15 | 0 / 4 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 3 / 4 | 2 / 6 | 3 / 6 | 4 / 8 | 2 / 6 | 1 / 6 | 1 / 6 | 2 / 6 | 1 / 2 | 2 / 6 | 9 / 16 | 7 / 14 | 5 / 15 | 7 / 15 | 3 / 4 | 5 / 6 | 3 / 6 |
| serious Total, serious adverse events | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 2 | 0 / 6 | 1 / 16 | 0 / 14 | 0 / 15 | 0 / 15 | 0 / 4 | 0 / 6 | 0 / 6 |
Outcome results
None listed