Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
GSK2982772 · 7 trials · 5 indications
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; other important medical events; is associated with liver injury and impaired liver function.
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; other important medical events; is associated with liver injury and impaired liver function.
Clinical chemistry parameters with PCI ranges: aspartate amino transferase (AST), alanine amino transferase (ALT), and alkaline phosphatase (ALP) (high: \>=2 times upper limit of normal \[ULN\] units per liter \[U/L\]); calcium (low: \<2 millimoles per liter \[mmol/L\] and high: \>2.75 mmol/L); glucose (low: \<3 and high: \>9 mmol/L); potassium (low: \<3 and high: \>5.5 mmol/L); sodium (low: \<130 and high: \>150 mmol/L); total bilirubin (high: \>=1.5 times ULN micromoles per liter \[µmol/L\]); high density lipoproteins (HDL) 0.9 to 99.99 mmol/L; low density lipoprotein (LDL) 0 to 3.35 mmol/L; triglycerides 0 to 2.24 mmol/L, creatinine (high: change from Baseline \[BL\]\>44.2 µmol/L). Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change'
Clinical chemistry parameters with their PCI ranges were: AST, ALT, and ALP (high: \>=2 ULN \[U/L\]); calcium (low: \<2 mmol/L and high: \>2.75 mmol/L); glucose (low: \<3 and high: \>9 mmol/L); potassium (low: \<3 and high: \>5.5 mmol/L); sodium (low: \<130 and high: \>150 mmol/L); total bilirubin (high: \>=1.5 times ULN \[µmol/L\]); HDL 0.9 to 99.99 mmol/L; LDL 0.to 3.35 mmol/L; triglycerides 0 to 2.24 mmol/L, creatinine (high: change from BL \>44.2 µmol/L). Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category.
Hematology parameters with their PCI ranges were: hematocrit (high: \>0.54 proportion of red blood cells in blood and low: change from BL\<0.075); hemoglobin (high: \>180 grams per liter \[g/L\] and low: change from BL\<25 g/L); lymphocytes (low: \<0.8 Giga cells/L); platelet count (low: \<100 Giga cells/L and high: \>550 Giga cells/L); neutrophil count (low: \<1.5 Giga cells/L); white blood cell (WBC) count (low: \<3 Giga cells/L and high: \>20 Giga cells/L). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category. Participants were counted twice if the participant had both values that changed 'To Low' and 'To High'.
Hematology parameters with their PCI ranges were: hematocrit (high: \>0.54 proportion of red blood cells in blood and low: change from BL\<0.075); hemoglobin (high: \>180 g/L and low: change from BL\<25 g/L); lymphocytes (low: \<0.8 Giga cells/L); platelet count (low: \<100 Giga cells/L and high: \>550 Giga cells/L); neutrophil count (low: \<1.5 Giga cells/L); WBC count (low: \<3 Giga cells/L and high: \>20 Giga cells/L). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category. Participants were counted twice if the participant had both values that changed 'To Low' and 'To High'.
Urine samples were collected for the assessment of following urine parameters by dipstick method: glucose, protein, blood and ketones. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose, protein, blood and ketones can be read as negative (-), trace, 1+, 2+, 3+, 4+, 5+ indicating proportional concentrations in the urine sample. Number of participants with abnormal results were reported as 'increase to trace' or 'increase to 1+, 2+, 3+, 4+, 5+' relative to BL (Day 1) value. Participants whose value was unchanged (e.g., Trace to Trace), or whose value was decreased, were recorded in the 'No change or Decreased' category.
Urine samples were collected for the assessment of following urine parameters by dipstick method: glucose, protein, blood and ketones. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose, protein, blood and ketones can be read as negative (-), trace, 1+, 2+, 3+, 4+, 5+ indicating proportional concentrations in the urine sample. Number of participants with abnormal results were reported as 'increase to trace' or 'increase to 1+, 2+, 3+, 4+, 5+' relative to BL (Day 1) value. Participants whose value was unchanged (e.g., Trace to Trace), or whose value was decreased, were recorded in the 'No change or Decreased' category.
Vital signs were measured in a semi-supine position after 5 minutes rest and included body temperature, systolic and diastolic blood pressure. The clinical concern range for vital signs were: systolic blood pressure (SBP) (low: \<85 and high: \>160 millimeters of mercury \[mmHg\]); diastolic blood pressure (DBP) (low: \<45 and high: \>100 mmHg). Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category.
Vital signs were measured in a semi-supine position after 5 minutes rest and included body temperature, systolic and diastolic blood pressure. The clinical concern range for vital signs were: SBP (low: \<85 and high: \>160 mmHg); DBP (low: \<45 and high: \>100 mmHg). Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category.
Vital signs were measured in a semi-supine position after 5 minutes rest which included HR. The clinical concern range for HR (low \<40 beats per min \[bpm\] and high \>100 bpm). Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category.
Vital signs were measured in a semi-supine position after 5 minutes rest which included HR. The clinical concern range for HR (low \<40 bpm and high \>100 bpm). Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category.
12-lead ECGs were recorded with the participants in a supine position using an ECG machine. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
12-lead ECGs were recorded with the participants in a supine position using an ECG machine. Number of participants with worst-case clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
An AE was any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE. Number of participants with any nSAE or SAE are presented.
Clinical chemistry parameters included alanine amino transferase (ALT), albumin, alkaline phosphatase, aspartate amino transferase (AST), calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were ALT(high): \>=2\*Upper limit of Normal(ULN) units per liter(U/L), albumin(low): 30 millimoles per liter(mmol/L), alkaline phosphatase(high): \>=2\*ULN U/L, AST(high): \>=2\*ULN U/L, calcium: \<2(low) or \>2.75 mmol/L(high), creatinine (high): increase from Baseline \>44.25 mmol/L, glucose: \<3(low) or \>9 mmol/L(high), potassium: \<3(low) or \>5.5 mmol/L(high), sodium: \<130(low) or \>150 mmol/L(high) and total bilirubin(high): \>=1.5\*ULN micromoles per liter(µmol/L). Participants were counted in the worst case category if their value changes (to low or to high), unless there is no change in their category. Only those clinical chemistry parameters with PCI values (to low and to high) have been presented.
Hematology parameters included hematocrit, hemoglobin, lymphocytes, platelet counts, total neutrophils and white blood cells (WBCs). PCI ranges were \< 0.075 (decrease from baseline) or \>0.54 proportion of red blood cells in blood (high) for hematocrit, \<25 (low) or \>180 grams per liter (g/L) (high) for hemoglobin, \<0.8 x10\^9 cells per liter (cells/L) for lymphocytes (low), \<100 (low) or \>550 x10\^9 cells/L(high) for platelets, \<1.5 x10\^9 cells/L (low) for total neutrophils and \< 3 (low) or \>20 x10\^9 cells/L (high) for WBCs. Participants were counted in the worst case category that their value changes (to low or to high), unless there is no change in their category. Only those hematology parameters with PCI values (to low and to high) have been presented.
Urine samples were collected to assess glucose, ketones, occult blood and protein by dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters glucose, ketones, occult blood and protein were categorized as 'any increase from Baseline', which imply any increase in their concentrations in the urine sample. Only participants with worst case any increase from Baseline values are presented.
Urine samples were collected to assess glucose, ketones, occult blood and protein by dipstick method. Microscopy was performed only on urine samples showing an abnormality on the dipstick. Microscopy was performed for hyaline casts, red blood cells and white blood cells. Results for microscopy parameters hyaline casts, red blood cells and white blood cells were categorized as 'any increase from Baseline', which imply any increase in their count in the urine sample. Only participants with worst case any increase from Baseline values are presented.
12- lead ECG was measured on each day using an ECG machine that automatically calculated the heart rate and measured PR interval, QRS duration, QT interval, QT interval corrected for heart rate according to either Bazett's formula (QTcB) and QT interval corrected for heart rate according to Fridericia's formula (QTcF). ECG was measured in semi-supine or supine position after 5 minutes rest. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
12- lead ECG was measured on each day using an ECG machine that automatically calculated the heart rate and measured PR interval, QRS duration, QT interval QTcB and QTcF. ECG was measured in semi-supine or supine position after 5 minutes rest. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
SBP and DBP were measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Respiratory rate was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Body temperature was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the latest pre-dose assessment (Day 1 pre-dose). Change from Baseline was calculated by subtracting post-dose value from Baseline value.
Vital sign-heart rate was planned to be assessed as a measure of safety and tolerability.
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is associated with liver injury and impaired liver function or any other situations as per medical or scientific judgment. Safety Population comprised of all participants who received at least one dose of study treatment.
Blood samples were collected for analysis of clinical chemistry parameters. Clinical concern ranges were \>=2x Upper Limit of Normal (ULN) units per liter (U/L) for alanine aminotransferase (ALT), \<30 millimoles per liter (mmol/L) for albumin, \>=2x ULN U/L for alkaline phosphatase, \>=2x ULN U/L for aspartate aminotransferase (AST), \<2 or \>2.75 mmol/L for Calcium, \>44.2 mmol/L for Creatinine, \<3 or \>9 mmol/L for Glucose, \<3 or\>5.5 mmol/L for Potassium, \<130 or \>150 mmol/L for Sodium, and \>=1.5xULN micromoles per liter for total bilirubin. Participants were counted in worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (example given \[e.g.\], High to High), or whose value became normal, were recorded in "To Normal or No Change" category. Participants were counted twice if they had values that changed 'To Low' and 'To High', Baseline is defined as the latest pre-dose assessment.
Blood samples were collected for analysis of hematology parameters. Clinical concern ranges were \>0.54 calculated as proportion of red blood cells in blood for Hematocrit, \>180 grams per liter for Hemoglobin, \<0.8 x10\^9 cells per liter for Lymphocytes, \<1.5 x10\^9 cells per liter for Neutrophil count, \<100 or \>550 x10\^9 cells per liter for Platelet count and \<3 or \>20 x10\^9 cells per liter White Blood Cell count. Participants were counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants were counted twice if they had values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment.
Urine samples were collected for measurement of urine pH at indicated time points. pH is a measure of hydrogen ion concentration and used to determine the acidity or alkalinity of urine. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Urine samples were collected to analyze specific gravity of urine. Specific gravity, is a measure of urine concentration and is measured using a chemical test. Specific gravity measurements provide a comparison of the amount of substances dissolved in urine as compared to pure water. If there were no solutes present, the specific gravity of urine would be 1.000 the same as pure water. Specific gravity between 1.002 and 1.035 could be considered as normal. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Blood pressure was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Heart rate was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Respiratory rate was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Body temperature was measured at indicated time points in supine or semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment. Change from Baseline is defined as any post-dose visit value minus Baseline value.
Single 12-lead electrocardiograms were obtained at indicated time points during the study using an electrocardiogram machine that automatically calculates the heart rate and measures PR, QRS, QT, QT interval corrected for heart rate (QTc) using Bazett's formula (QTcB) intervals and QTc using Fridericia's formula (QTcF). The abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Baseline is defined as the latest pre-dose assessment. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. The number of participants with normal and abnormal electrocardiogram findings at any time post-Baseline visit has been presented.
The Psoriasis area severity index (PASI) is a standard tool for assessing the severity of psoriasis that considers the overall severity of erythema, induration, and scaling (each scored separately), and the extent of body surface area (BSA) affected with psoriasis. The 3 clinical signs are each graded on a 5-point scale (0=none to 4=severe) and the percent BSA affected is scored on a 7-point scale (0= 0% skin with psoriasis to 6= ≥ 90% skin with psoriasis). The individual scores are multiplied by a weighted factor for each body region; the sum of these scores gives the overall PASI score. The PASI is a composite scoring assessed by the investigator for the severity of lesions and the area affected into a single score with a range of 0 (no disease) to 72 (maximal disease), with higher scores representing greater severity of psoriasis. Note: The 95% credible interval (CrI) was reported as a method of dispersion.
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 defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. Safety population comprised of all participants who have received at least one dose of study treatment. This population was used for the safety analyses.
Blood samples were collected for the analysis of clinical chemistry parameters including: glucose, calcium, cholesterol, chloride, high density lipoprotein (HDL) cholesterol, potassium, low density lipoprotein (LDL) cholesterol, phosphate, sodium, triglycerides and urea. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Blood samples were collected for the analysis of clinical chemistry parameters including: albumin and protein. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Blood samples were collected for the analysis of clinical chemistry parameters including: ALP, ALT, AST, CK, GGT and LDH. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Blood samples were collected for the analysis of clinical chemistry parameter: amylase. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Blood samples were collected for the analysis of clinical chemistry parameters:direct bilirubin, bilirubin, creatinine and urate. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Blood samples were collected for the analysis of clinical chemistry parameter: CRP. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Blood samples were collected for the analysis of hematology parameter: hematocrit. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Blood samples were collected for the analysis of hematology parameter: hemoglobin. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Blood samples were collected for the analysis of hematology parameter: erythrocyte MCH. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Blood samples were collected for the analysis of hematology parameter: erythrocyte MCV. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Blood samples were collected for the analysis of hematology parameter: erythrocytes. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Blood samples were collected for the analysis of hematology parameter: percentage reticulocytes. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Blood samples were collected for the analysis of hematology parameters including platelet count and leukocytes. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Blood samples were collected for the analysis of hematology parameters including neutrophils/leukocytes, lymphocytes/leukocytes, monocytes/leukocytes, eosinophils/leukocytes and basophils/leukocytes. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Urine samples were collected to assess urine bilirubin, urine glucose, urine ketones, urine occult blood, urine protein and urine urobilinogen by dipstick test. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameter of urine bilirubin, urine occult blood, urine glucose, urine ketones, urine protein and urine urobilinogen can be read as negative (-) and trace (+-) indicating proportional concentrations in the urine sample.
Full 12-lead ECGs were recorded in participant using an automated ECG machine. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Full 12-lead ECGs were recorded in participants using an automated ECG machine and measured PR, QRS, QT and QTcF intervals. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Continuous cardiac telemetry was performed and number of participants with abnormal clinically significant and not clinically significant values are presented.
Pulse rate of participants were measured at indicated time points in supine position after 5 minutes rest. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Temperature of participants were measured at indicated time points in supine position after 5 minutes rest. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Neurological examinations including: mental status, gait, balance, coordination, cranial nerves, motor power, reflexes, and sensory system (light touch and pain) were assessed in participants specified time points.
An AE is any untoward medical occurrence in a clinical study subjects, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.
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. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE.
Blood samples were collected from participants for the analysis of following clinical chemistry parameters: alanine amino transferase (ALT), albumin, alkaline phosphatase, aspartate amino transferase (AST), calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were \>=2 times Upper Limit of Normal (ULN) units per liter (U/L) for ALT, \<30 grams per liter (g/L) for albumin, \>=2 times ULN U/L for alkaline phosphatase, \>=2 times ULN U/L for AST, \<2 or \>2.75 millimoles per liter (mmol/L) for calcium, \>44.2 micromoles per liter (µmol/L) for creatinine, \<3 or \>9 mmol/L for glucose, \<3 or \>5.5 mmol/L for potassium, \<130 or \>150 mmol/L for sodium and \>=1.5 times ULN for total bilirubin. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Blood samples were collected from participants for the analysis of following clinical chemistry parameters: ALT, albumin, alkaline phosphatase, AST, calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were \>=2 times ULN U/L for ALT, \<30 g/L for albumin, \>=2 times ULN U/L for alkaline phosphatase, \>=2 times ULN U/L for AST, \<2 or \>2.75 mmol/L for calcium, \>44.2 µmol/L for creatinine, \<3 or \>9 mmol/L for glucose, \<3 or \>5.5 mmol/L for potassium, \<130 or \>150 mmol/L for sodium and \>=1.5 times ULN for total bilirubin. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, lymphocytes, platelet count, total neutrophils and white blood cell (WBC) counts. PCI ranges were \>0.54 or \< 0.075 proportion of red blood cells (RBC) in blood for hematocrit, \<25 or \>180 g/L for hemoglobin, 0.8 x10\^9 cells/L for lymphocytes, \<1.5 x10\^9 cells/L for neutrophils, \<100 or \>550 x10\^9 cells/L for platelets and \<3 or 20\> x 10\^9 cells per liter WBC. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, lymphocytes, platelet count, total neutrophils and WBC counts. PCI ranges were \>0.54 or \< 0.075 proportion of RBC in blood for hematocrit, \<25 or \>180 g/L for hemoglobin, 0.8 x10\^9 cells/L for lymphocytes, \<1.5 x10\^9 cells/L for neutrophils, \<100 or \>550 x10\^9 cells/L for platelets and \<3 or 20\> x 10\^9 cells per liter WBC. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Urine samples were collected from participants for analysis of following parameters: cellular casts, granular casts, hyaline casts, RBC and WBC and were counted as cells per high-power field (cells/HPF). The number of participants with cells in urine has been presented.
Urine samples were collected from participants for analysis of following parameters: cellular casts, granular casts, hyaline casts, RBC and WBC and were counted as cells per high-power field (cells/HPF). The number of participants with cells in urine has been presented.
Vital signs were measured in a supine position after 5 minutes rest. The PCI criteria for vital signs included: systolic blood pressure \<85 and \>160 millimeters of mercury \[mmHg\]), diastolic blood pressure \<45 mmHg and \>100 mmHg, heart rate \<40 and \>100 beats per minute, body temperature \<=35.5 and \>=37.8 degrees Celsius and respiration rate \<=8 and \>=20 breaths per minute. Data of participants with potential clinical importance has been reported.
Vital signs were measured in a supine position after 5 minutes rest. The PCI criteria for vital signs included: systolic blood pressure \<85 and \>160 mmHg, diastolic blood pressure \<45 mmHg and \>100 mmHg, heart rate \<40 and \>100 beats per minute, body temperature \<=35.5 and \>=37.8 degrees Celsius and respiration rate \<=8 and \>=20 breaths per minute. Data of participants with potential clinical importance has been reported.
12-lead ECG's were obtained in the supine position after 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
12-lead ECG's were obtained in the supine position after 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant and not clinically significant abnormal ECG findings have been presented. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
AEs and SAEs will be collected from the start of Study Treatment until the follow-up contact
Laboratory assessments will include analysis of hematology parameters, clinical chemistry, routine urinalysis, lipid panel (Part B Only) and other screening Tests
12-lead ECGs will be obtained at each time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Triplicate 12-lead ECGs will be obtained pre-dose on Day 1 and Day 14 (Part B only).
Vital signs will be measured in semi-supine position after short period of time (e.g., 5 to 10 minutes rest) and will include systolic and diastolic blood pressure, temperature, pulse rate, pulse oximetry (SpO2), and respiratory rate. Triplicate vital signs will be obtained pre-dose on Day 1 and Day 14 (Part B only)
A complete physical examination will include assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. Weight will also be measured and recorded. A brief physical examination will include assessments of the skin, lungs, cardiovascular system, abdomen (liver and spleen), and assessment for lymphadenopathy
| Arm | Type | Description |
|---|---|---|
| GSK2982772 in Part A double-blind phase | EXPERIMENTAL | Subjects will receive GSK2982772 60 mg orally three times daily (approximately 8 hours apart) for 42 days (6 weeks). |
| Placebo in Part A double-blind phase | PLACEBO_COMPARATOR | Subjects will receive placebo orally three times daily (approximately 8 hours apart) for 42 days (6 weeks). |
| GSK2982772 in Part B open label extension phase | EXPERIMENTAL | Subjects from GSK2982772 and placebo arm who complete Part A study will move to Part B open-label extension phase. All subjects will receive GSK2982772 60 mg three times daily (approximately 8 hours apart) for 42 days (6 weeks). |
| Subjects receiving GSK2982772 60 mg | EXPERIMENTAL | Enrolled subjects will receive GSK2982772 60 mg thrice daily (approximately 8 hours apart) for 84 days. |
| Subjects receiving Placebo | EXPERIMENTAL | Enrolled subjects will receive placebo thrice daily (approximately 8 hours apart) for 84 days. |
| GSK2982772 receivers in Cohort 1 | EXPERIMENTAL | Randomized subjects will receive GSK2982772 BID (approximately 12 hours apart) via oral route for 84 days. |
| Placebo receivers in Cohort 1 | PLACEBO_COMPARATOR | Randomized subjects will receive placebo BID via oral route for 84 days. |
| GSK2982772 receivers in Cohort 2 | EXPERIMENTAL | Randomized subjects will receive GSK2982772 TID (approximately 8 hours apart) via oral route for 84 days |
| Placebo receivers in Cohort 2 | PLACEBO_COMPARATOR | Randomized subjects will receive placebo TID via oral route for 84 days. |
| Participants receiving GSK2982772 960 mg | EXPERIMENTAL | Participants will receive GSK2982772 960 mg oral tablets once daily for 12 weeks. |
| Participants receiving placebo | PLACEBO_COMPARATOR | Participants will receive GSK2982772 matching placebo oral tablets once daily for 12 weeks. |
| Sequence 1: Placebo TID then 60 TID then 120 TID then 240 TID | EXPERIMENTAL | The eligible subjects in this arm will receive placebo TID in TP1, GSK2982772 60 mg TID in TP2, GSK2982772 120mg TID in TP3 and GSK2982772 240 mg TID in TP4. GSK2982772 or placebo will be administered at 0 hour (the first dosing), 7 hours (the second dosing) and 14 hours (the third dosing) on Day 1 in each TP. Subjects will fast overnight for 8 hours before first dose. Each TP will be followed by a washout period of at least 7 days, for each subject. |
| Sequence 2: 60 TID then Placebo TID then 120 TID then 240 TID | EXPERIMENTAL | The eligible subjects in this arm will receive GSK2982772 60 mg TID in TP1, placebo TID in TP2, GSK2982772 120mg TID in TP3 and GSK2982772 240 mg TID in TP4. GSK2982772 or placebo will be administered at 0 hour (the first dosing), 7 hours (the second dosing) and 14 hours (the third dosing) on Day 1 in each TP. Subjects will fast overnight for 8 hours before first dose. Each TP will be followed by a washout period of at least 7 days, for each subject. |
| Sequence 3: 60 TID then 120 TID then Placebo TID then 240 TID | EXPERIMENTAL | The eligible subjects in this arm will receive GSK2982772 60 mg TID in TP1, GSK2982772 120mg TID in TP2, placebo TID in TP3 and GSK2982772 240 mg TID in TP4. GSK2982772 or placebo will be administered at 0 hour (the first dosing), 7 hours (the second dosing) and 14 hours (the third dosing) on Day 1 in each TP. Subjects will fast overnight for 8 hours before first dose. Each TP will be followed by a washout period of at least 7 days, for each subject. |
| Sequence 4: 60 TID then 120 TID then 240 TID then Placebo TID | EXPERIMENTAL | The eligible subjects in this arm will receive GSK2982772 60 mg TID in TP1, GSK2982772 120mg TID in TP2, GSK2982772 240 mg TID in TP3 and placebo TID in TP4. GSK2982772 or placebo will be administered at 0 hour (the first dosing), 7 hours (the second dosing) and 14 hours (the third dosing) on Day 1 in each TP. Subjects will fast overnight for 8 hours before first dose. Each TP will be followed by a washout period of at least 7 days, for each subject. |
| Subjects receiving treatment sequence ABC in cohort 1: Part A | EXPERIMENTAL | Eligible subjects will be randomized to receive treatment sequence ABC in Part A; A= GSK2982772 120 mg TID, B= GSK2982772 240 mg TID, and C= GSK2982772 360 mg BID. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens. |
| Subjects receiving treatment sequence ABP in cohort 1: Part A | EXPERIMENTAL | Eligible subjects will be randomized to receive treatment sequence ABP in Part A; A= GSK2982772 120 mg TID, B= GSK2982772 240 mg TID, and P= Placebo. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens. |
| Subjects receiving treatment sequence APC in cohort 1: Part A | EXPERIMENTAL | Eligible subjects will be randomized to receive treatment sequence APC in Part A; A= GSK2982772 120 mg TID, P= Placebo and C= GSK2982772 360 mg BID. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens. |
| Subjects receiving treatment sequence PBC in cohort 1: Part A | EXPERIMENTAL | Eligible subjects will be randomized to receive treatment sequence PBC in Part A; P= Placebo, B= GSK2982772 240 mg TID and C= GSK2982772 360 mg BID. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens. |
| Subjects receiving GSK2982772 120 mg TID in cohort 2 : Part B | EXPERIMENTAL | Eligible subjects will receive GSK2982772 oral capsule with a dose of 120 mg TID for 14 days in Part B. |
| Subjects receiving GSK2982772 120 mg TID in cohort 3 : Part B | EXPERIMENTAL | Eligible subjects will receive GSK2982772 oral capsule with a dose of 120 mg TID for 14 days in Part B. |
| Subjects receiving GSK2982772 240 mg TID in cohort 4: Part B | EXPERIMENTAL | Eligible subjects will receive GSK2982772 oral capsule with a dose of 240 mg TID for 14 days in Part B. |
| Subjects receiving GSK2982772 360 mg BID in cohort 5: Part B | EXPERIMENTAL | Eligible subjects will receive GSK2982772 oral capsule with a dose of 360 mg BID for 14 days in Part B. |
| Subjects receiving placebo in cohort 2 : Part B | PLACEBO_COMPARATOR | Subjects will receive placebo oral capsule for 14 days in Part B. |
| Subjects receiving placebo in cohort 3 : Part B | PLACEBO_COMPARATOR | Subjects will receive placebo oral capsule for 14 days in Part B. |
| Subjects receiving placebo in cohort 4 : Part B | PLACEBO_COMPARATOR | Subjects will receive placebo oral capsule for 14 days in Part B. |
| Subjects receiving placebo in cohort 5: Part B | PLACEBO_COMPARATOR | Subjects will receive placebo oral capsule for 14 days in Part B. |
| Cohort 1: GSK2982772 Single Ascending Dose (Part A) (0.1-10mg) | EXPERIMENTAL | Eight subjects will be randomized equally (1:1:1:1) to one of the 4 placebo-controlled dose sequences with 2 subjects in each sequence and each subject having four dose periods (3 active dose of GSK2982772 + 1 placebo dose). The subjects will fast overnight from Day -1 to Day 1 of the treatment period. Two of the 8 subjects will be randomized to the dosing on Day 1 as sentinel dosing. Assuming adequate safety in the judgment of the Principal Investigator (e.g., vital signs, ECGs, and adverse events) through approximately 24 hours; the remaining 6 subjects may be randomized to dosing on the following day. Subjects will receive single planned doses of GSK2982772 as 0.1, 0.5, 2.5, and 10mg. A sequential design will be used including approximately weekly dose escalations while allowing for a sufficient washout period. The proposed doses may be adjusted based on emerging safety and PK |
| Cohort 2: GSK2982772 Single Ascending Dose (Part A) (40-240mg) | EXPERIMENTAL | Eight subjects will be randomized equally to one of the 4 placebo-controlled dose sequences with 2 subjects in each sequence and each subject having 4 dose periods (3 active dose of GSK2982772 +1 placebo dose). The subjects will fast overnight from Day -1 to Day 1 of the treatment period. Two of the 8 subjects will be randomized to the dosing on Day 1 as sentinel dosing. Assuming adequate safety in the judgment of the Principal Investigator (e.g., vital signs, ECGs, and adverse events) through 24 hours; the remaining 6 subjects may be randomized to dosing on the following day. Subjects will receive single planned doses of GSK2982772 as 40, 100, 180, and 240 mg. A sequential design with weekly dose escalations and sufficient washout period will be used. The proposed doses may be adjusted based on emerging safety and PK. After the completion of the fasted treatment periods, subjects will receive a high fat meal within 30 minutes of dosing with GSK2982772 during a final treatment period. |
| Cohort 3: GSK2982772 Repeat Dose (Part B) | EXPERIMENTAL | Twelve subjects will be randomized to repeat doses of GSK2982772 or placebo in a 3:1 ratio. The subjects will fast overnight from Day -1 to Day 1 and overnight from Day 13 to Day 14. The selection of appropriate daily doses will be performed upon consideration of available safety and tolerability and PK data from Part A. Once-daily dosing is planned, but twice-daily dosing may be considered based upon the exposure observed in the Part A data |
| Cohort 4: GSK2982772 Repeat Dose (Part B) | EXPERIMENTAL | Twelve subjects will be randomized to repeat doses of GSK2982772 or placebo in a 3:1 ratio. The subjects will fast overnight from Day -1 to Day 1 and overnight from Day 13 to Day 14. The selection of appropriate daily doses will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts in Part B. Once-daily dosing is planned, but twice-daily dosing may be considered based upon the exposure observed in Part A or any preceding repeat dose cohorts in Part B |
| Cohort 5: GSK2982772 Repeat Dose (Part B) | EXPERIMENTAL | Twelve subjects will be randomized to repeat doses of GSK2982772 or placebo in a 3:1 ratio. The subjects will fast overnight from Day -1 to Day 1 and overnight from Day 13 to Day 14. The selection of appropriate daily doses will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts in Part B. Once-daily dosing is planned, but twice-daily dosing may be considered based upon the exposure observed in the Part A or any preceding repeat dose cohorts in Part B. |
| Cohort 6: GSK2982772 Single Ascending Dose (Part A) | EXPERIMENTAL | This additional cohort in Part A of the study will only be conducted to allow for evaluation of additional dose levels or repeated evaluation of a dose level already studied. Doses will be selected based on the safety, tolerability, and PK data from Part A and/or previous Part B cohorts. Eight subjects will be randomized equally (1:1:1:1) to one of the 4 placebo-controlled dose sequences with 2 subjects in each sequence and each subject having four dose periods (3 active dose of GSK2982772 + 1 placebo dose). The selection of appropriate daily doses will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts in Part B. |
| Cohort 7: GSK2982772 Repeat Dose (Part B) | EXPERIMENTAL | This additional cohort in Part B of the study will only be conducted to allow for evaluation of additional dose levels or repeated evaluation of a dose level already studied Doses will be selected based on the safety, tolerability, and PK data from Part A and/or previous Part B cohorts. Twelve subjects will be randomized to repeat doses of GSK2982772 or placebo in a 3:1 ratio. The selection of appropriate daily doses will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts in Part B. |
| Name | Type | Description |
|---|---|---|
| GSK2982772 | DRUG | GSK2982772 is available as a 30 mg white to almost white, round film coated tablet which will be administered as two tablets three times a day as directed. |
| Placebo | DRUG | Placebo is available as a white to almost white, round film coated tablet which will be administered as two tablets three times a day as directed. |
| GSK2982772 60 mg | DRUG | GSK2982772 is available as a 30 mg white to almost white, round film coated tablet which will be administered as two tablets thrice daily as directed. |
| GSK2982772 capsule | DRUG | GSK2982772 will be available as size 00, white, opaque capsule containing white to almost white Solid (120 mg maximum fill per capsule). It will be administered orally with water to receive total dose of 120 mg, 240 mg or 360 mg per randomization. |
| Placebo capsule | DRUG | Placebo will be available as size 00, white, opaque capsule containing white to almost white Solid. It will be administered orally with water. |
| GSK2982772 solution | DRUG | Clear, colorless solution containing GSK2982772 in water with 5% ethanol (0.1mg/mL). Administered orally in required volumes for dosing less than 5mg |
| Placebo solution | DRUG | Clear, colorless solution containing placebo in water with 5% ethanol (0.1mg/mL). Administered orally in required volumes for dosing less than 5mg |
Inclusion Criteria: * Between 18 and 75 years of age inclusive, at the time of signing the informed consent. * Subjects that do not have any medical conditions, other than active UC, that in the opinion of the Investigator put the subject at unacceptable risk or interfere with study assessments or ...
GSK2982772 is an investigational small molecule being developed for autoimmune diseases, including psoriasis, ulcerative colitis, inflammatory bowel diseases, and rheumatoid arthritis. It has been studied in Phase 2 clinical trials for moderate to severe rheumatoid arthritis and ulcerative colitis, though it remains investigational and is not approved.
GSK2982772 is a small molecule that targets RIPK1, a kinase involved in necroptosis and inflammatory signaling. By inhibiting RIPK1, it aims to reduce inflammation and tissue damage in autoimmune and inflammatory conditions. This mechanism is being evaluated in clinical trials for diseases like rheumatoid arthritis and ulcerative colitis.
GSK2982772 is being developed by GSK plc, a global biopharma company listed on the NYSE under the ticker GSK. GSK has sponsored clinical trials of the drug in healthy volunteers and in patients with inflammatory and autoimmune conditions.
GSK2982772 has completed Phase 2 clinical trials for moderate to severe rheumatoid arthritis and ulcerative colitis. It has also completed Phase 1 trials in healthy subjects. The drug is investigational and not yet approved by regulatory authorities.
GSK2982772 has been studied in several completed trials. NCT02858492 was a Phase 2 study in rheumatoid arthritis, NCT02903966 was a Phase 2 study in ulcerative colitis, and NCT02302404 and NCT03305419 were Phase 1 studies in healthy subjects. All trials are completed.
GSK2982772 is the primary name used for this investigational drug in clinical trials and literature. No alternative names have been reported for this compound in the available data.