A Phase 1 interventional study of GSK2982772 Modified Release and GSK2982772 Immediate Release in Autoimmune Diseases, sponsored by GlaxoSmithKline. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-08-13.
Sponsored by GlaxoSmithKline · Phase 1, Interventional, and Treatment
GSK2982772 is a first-in-class, highly selective, receptor-interacting protein-1 (RIP1) kinase inhibitor being developed for the treatment of inflammatory bowel disease, plaque psoriasis (PsO), rheumatoid arthritis (RA) and other disease conditions. PK data from the first time in human (FTIH) study for GSK2982772 showed that the half life of GSK2982772 was short (approximately 2 to 3 hours). A once daily (QD) formulation would be more convenient from a subject perspective and could offer the advantage of providing a flatter GSK2982772 concentration time profile. Following completion of Parts A and B, it was determined that the slowest minitab formulation provided a PK profile suitable for QD dosing but this formulation was susceptible to a food effect. This study will evaluate the pharmacokinetics of GSK2982772 following administration of different minitab MR formulations in a capsule relative to an IR reference tablet formulation, the pharmacokinetics of selected MR formulation in capsule following repeat doses for 3 days and to compare the pharmacokinetics of GSK2982772 following administration of MR tablet formulations in the fed and fasted state relative to an IR tablet formulation. The study is divided into three parts: Part A will be a non-randomized 6 periods, sequential, 6-way fixed sequence design in which up to 4 MR minitab formulations in a capsule will be evaluated. Periods 1, 2, and 3 will evaluate a slow MR release duration (nominally 24 hours), a fast MR release duration (nominally 10 hours), and IR tablet respectively. Periods 4, 5 and 6 will have flexible dose regimen and it will depend on the outcomes of Period 1 to 3. Subjects will be admitted to the clinic the previous day before dosing. Each in-patient period will consist of 3 days and 2 nights followed by a minimum washout period of 7 days between doses, for both Part A and C. In Part A and C, 16 healthy subjects will be enrolled such that at least 12 evaluable subjects complete the study. Part B will be an open-label, repeat dose study in which the selected MR minitab formulation in capsule will be evaluated. Each in-patient period will consist of 5 days and 4 nights. There will be a minimum of 7 days washout period between the last morning dose of one period and the first dose of the next period. In Part B, 10 healthy subjects will be enrolled such that at least 6 evaluable subjects complete the study. Part C of the study will be a non-randomised 6 period, sequential, fixed sequence crossover design in which MR tablet formulations will be evaluated. Periods 1 and 2 will evaluate single dose administration of a 240 milligram (mg) MR tablet and the 240 mg IR tablet (reference), respectively. Periods 3, 4, 5 and 6 will be flexible and the dosing regimen will be dependent on the outcome of Periods 1 and 2.
Exclusion Criteria:
Subjects in Part A will receive GSK2982772 MR (Period 1, 2, 4, 5 and 6) and GSK2982772 IR (Period 3)
Drug: GSK2982772 Modified Release · Drug: GSK2982772 Immediate Release
Subjects in Part B will receive GSK2982772 MR
Drug: GSK2982772 Modified Release
Subjects in Part C will receive GSK2982772 MR (Period 1, 3, 4, 5 and 6) and GSK2982772 IR (Period 2)
Drug: GSK2982772 Modified Release · Drug: GSK2982772 Immediate Release
GSK2982772 MR will be available as prototype MR minitablet in capsules with unit dose strength of 60 mg in Part A. In Part B, GSK2982772 MR minitablet in capsules with unit dose strength of 15, 30 or 60 mg will be administered by subjects for Days 1 to 3. In Part C, GSK2982772 MR tablet with unit dose strength of 240, 360 or 480 mg will be administered by subjects. GSK2982772 MR will be administered orally with 240 mL of water.
In part A, GSK2982772 IR tablet will be available with unit dose strength of 30 mg and the total dose administered by subjects will be 120 mg (4 tablets of dose strength 30 mg) orally with 240 mL of water. In part C, GSK2982772 IR tablet will be available with unit dose strength of 30 mg and the total dose administered by subjects will be 240 mg (8 tablets of dose strength 30 mg) orally with 240 mL of water.
Area Under the Curve From Time Zero to Infinity (AUC[0-inf]) of GSK2982772 in IR Formulation: Part A
Blood samples were collected from participants at indicated time points and analyzed for AUC (0-inf). Participants in the 'Safety Population' for whom a Pharmacokinetic (PK) sample was obtained and analyzed were part of PK Population.
Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose
AUC(0-inf) of GSK2982772 in MT Formulation :Part A
Blood samples were collected from participants at indicated time points and analyzed for AUC (0-inf).
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose
Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of GSK2982772 in IR Formulation : Part A
Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t)
Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose
AUC(0-t) of GSK2982772 in MT Formulation: Part A
Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t)
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose
Area Under the Curve From Time Zero to 24 Hours (AUC[0-24]) of GSK2982772 in IR Formulation: Part A
Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24)
Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose
AUC(0-24) of GSK2982772 in MT Formulation: Part A
Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24)
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose
Area Under the Curve From Time Zero to 12 Hours (AUC[0-12]) of GSK2982772 in IR Formulation: Part A
Blood samples were collected from participants at indicated time points and analyzed for AUC (0-12)
Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours post-dose
AUC(0-12) of GSK2982772 in MT Formulation: Part A
Blood samples were collected from participants at indicated time points and analyzed for AUC (0-12)
Time frame: Pre-dose, 2, 4, 6, 8, 10, and 12 hours post-dose
Maximum Observed Concentration (Cmax) of GSK2982772 in IR Formulation: Part A
Blood samples were collected from participants at indicated time points and analyzed for Cmax
Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose
Cmax of GSK2982772 in MT Formulation: Part A
Blood samples were collected from participants at indicated time points and analyzed for Cmax
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose
Concentration at 12 Hours Post-dose (C12hour) of GSK2982772 in Part A
Blood samples were collected from participants at indicated time points and analyzed for C12hour.
Time frame: 12 hours post-dose
Concentration at 24 Hours Post-dose (C24hour) of GSK2982772 in Part A
Blood samples were collected from participants at indicated time points and analyzed for C24hour.
Time frame: 24 hours post-dose
Relative Bioavailability (Frelformulation) Based on AUC (0-inf) of GSK2982772 in Part A
Blood samples were collected at indicated time points for analysis of Frelformulation. Frelformulation for AUC (0-inf) was calculated as Geometric mean of AUC (0-inf) of MT (test) / Geometric mean of AUC (0-inf) of IR Formulation (reference) multiplied by 100.
Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose (reference); Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose (test)
Frelformulation Based on AUC (0-24) of GSK2982772 in Part A
Blood samples were collected at indicated time points for analysis of Frelformulation. Frelformulation for AUC (0-24) was calculated as Geometric mean of AUC (0-24) of MT (test) / Geometric mean of AUC (0-24) of IR Formulation (reference) multiplied by 100.
Time frame: Pre-dose 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose (reference); Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose (test)
Frelformulation Based on Cmax of GSK2982772 in Part A
Blood samples were collected at indicated time points for analysis of Frelformulation. Frel was calculated as Geometric mean of Cmax of MT Formulation (test)/ Geometric mean of Cmax of IR Formulation (reference) multiplied by 100.
Time frame: Pre-dose,0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose(reference); Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose(test)
Ratio of Cmax to C12hour of GSK2982772 in IR Formulation: Part A
Blood samples were collected at indicated time points for analysis of ratio of Cmax to C12hour. Mean and standard deviation of ratio of Cmax to C12 hour has been presented.
Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 26, 28, 30 and 32 hours post-dose
Ratio of Cmax to C12hour of GSK2982772 in MT Formulation: Part A
Blood samples were collected at indicated time points for analysis of ratio of Cmax to C12hour. Mean and standard deviation of ratio of Cmax to C12 hour has been presented.
Time frame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose
Ratio of Cmax to C24hour of GSK2982772 in IR Formulation: Part A
Blood samples were collected at indicated time points for analysis of ratio of Cmax to C24hour. Mean and standard deviation of ratio of Cmax to C24 hour has been presented.
Time frame: Pre-dose 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose
Ratio of Cmax to C24hour of GSK2982772 in MT Formulation: Part A
Blood samples were collected at indicated time points for analysis of ratio of Cmax to C24hour. Mean and standard deviation of ratio of Cmax to C24 hour has been presented.
Time frame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose
Time to Cmax (Tmax) of GSK2982772 in IR Formulation: Part A
Blood samples were collected at indicated time points for analysis of Tmax.
Time frame: Pre-dose 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose
Tmax of GSK2982772 in MT Formulation: Part A
Blood samples were collected at indicated time points for analysis of Tmax.
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose
AUC(0-inf) of GSK2982772 for IR Formulation in Part C: Fasted State
Blood samples were collected at indicated time points for analysis of AUC (0-inf)
Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
AUC(0-inf) of GSK2982772 for MM Formulation in Part C: Fasted State
Blood samples were collected at indicated time points for analysis of AUC (0-inf).
Time frame: Pre-dose, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
AUC(0-t) of GSK2982772 for IR Formulation in Part C: Fasted State
Blood samples were collected at indicated time points for analysis of AUC (0-t).
Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
AUC(0-t) of GSK2982772 for MM Formulation in Part C: Fasted State
Blood samples were collected at indicated time points for analysis of AUC (0-t).
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
AUC(0-24) of GSK2982772 for IR Formulation in Part C: Fasted State
Blood samples were collected at indicated time points for analysis of AUC (0-24)
Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
AUC(0-24) of GSK2982772 for MM Formulation in Part C: Fasted State
Blood samples were collected at indicated time points for analysis of AUC (0-24)
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours post-dose
AUC (0-12) of GSK2982772 for IR Formulation in Part C: Fasted State
Blood samples were collected at indicated time points for analysis of AUC (0-12)
Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose
AUC (0-12) of GSK2982772 for MM Formulation in Part C: Fasted State
Blood samples were collected at indicated time points for analysis of AUC (0-12)
Time frame: Pre-dose, 2, 4, 6, 8, 10, and 12 hours post-dose
Cmax of GSK2982772 for IR Formulation in Part C: Fasted State
Blood samples were collected at indicated time points for analysis of Cmax
Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
Cmax of GSK2982772 for MM Formulation in Part C: Fasted State
Blood samples were collected at indicated time points for analysis of Cmax
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
C12 of GSK2982772 in Part C: Fasted State
Blood samples was collected at indicated time point for analysis of C12
Time frame: 12 hours post-dose
C24 of GSK2982772 in Part C: Fasted State
Blood samples was collected at indicated time point for analysis of C24
Time frame: 24 hours post-dose
Ratio of Cmax to C12hour of GSK2982772 for IR Formulation in Part C: Fasted State
Blood samples were collected at indicated time points for analysis of ratio of Cmax to C12hour. Mean and standard deviation of ratio of Cmax to C12 hours has been presented.
Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
Ratio of Cmax to C12hour of GSK2982772 for MM Formulation in Part C: Fasted State
Blood samples were collected at indicated time points for analysis of ratio of Cmax to C12hour. Mean and standard deviation of ratio of Cmax to C12 hours has been presented.
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
Ratio of Cmax to C24hour of GSK2982772 for IR Formulation in Part C: Fasted State
Blood samples were collected at indicated time points for analysis of ratio of Cmax to C24hour. Mean and standard deviation of ratio of Cmax to C24 hours has been presented.
Time frame: Pre-dose,0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
Ratio of Cmax to C24hour of GSK2982772 for MM Formulation in Part C: Fasted State
Blood samples were collected at indicated time points for analysis of ratio of Cmax to C24hour. Mean and standard deviation of ratio of Cmax to C24 hours has been presented.
Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
Frelformulation Based on AUC (0-t) of GSK2982772 in Part C: Fasted State
Blood samples were collected at indicated time points for analysis of Frelformulation. Frel for AUC (0-t) was calculated as Geometric mean of AUC (0-t) of MM formulation (test) / Geometric mean of AUC (0-t) of IR Formulation (reference) multiplied by 100.
Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose(reference); Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose(test)
Frelformulation Based on AUC (0-24) of GSK2982772 in Part C: Fasted State
Blood samples were collected at indicated time points for analysis of Frelformulation. Frel for AUC (0-24) was calculated as Geometric mean of AUC (0-24) of MM Fasted formulation (test) / Geometric mean of AUC (0-24) of IR Formulation (reference) multiplied by 100.
Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose(reference); Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours post-dose(test)
Frelformulation Based on AUC (0-inf) of GSK2982772 After a High Fat Meal in Part A
Blood samples were collected at indicated time points for analysis of Frelformulation based on AUC of GSK2982772 after a high fat meal. Frel for AUC (0-inf) was calculated as Geometric mean of AUC (0-inf) of MT Fed formulation (test) / Geometric mean of AUC (0-inf) of MT Fasted Formulation (reference) multiplied by 100.
Time frame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose
Frelformulation Based on Cmax of GSK2982772 After a High Fat Meal in Part A
Blood samples were collected at indicated time points for analysis of FrelFE based on AUC of GSK2982772 after a high fat meal. Frel for Cmax was calculated as Geometric mean of Cmax of MT Fed formulation (test) / Geometric mean of Cmax of MT Fasted Formulation (reference) multiplied by 100.
Time frame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose
AUC(0-24) of GSK2982772 in Part B
Blood samples were collected at indicated time points for analysis of AUC (0-24)
Time frame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours on Day 1 and Day 3
Cmax of GSK2982772 in Part B
Blood samples were collected at indicated time points for analysis of Cmax
Time frame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours on Day 1 and Day 3
Tmax of GSK2982772 in Part B
Blood samples were collected at indicated time points for analysis of Tmax
Time frame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours on Day 1 and Day 3
AUC (0-24) of GSK2982772 After Meal in Part C
Blood samples were collected at indicated time points for analysis of AUC (0-24)
Time frame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours post-dose
Cmax of GSK2982772 After Meal in Part C
Blood samples were collected at indicated time points for analysis of Cmax
Time frame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours
C12 of GSK2982772 After Meal in Part C
Blood samples were collected at indicated time points for analysis of C12
Time frame: 12 hours post-dose
AUC(0-t) of GSK2982772 After Meal in Part C
Blood samples were collected at indicated time points for analysis of AUC (0-t)
Time frame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
AUC(0-inf) of GSK2982772 After Meal in Part C
Blood samples were collected at indicated time points for analysis of AUC (0-inf) after meal.
Time frame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
AUC(0-12) of GSK2982772 After Meal in Part C
Blood samples were collected at indicated time points for analysis of AUC (0-12) after meal.
Time frame: Pre-dose and at 2, 4, 6, 8, 10, and 12 hours post-dose
Frelformulation Based on AUC (0-t) of GSK2982772 After Meal in Part C
Blood samples were collected at indicated time points for analysis of Frelformulation based on AUC of GSK2982772 after meal. Frel for Auc (0-t) was calculated as Geometric mean of AUC (0-t) of MM Fed formulation (fed) / Geometric mean of AUC (0-t) of MM Fasted Formulation (fasted) multiplied by 100.
Time frame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
Frelformulation Based on Cmax of GSK2982772 After Meal in Part C
Blood samples were collected at indicated time points for analysis of Frelformulation based on Cmax of GSK2982772 after meal. Frel for Cmax was calculated as Geometric mean of Cmax of MM Fed formulation (test) / Geometric mean of Cmax of MM Fasted Formulation (reference) multiplied by 100.
Time frame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
Tmax of GSK2982772 After Meal in Part C
Blood samples were collected at indicated time points for analysis of Tmax of GSK2982772 after meal.
Time frame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
Number of Participants With Adverse Events (AE) and Serious AEs (SAE) in Part A
An AE is any untoward medical occurrence in a clinical study participants, 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 may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly or birth defect and important medical events may jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed before. All participants who receive at least 1 dose of study treatment and were included in Safety Population. Participants will be analyzed according to the treatment they actually received.
Time frame: Up to Day 43
Number of Participants With AE and SAE in Part B
An AE is any untoward medical occurrence in a clinical study participants, 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 may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly or birth defect and important medical events may jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed before.
Time frame: Up to Day 22
Number of Participants With AE and SAE in Part C
An AE is any untoward medical occurrence in a clinical study participants, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly or birth defect and important medical events may jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed before.
Time frame: Up to Day 43
Number of Participants With Emergent Clinical Chemistry Results by Potential Clinical Importance Criteria: Part A
Blood samples were collected for analysis of clinical chemistry parameters like albumin, creatinine, glucose, potassium, sodium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin and calcium. Participants are 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 are counted twice if the subject has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Participants with missing Baseline value are assumed to have normal baseline value. Clinical chemistry parameters with potential clinical importance data has been reported. Data for worst-case post-Baseline has been reported.
Time frame: Up to Day 43
Number of Participants With Emergent Hematology Results by Potential Clinical Importance Criteria: Part A
Blood samples were collected to analyze hematology parameters like platelet count, white blood cell (WBC) count, hemoglobin, hematocrit, total neutrophils, and lymphocytes. Participants are 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 are counted twice if the subject has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Participants with missing baseline value are assumed to have normal baseline value. Hematology parameters with potential clinical importance data has been reported. Data for worst-case post-Baseline has been reported.
Time frame: Up to Day 43
Number of Participants Abnormal Urinalysis Dipstick Results: Part A
Urine samples were collected for analysis of specific gravity, potential of hydrogen ions, glucose, protein, blood and ketones by dipstick method. Microscopic examination were performed if blood or protein values were abnormal.
Time frame: Up to Day 43
Number of Participants With Emergent Clinical Chemistry Results by Potential Clinical Importance Criteria: Part B
Blood samples were collected for analysis of clinical chemistry parameters like albumin, creatinine, glucose, potassium, sodium, AST, ALT, ALP, total bilirubin and calcium. Participants are 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 are counted twice if the subject has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Participants with missing baseline value are assumed to have normal baseline value. Hematology parameters with potential clinical importance data has been reported. Data for worst-case post-Baseline has been reported.
Time frame: Up to Day 22
Number of Participants With Emergent Hematology Results by Potential Clinical Importance Criteria: Part B
Blood samples were collected to analyze hematology parameters like platelet count, WBC count, hemoglobin, hematocrit, total neutrophils, and lymphocytes. Participants are 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 are counted twice if the subject has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Participants with missing baseline value are assumed to have normal baseline value. Hematology parameters with potential clinical importance data has been reported. Data for worst-case post-Baseline has been reported.
Time frame: Up to Day 22
Number of Participants Abnormal Urinalysis Dipstick Results: Part B
Urine samples were collected for analysis of specific gravity, potential of hydrogen ions, glucose, protein, blood and ketones by dipstick method. Microscopic examination were performed if blood or protein values were abnormal.
Time frame: Up to Day 22
Number of Participants With Emergent Clinical Chemistry Results by Potential Clinical Importance Criteria: Part C
Blood samples were collected for analysis of clinical chemistry parameters like albumin, creatinine, glucose, potassium, sodium, AST, ALT, ALP, total bilirubin and calcium. Participants are 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 are counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Participants with missing Baseline value are assumed to have normal Baseline value. Clinical chemistry parameters with potential clinical importance data has been reported. Data for worst-case post-Baseline has been reported.
Time frame: Up to Day 43
Number of Participants With Emergent Hematology Results by Potential Clinical Importance Criteria: Part C
Blood samples were collected to analyze hematology parameters like platelet count, WBC count, hemoglobin, hematocrit, total neutrophils, and lymphocytes. Participants are 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 are counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Participants with missing Baseline value are assumed to have normal Baseline value. Hematology parameters with potential clinical importance data has been reported. Data for worst-case post-Baseline has been reported.
Time frame: Up to Day 43
Number of Participants Abnormal Urinalysis Dipstick Results: Part C
Urine samples were collected for analysis of specific gravity, potential of hydrogen ions, glucose, protein, blood and ketones by dipstick method. Microscopic examination were performed if blood or protein values were abnormal.
Time frame: Up to Day 43
Number of Participants Abnormal Electrocardiogram (ECG) Findings: Part A
Single 12-lead ECGs was obtained using an ECG machine. PR, QRS, QT and Corrected QT (QTc) intervals were measured in semi-supine or supine position. Number of participants with any visit post-Baseline abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported. Data for worst-case post-Baseline has been reported.
Time frame: Up to Day 43
Number of Participants Abnormal ECG Findings: Part B
Single 12-lead ECGs was obtained using an ECG machine. PR, QRS, QT and QTc intervals were measured in semi-supine or supine position. Number of participants with any visit post-Baseline abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported. Data for worst-case post-Baseline has been reported.
Time frame: Up to Day 22
Number of Participants Abnormal ECG Findings: Part C
Single 12-lead ECGs was obtained using an ECG machine. PR, QRS, QT and QTc intervals were measured in semi-supine or supine position. Number of participants with any visit post-Baseline abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported. Data for worst-case post-Baseline has been reported.
Time frame: Up to Day 43
Change From Baseline in Blood Pressure: Part A
Systolic blood pressure (SBP) and diastolic blood pressure (DBP) was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours
Change From Baseline in Heart Rate: Part A
Heart rate was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1 Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours
Change From Baseline in Respiration Rate: Part A
Respiration rate was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value
Time frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours
Change From Baseline in Body Temperature: Part A
Body temperature was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours
Change From Baseline in Blood Pressure: Part B
SBP and DBP was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Day 1 and Day 3: 2 and 12 hours; Pre-dose on Days 2 and 3; Day 4: 24 hours
Change From Baseline in Heart Rate: Part B
Heart rate was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Day 1 and Day 3: 2 and 12 hours; Pre-dose on Days 2 and 3; Day 4: 24 hours
Change From Baseline in Respiration Rate: Part B
Respiration rate was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value
Time frame: Baseline (Day 1, Pre-dose), Day 1 and Day 3: 2 and 12 hours; Pre-dose on Days 2 and 3; Day 4 24 hours
Change From Baseline in Body Temperature: Part B
Body temperature was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Day 1 and Day 3: 2 and 12 hours; Pre-dose on Days 2 and 3; Day 4: 24 hours
Change From Baseline in Blood Pressure: Part C
SBP and DBP was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours
Change From Baseline in Heart Rate: Part C
Heart rate was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours
Change From Baseline in Respiration Rate: Part C
Respiration rate was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours
Change From Baseline in Body Temperature: Part C
Body temperature was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours
This was an open label, 3-part, single and repeat dose study conducted in healthy participants to assess modified release (MR) minitablets (MT) in a capsule and MR monolithic matrix (MM) formulations of GSK2982772 compared to immediate release (IR) tablet formulation of GSK2982772.
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 16 | 0 | 0 |
| Completed | 15 | 0 | 0 |
| Not completed | 1 | 0 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 15 | 0 | 0 |
| Completed | 13 | 0 | 0 |
| Not completed | 2 | 0 | 0 |
| Withdrew: Adverse event | 1 | 0 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 13 | 0 | 0 |
| Completed | 13 | 0 | 0 |
| Not completed | 0 | 0 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 13 | 0 | 0 |
| Completed | 13 | 0 | 0 |
| Not completed | 0 | 0 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 16 | 0 | 0 |
| Completed | 16 | 0 | 0 |
| Not completed | 0 | 0 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 16 | 0 | 0 |
| Completed | 16 | 0 | 0 |
| Not completed | 0 | 0 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 16 | 0 | 0 |
| Completed | 16 | 0 | 0 |
| Not completed | 0 | 0 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 0 | 10 | 0 |
| Completed | 0 | 10 | 0 |
| Not completed | 0 | 0 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 0 | 10 | 0 |
| Completed | 0 | 10 | 0 |
| Not completed | 0 | 0 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 0 | 10 | 0 |
| Completed | 0 | 10 | 0 |
| Not completed | 0 | 0 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 0 | 10 | 0 |
| Completed | 0 | 8 | 0 |
| Not completed | 0 | 2 | 0 |
| Withdrew: Withdrawal by subject | 0 | 2 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 0 | 6 | 0 |
| Completed | 0 | 6 | 0 |
| Not completed | 0 | 0 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 0 | 0 | 15 |
| Completed | 0 | 0 | 15 |
| Not completed | 0 | 0 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 0 | 0 | 15 |
| Completed | 0 | 0 | 15 |
| Not completed | 0 | 0 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 0 | 0 | 15 |
| Completed | 0 | 0 | 15 |
| Not completed | 0 | 0 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 0 | 0 | 15 |
| Completed | 0 | 0 | 15 |
| Not completed | 0 | 0 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 0 | 0 | 16 |
| Completed | 0 | 0 | 16 |
| Not completed | 0 | 0 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 0 | 0 | 16 |
| Completed | 0 | 0 | 16 |
| Not completed | 0 | 0 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 0 | 0 | 16 |
| Completed | 0 | 0 | 16 |
| Not completed | 0 | 0 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 0 | 0 | 16 |
| Completed | 0 | 0 | 15 |
| Not completed | 0 | 0 | 1 |
| Withdrew: Withdrawal by subject | 0 | 0 | 1 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 0 | 0 | 15 |
| Completed | 0 | 0 | 15 |
| Not completed | 0 | 0 | 0 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 0 | 0 | 15 |
| Completed | 0 | 0 | 14 |
| Not completed | 0 | 0 | 1 |
| Withdrew: Withdrawal by subject | 0 | 0 | 1 |
| Milestone | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF |
|---|---|---|---|
| Started | 0 | 0 | 14 |
| Completed | 0 | 0 | 14 |
| Not completed | 0 | 0 | 0 |
Blood samples were collected from participants at indicated time points and analyzed for AUC (0-inf). Participants in the 'Safety Population' for whom a Pharmacokinetic (PK) sample was obtained and analyzed were part of PK Population.
| Hours*microgram per milliliter | Part A: IR 120mg Fasted |
|---|---|
| Area Under the Curve From Time Zero to Infinity (AUC[0-inf]) of GSK2982772 in IR Formulation: Part A | 6.305 ± 39.4 |
Blood samples were collected from participants at indicated time points and analyzed for AUC (0-inf).
| Hours*microgram per milliliter | Part A: MT-12hour 120mg Fasted | Part A: MT-8hour 120mg Fasted | Part A: MT-12hour 120mg Fed (High Fat) |
|---|---|---|---|
| AUC(0-inf) of GSK2982772 in MT Formulation :Part A | 3.852 ± 39.4 | 4.482 ± 47.4 | 5.314 ± 39.7 |
Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t)
| Hours*microgram per milliliter | Part A: IR 120mg Fasted |
|---|---|
| Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of GSK2982772 in IR Formulation : Part A | 6.258 ± 39.2 |
Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t)
| Hours*microgram per milliliter | Part A: MT-12hour 120mg Fasted | Part A:MT-8hour 120mg Fasted | Part A: MT-12hour 120mg Fed (High Fat) |
|---|---|---|---|
| AUC(0-t) of GSK2982772 in MT Formulation: Part A | 3.805 ± 42.3 | 4.449 ± 49.4 | 4.720 ± 38.4 |
Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24)
| Hours*microgram per milliliter | Part A: IR 120mg Fasted |
|---|---|
| Area Under the Curve From Time Zero to 24 Hours (AUC[0-24]) of GSK2982772 in IR Formulation: Part A | 6.256 ± 39.2 |
Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24)
| Hours*microgram per milliliter | Part A:MT-12hour 120mg Fasted | Part A: MT-8hour 120mg Fasted | Part A: MT-12hour 120mg Fed (High Fat) |
|---|---|---|---|
| AUC(0-24) of GSK2982772 in MT Formulation: Part A | 3.558 ± 43.6 | 4.255 ± 49.4 | 4.580 ± 39.5 |
Blood samples were collected from participants at indicated time points and analyzed for AUC (0-12)
| Hours*microgram per milliliter | Part A: IR 120mg Fasted |
|---|---|
| Area Under the Curve From Time Zero to 12 Hours (AUC[0-12]) of GSK2982772 in IR Formulation: Part A | 5.967 ± 38.4 |
Blood samples were collected from participants at indicated time points and analyzed for AUC (0-12)
| Hours*microgram per milliliter | Part A:MT-12hour 120mg Fasted | Part A:MT-8hour 120mg Fasted | Part A: MT-12hour 120mg Fed (High Fat) |
|---|---|---|---|
| AUC(0-12) of GSK2982772 in MT Formulation: Part A | 2.106 ± 45.1 | 3.066 ± 47.7 | 3.573 ± 40.8 |
Blood samples were collected from participants at indicated time points and analyzed for Cmax
| Microgram per milliliter | Part A: IR 120mg Fasted |
|---|---|
| Maximum Observed Concentration (Cmax) of GSK2982772 in IR Formulation: Part A | 1.375 ± 40.1 |
Blood samples were collected from participants at indicated time points and analyzed for Cmax
| Microgram per milliliter | Part A: MT-12hour 120mg Fasted | Part A: MT-8hour 120mg Fasted | Part A: MT-12hour 120mg Fed (High Fat) |
|---|---|---|---|
| Cmax of GSK2982772 in MT Formulation: Part A | 0.277 ± 58.8 | 0.439 ± 54.9 | 0.624 ± 49.4 |
Blood samples were collected from participants at indicated time points and analyzed for C12hour.
| Microgram per milliliter | Part A: MT-12hour 120mg Fasted | Part A: MT-8hour 120mg Fasted | Part A: MT-12hour 120mg Fed (High Fat) | Part A: IR 120mg Fasted |
|---|---|---|---|---|
| Concentration at 12 Hours Post-dose (C12hour) of GSK2982772 in Part A | 0.220 ± 52.6 | 0.209 ± 56.2 | 0.208 ± 53.1 | 0.045 ± 81.7 |
Blood samples were collected from participants at indicated time points and analyzed for C24hour.
| Microgram per milliliter | Part A: MT-12hour 120mg Fasted | Part A: MT-8hour 120mg Fasted | Part A: MT-12hour 120mg Fed (High Fat) | Part A: IR 120mg Fasted |
|---|---|---|---|---|
| Concentration at 24 Hours Post-dose (C24hour) of GSK2982772 in Part A | 0.058 ± 73.2 | 0.046 ± 69.5 | 0.030 ± 46.6 | 0.006 ± 108.8 |
Blood samples were collected at indicated time points for analysis of Frelformulation. Frelformulation for AUC (0-inf) was calculated as Geometric mean of AUC (0-inf) of MT (test) / Geometric mean of AUC (0-inf) of IR Formulation (reference) multiplied by 100.
| Percentage bioavailability | Part A:120 mg MT-8hr Fasted and 120 mg IR Fasted | Part A:120 mg MT-12hr Fasted and 120 mg IR Fasted |
|---|---|---|
| Relative Bioavailability (Frelformulation) Based on AUC (0-inf) of GSK2982772 in Part A | 72.77 (67.91 to 77.98) | 60.53 (56.15 to 65.24) |
Blood samples were collected at indicated time points for analysis of Frelformulation. Frelformulation for AUC (0-24) was calculated as Geometric mean of AUC (0-24) of MT (test) / Geometric mean of AUC (0-24) of IR Formulation (reference) multiplied by 100.
| Percentage bioavailability | Part A:120 mg MT-8hr Fasted and 120 mg IR Fasted | Part A:120 mg MT-12hr Fasted and 120 mg IR Fasted |
|---|---|---|
| Frelformulation Based on AUC (0-24) of GSK2982772 in Part A | 68.18 (63.98 to 72.64) | 57.54 (54.01 to 61.30) |
Blood samples were collected at indicated time points for analysis of Frelformulation. Frel was calculated as Geometric mean of Cmax of MT Formulation (test)/ Geometric mean of Cmax of IR Formulation (reference) multiplied by 100.
| Percentage bioavailability | Part A:120 mg MT-8hr Fasted and 120 mg IR Fasted | Part A:120 mg MT-12hr Fasted and 120 mg IR Fasted |
|---|---|---|
| Frelformulation Based on Cmax of GSK2982772 in Part A | 32.13 (27.36 to 37.75) | 20.39 (17.41 to 23.89) |
Blood samples were collected at indicated time points for analysis of ratio of Cmax to C12hour. Mean and standard deviation of ratio of Cmax to C12 hour has been presented.
| Ratio | Part A: IR 120mg Fasted |
|---|---|
| Ratio of Cmax to C12hour of GSK2982772 in IR Formulation: Part A | 36.485 ± 20.9265 |
Blood samples were collected at indicated time points for analysis of ratio of Cmax to C12hour. Mean and standard deviation of ratio of Cmax to C12 hour has been presented.
| Ratio | Part A: MT-12hour 120mg Fasted | Part A: MT-8hour 120mg Fasted | Part A: MT-12hour 120mg Fed (High Fat) |
|---|---|---|---|
| Ratio of Cmax to C12hour of GSK2982772 in MT Formulation: Part A | 1.284 ± 0.2468 | 2.265 ± 0.9119 | 3.240 ± 1.2250 |
Blood samples were collected at indicated time points for analysis of ratio of Cmax to C24hour. Mean and standard deviation of ratio of Cmax to C24 hour has been presented.
| Ratio | Part A: IR 120mg Fasted |
|---|---|
| Ratio of Cmax to C24hour of GSK2982772 in IR Formulation: Part A | 312.851 ± 221.7640 |
Blood samples were collected at indicated time points for analysis of ratio of Cmax to C24hour. Mean and standard deviation of ratio of Cmax to C24 hour has been presented.
| Ratio | Part A: MT-12hour 120mg Fasted | Part A: MT-8hour 120mg Fasted | Part A: MT-12hour 120mg Fed (High Fat) |
|---|---|---|---|
| Ratio of Cmax to C24hour of GSK2982772 in MT Formulation: Part A | 6.119 ± 5.1507 | 10.790 ± 4.9019 | 22.915 ± 11.7978 |
Blood samples were collected at indicated time points for analysis of Tmax.
| Hours | Part A: IR 120mg Fasted |
|---|---|
| Time to Cmax (Tmax) of GSK2982772 in IR Formulation: Part A | 2.000 (0.67 to 3.00) |
Blood samples were collected at indicated time points for analysis of Tmax.
| Hours | Part A: MT-12hour 120mg Fasted | Part A: MT-8hour 120mg Fasted | Part A: MT-12hour 120mg Fed (High Fat) |
|---|---|---|---|
| Tmax of GSK2982772 in MT Formulation: Part A | 10.000 (2.08 to 18.00) | 4.000 (4.00 to 10.00) | 6.000 (4.00 to 10.00) |
Blood samples were collected at indicated time points for analysis of AUC (0-inf)
| Hours*microgram per milliliter | Part C: IR 240mg Fasted |
|---|---|
| AUC(0-inf) of GSK2982772 for IR Formulation in Part C: Fasted State | 14.797 ± 26.3 |
Blood samples were collected at indicated time points for analysis of AUC (0-inf).
| Hours*microgram per milliliter | Part C: MM-12h 240mg Fasted | Part C: MM-12h 480mg Fasted |
|---|---|---|
| AUC(0-inf) of GSK2982772 for MM Formulation in Part C: Fasted State | 13.417 ± 23.4 | 22.493 ± 51.3 |
Blood samples were collected at indicated time points for analysis of AUC (0-t).
| Hours*microgram per milliliter | Part C: IR 240mg Fasted |
|---|---|
| AUC(0-t) of GSK2982772 for IR Formulation in Part C: Fasted State | 14.621 ± 25.7 |
Blood samples were collected at indicated time points for analysis of AUC (0-t).
| Hours*microgram per milliliter | Part C: MM-12h 240mg Fasted | Part C: MM-12h 480mg Fasted |
|---|---|---|
| AUC(0-t) of GSK2982772 for MM Formulation in Part C: Fasted State | 9.676 ± 29.6 | 20.009 ± 29.7 |
Blood samples were collected at indicated time points for analysis of AUC (0-24)
| Hours*microgram per milliliter | Part C: IR 240mg Fasted |
|---|---|
| AUC(0-24) of GSK2982772 for IR Formulation in Part C: Fasted State | 14.619 ± 25.7 |
Blood samples were collected at indicated time points for analysis of AUC (0-24)
| Hours*microgram per milliliter | Part C: MM-12h 240mg Fasted | Part C: MM-12h 480mg Fasted |
|---|---|---|
| AUC(0-24) of GSK2982772 for MM Formulation in Part C: Fasted State | 8.769 ± 30.9 | 18.177 ± 31.5 |
Blood samples were collected at indicated time points for analysis of AUC (0-12)
| Hours*microgram per milliliter | Part C: IR 240mg Fasted |
|---|---|
| AUC (0-12) of GSK2982772 for IR Formulation in Part C: Fasted State | 13.500 ± 26.3 |
Blood samples were collected at indicated time points for analysis of AUC (0-12)
| Hours*microgram per milliliter | Part C: MM-12h 240mg Fasted | Part C: MM-12h 480mg Fasted |
|---|---|---|
| AUC (0-12) of GSK2982772 for MM Formulation in Part C: Fasted State | 6.096 ± 32.8 | 12.508 ± 40.1 |
Blood samples were collected at indicated time points for analysis of Cmax
| Microgram per milliliter | Part C: IR 240mg Fasted |
|---|---|
| Cmax of GSK2982772 for IR Formulation in Part C: Fasted State | 2.938 ± 25.2 |
Blood samples were collected at indicated time points for analysis of Cmax
| Microgram per milliliter | Part C: MM-12h 240mg Fasted | Part C: MM-12h 480mg Fasted |
|---|---|---|
| Cmax of GSK2982772 for MM Formulation in Part C: Fasted State | 0.918 ± 34.2 | 2.010 ± 50.1 |
Blood samples was collected at indicated time point for analysis of C12
| Microgram per milliliter | Part C: IR 240mg Fasted | Part C: MM-12h 240mg Fasted | Part C: MM-12h 480mg Fasted |
|---|---|---|---|
| C12 of GSK2982772 in Part C: Fasted State | 0.197 ± 62.9 | 0.346 ± 41.7 | 0.671 ± 42.3 |
Blood samples was collected at indicated time point for analysis of C24
| Microgram per milliliter | Part C: IR 240mg Fasted | Part C: MM-12h 240mg Fasted | Part C: MM-12h 480mg Fasted |
|---|---|---|---|
| C24 of GSK2982772 in Part C: Fasted State | 0.025 ± 54.9 | 0.162 ± 52.6 | 0.351 ± 52.5 |
Blood samples were collected at indicated time points for analysis of ratio of Cmax to C12hour. Mean and standard deviation of ratio of Cmax to C12 hours has been presented.
| Ratio | Part C: IR 240mg Fasted |
|---|---|
| Ratio of Cmax to C12hour of GSK2982772 for IR Formulation in Part C: Fasted State | 17.158 ± 7.9158 |
Blood samples were collected at indicated time points for analysis of ratio of Cmax to C12hour. Mean and standard deviation of ratio of Cmax to C12 hours has been presented.
| Ratio | Part C: MM-12h 240mg Fasted | Part C: MM-12h 480mg Fasted |
|---|---|---|
| Ratio of Cmax to C12hour of GSK2982772 for MM Formulation in Part C: Fasted State | 2.892 ± 1.2572 | 3.551 ± 2.2615 |
Blood samples were collected at indicated time points for analysis of ratio of Cmax to C24hour. Mean and standard deviation of ratio of Cmax to C24 hours has been presented.
| Ratio | Part C: IR 240mg Fasted |
|---|---|
| Ratio of Cmax to C24hour of GSK2982772 for IR Formulation in Part C: Fasted State | 138.239 ± 76.3996 |
Blood samples were collected at indicated time points for analysis of ratio of Cmax to C24hour. Mean and standard deviation of ratio of Cmax to C24 hours has been presented.
| Ratio | Part C: MM-12h 240mg Fasted | Part C: MM-12h 480mg Fasted |
|---|---|---|
| Ratio of Cmax to C24hour of GSK2982772 for MM Formulation in Part C: Fasted State | 6.026 ± 2.1936 | 7.991 ± 10.6319 |
Blood samples were collected at indicated time points for analysis of Frelformulation. Frel for AUC (0-t) was calculated as Geometric mean of AUC (0-t) of MM formulation (test) / Geometric mean of AUC (0-t) of IR Formulation (reference) multiplied by 100.
| Percentage bioavailability | Part C:MM-12h 240mg Fasted and IR 240mg Fasted |
|---|---|
| Frelformulation Based on AUC (0-t) of GSK2982772 in Part C: Fasted State | 66.18 (61.91 to 70.74) |
Blood samples were collected at indicated time points for analysis of Frelformulation. Frel for AUC (0-24) was calculated as Geometric mean of AUC (0-24) of MM Fasted formulation (test) / Geometric mean of AUC (0-24) of IR Formulation (reference) multiplied by 100.
| Percentage bioavailability | Part C:MM-12h 240mg Fasted and IR 240mg Fasted |
|---|---|
| Frelformulation Based on AUC (0-24) of GSK2982772 in Part C: Fasted State | 59.98 (55.06 to 65.34) |
Blood samples were collected at indicated time points for analysis of Frelformulation based on AUC of GSK2982772 after a high fat meal. Frel for AUC (0-inf) was calculated as Geometric mean of AUC (0-inf) of MT Fed formulation (test) / Geometric mean of AUC (0-inf) of MT Fasted Formulation (reference) multiplied by 100.
| Percentage bioavailability | Part A:120 mg MT-12hour Fed and 120 mg MT-12hour Fasted |
|---|---|
| Frelformulation Based on AUC (0-inf) of GSK2982772 After a High Fat Meal in Part A | 123.64 (115.98 to 131.80) |
Blood samples were collected at indicated time points for analysis of FrelFE based on AUC of GSK2982772 after a high fat meal. Frel for Cmax was calculated as Geometric mean of Cmax of MT Fed formulation (test) / Geometric mean of Cmax of MT Fasted Formulation (reference) multiplied by 100.
| Percentage bioavailability | Part A:120 mg MT-12hour Fed and 120 mg MT-12hour Fasted |
|---|---|
| Frelformulation Based on Cmax of GSK2982772 After a High Fat Meal in Part A | 225.07 (201.78 to 251.04) |
Blood samples were collected at indicated time points for analysis of AUC (0-24)
| Hours*microgram/milliliter | Part B: MT-12 120mg Fasted | Part B :MT-12 240mg Fasted | Part B :MT-12hour 300mg Fed (Standard) |
|---|---|---|---|
| Day 1, n=10, 9, 5 | 4.669 ± 26.5 | 8.807 ± 34.3 | 9.662 ± 33.8 |
| Day 3, n=10, 10, 6 | 5.010 ± 32.0 | 9.867 ± 30.4 | 10.948 ± 37.7 |
Blood samples were collected at indicated time points for analysis of Cmax
| Microgram/milliliter | Part B: MT-12 120mg Fasted | Part B :MT-12 240mg Fasted | Part B :MT-12hour 300mg Fed (Standard) |
|---|---|---|---|
| Day 1 | 0.417 ± 25.5 | 0.707 ± 44.7 | 0.888 ± 14.1 |
| Day 3 | 0.398 ± 32.9 | 0.794 ± 35.7 | 1.080 ± 40.4 |
Blood samples were collected at indicated time points for analysis of Tmax
| Hours | Part B: MT-12 120mg Fasted | Part B :MT-12 240mg Fasted | Part B :MT-12hour 300mg Fed (Standard) |
|---|---|---|---|
| Day 1 | 4.058 (4.00 to 10.00) | 4.067 (4.00 to 12.00) | 4.000 (4.00 to 10.00) |
| Day 3 | 4.000 (2.00 to 16.0) | 5.025 (4.00 to 20.00) | 4.000 (4.00 to 6.00) |
Blood samples were collected at indicated time points for analysis of AUC (0-24)
| Hours*microgram/milliliter | Part C MM-12h 480mg Delayed Fed (Standard) | Part C MM-12h 240mg Delayed Fed (High Fat) | Part C MM-12h 480mg Fed (Standard) |
|---|---|---|---|
| AUC (0-24) of GSK2982772 After Meal in Part C | 17.505 ± 29.5 | 8.734 ± 47.4 | 21.543 ± 39.2 |
Blood samples were collected at indicated time points for analysis of Cmax
| Microgram/milliliter | Part C MM-12h 480mg Delayed Fed (Standard) | Part C MM-12h 240mg Delayed Fed (High Fat) | Part C MM-12h 480mg Fed (Standard) |
|---|---|---|---|
| Cmax of GSK2982772 After Meal in Part C | 1.547 ± 40.8 | 1.064 ± 62.6 | 3.151 ± 32.5 |
Blood samples were collected at indicated time points for analysis of C12
| Microgram/milliliter | Part C MM-12h 480mg Delayed Fed (Standard) | Part C MM-12h 240mg Delayed Fed (High Fat) | Part C MM-12h 480mg Fed (Standard) |
|---|---|---|---|
| C12 of GSK2982772 After Meal in Part C | 0.706 ± 72.7 | 0.739 ± 37.1 | 0.317 ± 49.5 |
Blood samples were collected at indicated time points for analysis of AUC (0-t)
| Hours*microgram/milliliter | Part C MM-12h 480mg Delayed Fed (Standard) | Part C MM-12h 240mg Delayed Fed (High Fat) | Part C MM-12h 480mg Fed (Standard) |
|---|---|---|---|
| AUC(0-t) of GSK2982772 After Meal in Part C | 19.147 ± 28.0 | 9.202 ± 46.4 | 22.712 ± 36.2 |
Blood samples were collected at indicated time points for analysis of AUC (0-inf) after meal.
| Hours*microgram/milliliter | Part C MM-12h 480mg Delayed Fed (Standard) | Part C MM-12h 240mg Delayed Fed (High Fat) | Part C MM-12h 480mg Fed (Standard) |
|---|---|---|---|
| AUC(0-inf) of GSK2982772 After Meal in Part C | 18.941 ± 36.5 | 9.995 ± 62.4 | 24.367 ± 49.2 |
Blood samples were collected at indicated time points for analysis of AUC (0-12) after meal.
| Hours*microgram/milliliter | Part C MM-12h 480mg Delayed Fed (Standard) | Part C MM-12h 240mg Delayed Fed (High Fat) | Part C MM-12h 480mg Fed (Standard) |
|---|---|---|---|
| AUC(0-12) of GSK2982772 After Meal in Part C | 17.111 ± 45.0 | 10.241 ± 45.9 | 6.771 ± 56.7 |
Blood samples were collected at indicated time points for analysis of Frelformulation based on AUC of GSK2982772 after meal. Frel for Auc (0-t) was calculated as Geometric mean of AUC (0-t) of MM Fed formulation (fed) / Geometric mean of AUC (0-t) of MM Fasted Formulation (fasted) multiplied by 100.
| Percentage bioavailability | Part C:480mg MM-12hour Delayed Fed and 480 mg MM-12hour Fasted | Part C:480mg MM-12hour Fed and 480 mg MM- 12hour Fasted | Part C:240mg MM-12hour Delayed Fed and 240mg MM-12hour Fasted |
|---|---|---|---|
| Frelformulation Based on AUC (0-t) of GSK2982772 After Meal in Part C | 94.69 (87.03 to 103.04) | 113.51 (104.52 to 123.27) | 91.13 (82.23 to 100.98) |
Blood samples were collected at indicated time points for analysis of Frelformulation based on Cmax of GSK2982772 after meal. Frel for Cmax was calculated as Geometric mean of Cmax of MM Fed formulation (test) / Geometric mean of Cmax of MM Fasted Formulation (reference) multiplied by 100.
| Percentage bioavailability | Part C:480mg MM-12hour Delayed Fed and 480 mg MM-12hour Fasted | Part C:480mg MM-12hour Fed and 480 mg MM- 12hour Fasted | Part C:240mg MM-12hour Delayed Fed and 240mg MM-12hour Fasted |
|---|---|---|---|
| Frelformulation Based on Cmax of GSK2982772 After Meal in Part C | 76.56 (64.25 to 91.22) | 156.77 (132.06 to 186.09) | 113.81 (94.00 to 137.78) |
Blood samples were collected at indicated time points for analysis of Tmax of GSK2982772 after meal.
| Hours | Part C MM-12h 480mg Delayed Fed (Standard) | Part C MM-12h 240mg Delayed Fed (High Fat) | Part C MM-12h 480mg Fed (Standard) |
|---|---|---|---|
| Tmax of GSK2982772 After Meal in Part C | 4.000 (2.00 to 20.00) | 4.000 (2.00 to 10.02) | 5.017 (4.00 to 10.00) |
An AE is any untoward medical occurrence in a clinical study participants, 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 may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly or birth defect and important medical events may jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed before. All participants who receive at least 1 dose of study treatment and were included in Safety Population. Participants will be analyzed according to the treatment they actually received.
| Participants | Part A: IR 120mg Fasted | Part A: MT-12hour 120mg Fasted | Part A: MT-8hour 120mg Fasted | Part A: MT-12hour 120mg Fed (High Fat) |
|---|---|---|---|---|
| Any AEs | 4 | 5 | 1 | 2 |
| Any SAEs | 0 | 1 | 0 | 0 |
An AE is any untoward medical occurrence in a clinical study participants, 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 may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly or birth defect and important medical events may jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed before.
| Participants | Part B: MT-12 120mg Fasted | Part B :MT-12 240mg Fasted | Part B :MT-12hour 300mg Fed (Standard) |
|---|---|---|---|
| Any AEs | 1 | 3 | 1 |
| Any SAEs | 0 | 0 | 0 |
An AE is any untoward medical occurrence in a clinical study participants, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly or birth defect and important medical events may jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed before.
| Participants | Part C: IR 240mg Fasted | Part C:MM-12h 240mg Fasted | Part C:MM-12h 480mg Fasted | Part C:MM-12h 480mg Fed(Standard) | Part C:MM-12h 480mg Delayed Fed(Standard) | Part C: MM-12h 240mg Delayed Fed(High Fat) |
|---|---|---|---|---|---|---|
| Any AEs | 3 | 3 | 3 | 4 | 2 | 1 |
| Any SAEs | 0 | 0 | 0 | 0 | 0 | 0 |
Blood samples were collected for analysis of clinical chemistry parameters like albumin, creatinine, glucose, potassium, sodium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin and calcium. Participants are 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 are counted twice if the subject has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Participants with missing Baseline value are assumed to have normal baseline value. Clinical chemistry parameters with potential clinical importance data has been reported. Data for worst-case post-Baseline has been reported.
| Participants | Part A: MT-12hour 120mg Fasted | Part A: MT-8hour 120mg Fasted | Part A: MT-12hour 120mg Fed (High Fat) | Part A: IR 120mg Fasted |
|---|---|---|---|---|
| ALT, low | 0 | 0 | 0 | 0 |
| ALT, normal or no change | 16 | 13 | 16 | 16 |
| ALT, high | 0 | 0 | 0 | 0 |
| Albumin, low | 0 | 0 | 0 | 0 |
| Albumin, normal or no change | 16 | 13 | 16 | 16 |
| Albumin, high | 0 | 0 | 0 | 0 |
| ALP, low | 0 | 0 | 0 | 0 |
| ALP, normal or no change | 16 | 13 | 16 | 16 |
| ALP, high | 0 | 0 | 0 | 0 |
| AST, low | 0 | 0 | 0 | 0 |
| AST, normal or no change | 16 | 13 | 16 | 16 |
| AST, high | 0 | 0 | 0 | 0 |
| Calcium, low | 0 | 0 | 0 | 0 |
| Calcium, normal or no change | 16 | 13 | 16 | 16 |
| Calcium, high | 0 | 0 | 0 | 0 |
| Creatinine, low | 0 | 0 | 0 | 0 |
| Creatinine, normal or no change | 16 | 13 | 16 | 16 |
| Creatinine, high | 0 | 0 | 0 | 0 |
| Glucose, low | 0 | 0 | 0 | 0 |
| Glucose, normal or no change | 16 | 13 | 16 | 16 |
| Glucose, high | 0 | 0 | 0 | 0 |
| Potassium, low | 0 | 0 | 0 | 0 |
| Potassium, normal or no change | 15 | 13 | 16 | 15 |
| Potassium, high | 1 | 0 | 0 | 1 |
| Sodium, low | 0 | 0 | 0 | 0 |
| Sodium, normal or no change16 | 16 | 13 | 16 | 16 |
| Sodium, high | 0 | 0 | 0 | 0 |
| Total Bilirubin, low | 0 | 0 | 0 | 0 |
| Total Bilirubin, normal or no change | 16 | 13 | 16 | 16 |
| Total Bilirubin, high | 0 | 0 | 0 | 0 |
Blood samples were collected to analyze hematology parameters like platelet count, white blood cell (WBC) count, hemoglobin, hematocrit, total neutrophils, and lymphocytes. Participants are 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 are counted twice if the subject has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Participants with missing baseline value are assumed to have normal baseline value. Hematology parameters with potential clinical importance data has been reported. Data for worst-case post-Baseline has been reported.
| Participants | Part A: MT-12hour 120mg Fasted | Part A: MT-8hour 120mg Fasted | Part A: MT-12hour 120mg Fed (High Fat) | Part A: IR 120mg Fasted |
|---|---|---|---|---|
| Hematocrit, low | 0 | 0 | 0 | 0 |
| Hematocrit, normal or no change | 16 | 13 | 16 | 16 |
| Hematocrit, high | 0 | 0 | 0 | 0 |
| Hemoglobin, low | 0 | 0 | 0 | 0 |
| Hemoglobin, normal or no change | 16 | 13 | 16 | 16 |
| Hemoglobin, high | 0 | 0 | 0 | 0 |
| Lymphocytes, low | 0 | 0 | 0 | 0 |
| Lymphocytes, normal or no change | 16 | 13 | 16 | 16 |
| Lymphocytes, high | 0 | 0 | 0 | 0 |
| Platelet count, low | 0 | 0 | 0 | 0 |
| Platelet count, normal or no change | 16 | 13 | 16 | 16 |
| Platelet count, high | 0 | 0 | 0 | 0 |
| Total Neutrophils, low | 1 | 2 | 0 | 0 |
| Total Neutrophils, normal or no change | 15 | 11 | 16 | 16 |
| Total Neutrophils, high | 0 | 0 | 0 | 0 |
| WBC, low | 1 | 1 | 0 | 0 |
| WBC, normal or no change | 15 | 12 | 16 | 16 |
| WBC, high | 0 | 0 | 0 | 0 |
Urine samples were collected for analysis of specific gravity, potential of hydrogen ions, glucose, protein, blood and ketones by dipstick method. Microscopic examination were performed if blood or protein values were abnormal.
| Participants | Part A: MT-12hour 120mg Fasted | Part A: MT-8hour 120mg Fasted | Part A: MT-12hour 120mg Fed (High Fat) | Part A: IR 120mg Fasted |
|---|---|---|---|---|
| Number of Participants Abnormal Urinalysis Dipstick Results: Part A | 0 | 0 | 0 | 0 |
Blood samples were collected for analysis of clinical chemistry parameters like albumin, creatinine, glucose, potassium, sodium, AST, ALT, ALP, total bilirubin and calcium. Participants are 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 are counted twice if the subject has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Participants with missing baseline value are assumed to have normal baseline value. Hematology parameters with potential clinical importance data has been reported. Data for worst-case post-Baseline has been reported.
| Participants | Part B: MT-12 120mg Fasted | Part B :MT-12 240mg Fasted | Part B :MT-12hour 300mg Fed (Standard) |
|---|---|---|---|
| ALT, low | 0 | 0 | 0 |
| ALT, normal or no change | 10 | 10 | 6 |
| ALT, high | 0 | 0 | 0 |
| Albumin, low | 0 | 0 | 0 |
| Albumin, normal or no change | 10 | 10 | 6 |
| Albumin, high | 0 | 0 | 0 |
| ALP, low | 0 | 0 | 0 |
| ALP, normal or no change | 10 | 10 | 6 |
| ALP, high | 0 | 0 | 0 |
| AST, low | 0 | 0 | 0 |
| AST, normal or no change | 10 | 10 | 6 |
| AST, high | 0 | 0 | 0 |
| Calcium, low | 0 | 0 | 0 |
| Calcium, normal or no change | 10 | 10 | 6 |
| Calcium, high | 0 | 0 | 0 |
| Creatinine, low | 0 | 0 | 0 |
| Creatinine, normal or no change | 10 | 10 | 6 |
| Creatinine, high | 0 | 0 | 0 |
| Glucose, low | 0 | 0 | 0 |
| Glucose, normal or no change | 10 | 10 | 6 |
| Glucose, high | 0 | 0 | 0 |
| Potassium, low | 0 | 0 | 0 |
| Potassium, normal or no change | 10 | 10 | 6 |
| Potassium, high | 0 | 0 | 0 |
| Sodium, low | 0 | 0 | 0 |
| Sodium, normal or no change | 10 | 10 | 6 |
| Sodium, high | 0 | 0 | 0 |
| Total Bilirubin, low | 0 | 0 | 0 |
| Total Bilirubin, normal or no change | 10 | 10 | 6 |
| Total Bilirubin, high | 0 | 0 | 0 |
Blood samples were collected to analyze hematology parameters like platelet count, WBC count, hemoglobin, hematocrit, total neutrophils, and lymphocytes. Participants are 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 are counted twice if the subject has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Participants with missing baseline value are assumed to have normal baseline value. Hematology parameters with potential clinical importance data has been reported. Data for worst-case post-Baseline has been reported.
| Participants | Part B: MT-12 120mg Fasted | Part B :MT-12 240mg Fasted | Part B :MT-12hour 300mg Fed (Standard) |
|---|---|---|---|
| Hematocrit, low | 0 | 0 | 0 |
| Hematocrit, normal or no change | 10 | 10 | 6 |
| Hematocrit, high | 0 | 0 | 0 |
| Hemoglobin, low | 0 | 0 | 0 |
| Hemoglobin, normal or no change | 10 | 10 | 6 |
| Hemoglobin, high | 0 | 0 | 0 |
| Lymphocytes, low | 0 | 0 | 0 |
| Lymphocytes, normal or no change | 10 | 10 | 6 |
| Lymphocytes, high | 0 | 0 | 0 |
| Platelet count, low | 0 | 0 | 0 |
| Platelet count, normal or no change | 10 | 10 | 6 |
| Platelet count, high | 0 | 0 | 0 |
| Total Neutrophils, low | 0 | 0 | 0 |
| Total Neutrophils, normal or no change | 10 | 10 | 6 |
| Total Neutrophils, high | 0 | 0 | 0 |
| WBC, low | 0 | 0 | 0 |
| WBC, normal or no change | 10 | 10 | 6 |
| WBC, high | 0 | 0 | 0 |
Urine samples were collected for analysis of specific gravity, potential of hydrogen ions, glucose, protein, blood and ketones by dipstick method. Microscopic examination were performed if blood or protein values were abnormal.
| Participants | Part B: MT-12 120mg Fasted | Part B :MT-12 240mg Fasted | Part B :MT-12hour 300mg Fed (Standard) |
|---|---|---|---|
| Number of Participants Abnormal Urinalysis Dipstick Results: Part B | 0 | 0 | 0 |
Blood samples were collected for analysis of clinical chemistry parameters like albumin, creatinine, glucose, potassium, sodium, AST, ALT, ALP, total bilirubin and calcium. Participants are 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 are counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Participants with missing Baseline value are assumed to have normal Baseline value. Clinical chemistry parameters with potential clinical importance data has been reported. Data for worst-case post-Baseline has been reported.
| Participants | Part C: IR 240mg Fasted | Part C:MM-12h 240mg Fasted | Part C:MM-12h 480mg Fasted | Part C:MM-12h 480mg Fed(Standard) | Part C:MM-12h 480mg Delayed Fed(Standard) | Part C: MM-12h 240mg Delayed Fed(High Fat) |
|---|---|---|---|---|---|---|
| ALT, low | 0 | 0 | 0 | 0 | 0 | 0 |
| ALT, normal or no change | 15 | 15 | 16 | 16 | 15 | 14 |
| ALT, high | 0 | 0 | 0 | 0 | 0 | 0 |
| Albumin, low | 0 | 0 | 0 | 0 | 0 | 0 |
| Albumin, normal or no change | 15 | 15 | 16 | 16 | 15 | 14 |
| Albumin, high | 0 | 0 | 0 | 0 | 0 | 0 |
| ALP, low | 0 | 0 | 0 | 0 | 0 | 0 |
| ALP, normal or no change | 15 | 15 | 16 | 16 | 15 | 14 |
| ALP, high | 0 | 0 | 0 | 0 | 0 | 0 |
| AST, low | 0 | 0 | 0 | 0 | 0 | 0 |
| AST, normal or no change | 15 | 15 | 16 | 16 | 15 | 14 |
| AST, high | 0 | 0 | 0 | 0 | 0 | 0 |
| Calcium, low | 0 | 0 | 0 | 0 | 0 | 0 |
| Calcium, normal or no change | 15 | 15 | 16 | 16 | 15 | 14 |
| Calcium, high | 0 | 0 | 0 | 0 | 0 | 0 |
| Creatinine, low | 0 | 0 | 0 | 0 | 0 | 0 |
| Creatinine, normal or no change | 15 | 15 | 16 | 16 | 15 | 14 |
| Creatinine, high | 0 | 0 | 0 | 0 | 0 | 0 |
| Glucose, low | 0 | 0 | 0 | 0 | 0 | 0 |
| Glucose, normal or no change | 15 | 15 | 16 | 16 | 15 | 14 |
| Glucose, high | 0 | 0 | 0 | 0 | 0 | 0 |
| Potassium, low | 0 | 0 | 0 | 0 | 0 | 0 |
| Potassium, normal or no change | 15 | 15 | 16 | 16 | 15 | 14 |
| Potassium, high | 0 | 0 | 0 | 0 | 0 | 0 |
| Sodium, low | 0 | 0 | 0 | 0 | 0 | 0 |
| Sodium, normal or no change | 15 | 15 | 16 | 16 | 15 | 14 |
| Sodium, high | 0 | 0 | 0 | 0 | 0 | 0 |
| Total Bilirubin, low | 0 | 0 | 0 | 0 | 0 | 0 |
| Total Bilirubin, normal or no change | 15 | 15 | 15 | 16 | 14 | 14 |
| Total Bilirubin, high | 0 | 0 | 1 | 0 | 1 | 14 |
Blood samples were collected to analyze hematology parameters like platelet count, WBC count, hemoglobin, hematocrit, total neutrophils, and lymphocytes. Participants are 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 are counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Participants with missing Baseline value are assumed to have normal Baseline value. Hematology parameters with potential clinical importance data has been reported. Data for worst-case post-Baseline has been reported.
| Participants | Part C: IR 240mg Fasted | Part C:MM-12h 240mg Fasted | Part C:MM-12h 480mg Fasted | Part C:MM-12h 480mg Fed(Standard) | Part C:MM-12h 480mg Delayed Fed(Standard) | Part C: MM-12h 240mg Delayed Fed(High Fat) |
|---|---|---|---|---|---|---|
| Hematocrit, low | 0 | 0 | 0 | 0 | 0 | 0 |
| Hematocrit, normal or no change | 15 | 15 | 16 | 16 | 15 | 14 |
| Hematocrit, high | 0 | 0 | 0 | 0 | 0 | 0 |
| Hemoglobin, low | 0 | 0 | 0 | 0 | 0 | 0 |
| Hemoglobin, normal or no change | 15 | 15 | 16 | 16 | 15 | 14 |
| Hemoglobin, high | 0 | 0 | 0 | 0 | 0 | 0 |
| Lymphocytes, low | 0 | 0 | 0 | 0 | 0 | 0 |
| Lymphocytes, normal or no change | 15 | 15 | 16 | 16 | 15 | 14 |
| Lymphocytes, high | 0 | 0 | 0 | 0 | 0 | 0 |
| Platelet count, low | 0 | 0 | 0 | 0 | 0 | 0 |
| Platelet count, normal or no change | 15 | 15 | 16 | 16 | 15 | 14 |
| Platelet count, high | 0 | 0 | 0 | 0 | 0 | 0 |
| Total Neutrophils, low | 0 | 0 | 0 | 0 | 0 | 0 |
| Total Neutrophils, normal or no change | 15 | 15 | 16 | 16 | 15 | 14 |
| Total Neutrophils, high | 0 | 0 | 0 | 0 | 0 | 0 |
| WBC, low | 0 | 0 | 0 | 0 | 0 | 0 |
| WBC, normal or no change | 15 | 15 | 16 | 16 | 15 | 14 |
| WBC, high | 0 | 0 | 0 | 0 | 0 | 0 |
Urine samples were collected for analysis of specific gravity, potential of hydrogen ions, glucose, protein, blood and ketones by dipstick method. Microscopic examination were performed if blood or protein values were abnormal.
| Participants | Part C: IR 240mg Fasted | Part C:MM-12h 240mg Fasted | Part C:MM-12h 480mg Fasted | Part C:MM-12h 480mg Fed(Standard) | Part C:MM-12h 480mg Delayed Fed(Standard) | Part C: MM-12h 240mg Delayed Fed(High Fat) |
|---|---|---|---|---|---|---|
| Number of Participants Abnormal Urinalysis Dipstick Results: Part C | 0 | 0 | 0 | 0 | 0 | 0 |
Single 12-lead ECGs was obtained using an ECG machine. PR, QRS, QT and Corrected QT (QTc) intervals were measured in semi-supine or supine position. Number of participants with any visit post-Baseline abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported. Data for worst-case post-Baseline has been reported.
| Participants | Part A: MT-12hour 120mg Fasted | Part A: MT-8hour 120mg Fasted | Part A: MT-12hour 120mg Fed (High Fat) | Part A: IR 120mg Fasted |
|---|---|---|---|---|
| Abnormal, not clinically significant | 6 | 8 | 9 | 9 |
| Abnormal, clinically significant | 1 | 0 | 0 | 0 |
Single 12-lead ECGs was obtained using an ECG machine. PR, QRS, QT and QTc intervals were measured in semi-supine or supine position. Number of participants with any visit post-Baseline abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported. Data for worst-case post-Baseline has been reported.
| Participants | Part B: MT-12 120mg Fasted | Part B :MT-12 240mg Fasted | Part B :MT-12hour 300mg Fed (Standard) |
|---|---|---|---|
| Abnormal, not clinically significant | 4 | 4 | 2 |
| Abnormal, clinically significant | 0 | 0 | 0 |
Single 12-lead ECGs was obtained using an ECG machine. PR, QRS, QT and QTc intervals were measured in semi-supine or supine position. Number of participants with any visit post-Baseline abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported. Data for worst-case post-Baseline has been reported.
| Participants | Part C: IR 240mg Fasted | Part C:MM-12h 240mg Fasted | Part C:MM-12h 480mg Fasted | Part C:MM-12h 480mg Fed(Standard) | Part C:MM-12h 480mg Delayed Fed(Standard) | Part C: MM-12h 240mg Delayed Fed(High Fat) |
|---|---|---|---|---|---|---|
| Abnormal, not clinically significant | 1 | 4 | 7 | 5 | 6 | 3 |
| Abnormal, clinically significant | 0 | 0 | 0 | 0 | 0 | 0 |
Systolic blood pressure (SBP) and diastolic blood pressure (DBP) was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
| Millimeters of mercury | Part A: IR 120mg Fasted | Part A: MT-12hour 120mg Fasted | Part A: MT-8hour 120mg Fasted | Part A: MT-12hour 120mg Fed (High Fat) |
|---|---|---|---|---|
| SBP, Day 1, 2 hours, n=16,16, 13,16 | -1.4 ± 13.46 | 4.3 ± 10.70 | -0.2 ± 16.53 | -6.2 ± 11.20 |
| SBP,Day 1, 12 hours, n=15,16, 13,16 | -1.6 ± 14.05 | -2.5 ± 14.27 | -6.2 ± 12.34 | -2.9 ± 18.70 |
| SBP,Day 2, 24 hours, n=16,16, 13,16 | 7.4 ± 13.86 | -2.7 ± 9.76 | -6.2 ± 11.22 | -3.9 ± 14.11 |
| DBP, Day 1, 2 hours, n=16,16, 13,16 | 0.3 ± 7.33 | 3.0 ± 8.12 | -1.8 ± 7.81 | -4.4 ± 8.94 |
| DBP,Day 1, 12 hours, n=16,16, 13,16 | -3.9 ± 10.01 | -3.6 ± 9.87 | -3.0 ± 9.27 | -3.9 ± 9.02 |
| DBP,Day 2, 24 hours, n=16,16, 13,16 | 2.1 ± 8.51 | 0.7 ± 7.60 | -1.7 ± 7.79 | -1.1 ± 8.82 |
Heart rate was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
| Beats per minute | Part A: IR 120mg Fasted | Part A: MT-12hour 120mg Fasted | Part A: MT-8hour 120mg Fasted | Part A: MT-12hour 120mg Fed (High Fat) |
|---|---|---|---|---|
| Day 1, 2 hours | -4.4 ± 5.11 | -0.3 ± 4.88 | -2.5 ± 7.62 | 3.9 ± 7.48 |
| Day 1, 12 hours | 4.8 ± 6.06 | 5.2 ± 3.94 | 5.8 ± 5.57 | 7.5 ± 9.93 |
| Day 2, 24 hours | 1.5 ± 9.41 | -2.1 ± 6.31 | 0.6 ± 7.14 | 0.9 ± 7.62 |
Respiration rate was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value
| Breaths per minute | Part A: IR 120mg Fasted | Part A: MT-12hour 120mg Fasted | Part A: MT-8hour 120mg Fasted | Part A: MT-12hour 120mg Fed (High Fat) |
|---|---|---|---|---|
| Day 1, 2 hours | -0.4 ± 1.67 | 0.8 ± 1.65 | 0.0 ± 1.00 | -1.5 ± 2.50 |
| Day 1, 12 hours | -0.6 ± 1.71 | -0.1 ± 1.82 | -0.2 ± 1.21 | -2.4 ± 2.63 |
| Day 2, 24 hours | 1.3 ± 2.15 | -0.1 ± 1.54 | -1.5 ± 1.51 | -1.4 ± 2.13 |
Body temperature was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
| Degree Celsius | Part A: IR 120mg Fasted | Part A: MT-12hour 120mg Fasted | Part A: MT-8hour 120mg Fasted | Part A: MT-12hour 120mg Fed (High Fat) |
|---|---|---|---|---|
| Day 1, 2 hours | 0.02 ± 0.152 | 0.18 ± 0.180 | 0.05 ± 0.145 | 0.14 ± 0.126 |
| Day 1, 12 hours | 0.07 ± 0.139 | -0.04 ± 0.145 | 0.13 ± 0.118 | 0.11 ± 0.173 |
| Day 2, 24 hours | 0.04 ± 0.182 | 0.07 ± 0.095 | 0.12 ± 0.114 | 0.12 ± 0.161 |
SBP and DBP was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
| Millimeters of mercury | Part B: MT-12 120mg Fasted | Part B :MT-12 240mg Fasted | Part B :MT-12hour 300mg Fed (Standard) |
|---|---|---|---|
| SBP, Day 1, 2 hours | -0.5 ± 7.40 | 5.4 ± 7.37 | 1.2 ± 7.08 |
| SBP,Day 1, 12 hours | 2.7 ± 7.75 | 1.5 ± 8.86 | 1.0 ± 10.73 |
| SBP,Day 2, Pre-dose | -0.1 ± 5.26 | 3.5 ± 7.76 | 1.8 ± 6.62 |
| SBP,Day 3, Pre-dose | -1.0 ± 9.35 | 1.1 ± 5.09 | -0.7 ± 14.09 |
| SBP,Day 3, 2 hours | 2.0 ± 8.37 | 5.5 ± 9.51 | -3.3 ± 9.14 |
| SBP,Day 3, 12 hours | 2.4 ± 11.55 | 7.4 ± 14.17 | 3.8 ± 8.21 |
| SBP,Day 4, 24 hours | 2.9 ± 9.22 | 6.1 ± 5.04 | 6.0 ± 11.24 |
| DBP, Day 1, 2 hours | 2.4 ± 7.31 | 2.1 ± 7.16 | -4.0 ± 4.20 |
| DBP,Day 1, 12 hours | -1.7 ± 5.50 | -2.2 ± 4.59 | -5.7 ± 4.03 |
| DBP,Day 2, Pre-dose | -1.5 ± 4.55 | 2.0 ± 7.47 | -2.7 ± 6.56 |
| DBP,Day 3, Pre-dose | 2.6 ± 8.57 | 1.3 ± 6.65 | 1.3 ± 4.50 |
| DBP,Day 3, 2 hours | 3.1 ± 7.00 | 4.0 ± 5.31 | -5.8 ± 3.87 |
| DBP,Day 3, 12 hours | -1.4 ± 7.78 | -1.4 ± 5.72 | -2.5 ± 2.81 |
| DBP,Day 4, 24 hours | 3.0 ± 5.56 | 4.6 ± 4.77 | 1.3 ± 6.65 |
Heart rate was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
| Beats per minute | Part B: MT-12 120mg Fasted | Part B :MT-12 240mg Fasted | Part B :MT-12hour 300mg Fed (Standard) |
|---|---|---|---|
| Day 1, 2 hours | 0.0 ± 5.50 | -2.4 ± 5.38 | 7.3 ± 6.89 |
| Day 1, 12 hours | 10.0 ± 4.00 | 8.8 ± 5.22 | 10.5 ± 3.78 |
| Day 2, Pre-dose | -0.1 ± 4.68 | -0.8 ± 6.37 | -1.8 ± 2.71 |
| Day 3, Pre-dose | 2.3 ± 4.74 | -0.1 ± 5.88 | 1.5 ± 5.43 |
| Day 3, 2 hours | 1.2 ± 5.37 | -0.3 ± 5.36 | 4.0 ± 2.28 |
| Day 3, 12 hours | 8.6 ± 4.58 | 10.6 ± 7.26 | 7.7 ± 5.28 |
| Day 4, 24 hours | 4.7 ± 8.64 | 6.7 ± 10.01 | 0.3 ± 2.58 |
Respiration rate was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value
| Breaths per minute | Part B: MT-12 120mg Fasted | Part B :MT-12 240mg Fasted | Part B :MT-12hour 300mg Fed (Standard) |
|---|---|---|---|
| Day 1, 2 hours | 0.5 ± 2.27 | -2.0 ± 2.00 | -1.2 ± 3.54 |
| Day 1, 12 hours | -0.1 ± 1.37 | -2.5 ± 2.17 | -1.5 ± 2.35 |
| Day 2, Pre-dose | -0.3 ± 1.49 | -0.5 ± 2.07 | -0.5 ± 2.74 |
| Day 3, Pre-dose | -0.7 ± 2.67 | -0.5 ± 1.43 | 1.5 ± 2.26 |
| Day 3, 2 hours | -1.3 ± 2.36 | -1.0 ± 2.21 | -0.7 ± 2.16 |
| Day 3, 12 hours | 0.3 ± 3.02 | -1.3 ± 2.16 | -0.8 ± 1.33 |
| Day 4, 24 hours | -0.8 ± 1.87 | -1.0 ± 1.89 | -0.3 ± 2.42 |
Body temperature was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
| Degree Celsius | Part B: MT-12 120mg Fasted | Part B :MT-12 240mg Fasted | Part B :MT-12hour 300mg Fed (Standard) |
|---|---|---|---|
| Day 1, 2 hours | 0.03 ± 0.298 | -0.01 ± 0.233 | 0.00 ± 0.110 |
| Day 1, 12 hours | 0.06 ± 0.181 | 0.08 ± 0.274 | 0.07 ± 0.082 |
| Day 2, Pre-dose | 0.04 ± 0.184 | -0.04 ± 0.158 | 0.12 ± 0.133 |
| Day 3, Pre-dose | 0.04 ± 0.135 | 0.07 ± 0.271 | 0.23 ± 0.151 |
| Day 3, 2 hours | -0.03 ± 0.149 | 0.01 ± 0.260 | -0.08 ± 0.147 |
| Day 3, 12 hours | 0.01 ± 0.191 | 0.05 ± 0.242 | 0.05 ± 0.138 |
| Day 4, 24 hours | 0.04 ± 0.171 | 0.11 ± 0.247 | 0.00 ± 0.089 |
SBP and DBP was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
| Millimeters of mercury | Part C: IR 240mg Fasted | Part C:MM-12h 240mg Fasted | Part C:MM-12h 480mg Fasted | Part C:MM-12h 480mg Fed(Standard) | Part C:MM-12h 480mg Delayed Fed(Standard) | Part C: MM-12h 240mg Delayed Fed(High Fat) |
|---|---|---|---|---|---|---|
| SBP, Day 1, 2 hours | -3.3 ± 7.93 | -0.6 ± 7.50 | -0.6 ± 6.16 | -4.9 ± 9.18 | 1.1 ± 16.02 | -0.2 ± 11.44 |
| SBP,Day1, 12 hours | -3.1 ± 10.04 | -2.6 ± 8.34 | 1.4 ± 12.06 | 0.1 ± 10.81 | -7.3 ± 14.92 | 0.9 ± 16.03 |
| SBP,Day2, 24 hours | 4.9 ± 8.02 | -1.4 ± 6.71 | -1.6 ± 8.39 | -3.1 ± 8.50 | 2.6 ± 10.84 | -7.5 ± 10.58 |
| DBP, Day 1, 2 hours | -0.1 ± 7.41 | -0.7 ± 6.43 | 2.0 ± 6.92 | -4.3 ± 6.94 | -0.6 ± 7.88 | -1.9 ± 5.50 |
| DBP,Day1, 12 hours | -2.1 ± 7.23 | -1.1 ± 6.36 | -3.1 ± 6.53 | -0.6 ± 8.02 | -3.7 ± 9.61 | 0.0 ± 8.38 |
| DBP,Day2, 24 hours | 0.4 ± 7.21 | 1.0 ± 4.88 | -0.5 ± 6.64 | 2.8 ± 6.37 | 0.7 ± 7.49 | 2.4 ± 6.21 |
Heart rate was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
| Beats per minute | Part C: IR 240mg Fasted | Part C:MM-12h 240mg Fasted | Part C:MM-12h 480mg Fasted | Part C:MM-12h 480mg Fed(Standard) | Part C:MM-12h 480mg Delayed Fed(Standard) | Part C: MM-12h 240mg Delayed Fed(High Fat) |
|---|---|---|---|---|---|---|
| Day 1, 2 hours | 2.1 ± 6.94 | -5.3 ± 6.19 | 0.0 ± 6.86 | 7.3 ± 6.56 | 8.2 ± 5.72 | 8.2 ± 7.32 |
| Day 1, 12 hours | 6.8 ± 6.20 | 6.5 ± 9.73 | 11.2 ± 9.65 | 10.3 ± 6.94 | 9.3 ± 8.28 | 8.6 ± 6.99 |
| Day 2, 24 hours | 1.8 ± 5.44 | 0.1 ± 6.41 | -0.4 ± 3.77 | 0.4 ± 5.80 | -0.9 ± 6.19 | 1.6 ± 7.74 |
Respiration rate was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
| Breaths per minute | Part C: IR 240mg Fasted | Part C:MM-12h 240mg Fasted | Part C:MM-12h 480mg Fasted | Part C:MM-12h 480mg Fed(Standard) | Part C:MM-12h 480mg Delayed Fed(Standard) | Part C: MM-12h 240mg Delayed Fed(High Fat) |
|---|---|---|---|---|---|---|
| Day 1, 2 hours | 1.7 ± 3.37 | 0.6 ± 2.03 | 0.9 ± 2.90 | -1.1 ± 2.95 | 1.8 ± 1.74 | 0.1 ± 2.76 |
| Day 1, 12 hours | 1.1 ± 2.59 | 1.0 ± 2.85 | 0.6 ± 2.66 | -1.1 ± 2.90 | -0.3 ± 2.61 | 0.5 ± 1.51 |
| Day 2, 24 hours | 1.6 ± 3.25 | 0.4 ± 3.07 | 0.6 ± 4.00 | -2.2 ± 2.66 | 1.8 ± 2.31 | 0.4 ± 3.34 |
Body temperature was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.
| Degree Celsius | Part C: IR 240mg Fasted | Part C:MM-12h 240mg Fasted | Part C:MM-12h 480mg Fasted | Part C:MM-12h 480mg Fed(Standard) | Part C:MM-12h 480mg Delayed Fed(Standard) | Part C: MM-12h 240mg Delayed Fed(High Fat) |
|---|---|---|---|---|---|---|
| Day 1, 2 hours | -0.10 ± 0.245 | -0.05 ± 0.192 | -0.07 ± 0.215 | 0.23 ± 0.275 | 0.01 ± 0.228 | 0.10 ± 0.301 |
| Day 1, 12 hours | 0.02 ± 0.197 | -0.11 ± 0.229 | -0.05 ± 0.271 | 0.12 ± 0.307 | -0.14 ± 0.241 | -0.10 ± 0.266 |
| Day 2, 24 hours | -0.04 ± 0.256 | 0.15 ± 0.261 | -0.00 ± 0.239 | 0.10 ± 0.278 | -0.09 ± 0.269 | -0.01 ± 0.241 |
Collected over Non-serious AEs and SAEs were collected up to Day 43 for Part A and Part C and up to Day 22 for Part B. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part A:IR 120mg Fasted | 0/16 (0%) | 0/16 (0%) | 4/16 (25%) |
| Part A:MT-12hour 120mg Fasted | 1/16 (6.3%) | 1/16 (6.3%) | 5/16 (31.3%) |
| Part A:MT-8hour 120mg Fasted | 0/13 (0%) | 0/13 (0%) | 1/13 (7.7%) |
| Part A:MT-12hour 120mg Fed (High Fat) | 0/16 (0%) | 0/16 (0%) | 2/16 (12.5%) |
| Part B:MT-12hour 120mg Fasted | 0/10 (0%) | 0/10 (0%) | 1/10 (10%) |
| Part B:MT-12hour 240mg Fasted | 0/10 (0%) | 0/10 (0%) | 3/10 (30%) |
| Part B:MT-12hour 300mg Fed (Standard) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) |
| Part C:IR 240mg Fasted | 0/15 (0%) | 0/15 (0%) | 3/15 (20%) |
| Part C:MM-12hour 240mg Fasted | 0/15 (0%) | 0/15 (0%) | 3/15 (20%) |
| Part C:MM-12hour 480mg Fasted | 0/16 (0%) | 0/16 (0%) | 3/16 (18.8%) |
| Part C:MM-12hour 480mg Fed (Standard) | 0/16 (0%) | 0/16 (0%) | 4/16 (25%) |
| Part C:MM-12hour 480mg Delayed Fed (Standard) | 0/15 (0%) | 0/15 (0%) | 2/15 (13.3%) |
| Part C:MM-12hour 240mg Delayed Fed (High Fat) | 0/14 (0%) | 0/14 (0%) | 1/14 (7.1%) |
| Event | Part A:IR 120mg Fasted | Part A:MT-12hour 120mg Fasted | Part A:MT-8hour 120mg Fasted | Part A:MT-12hour 120mg Fed (High Fat) | Part B:MT-12hour 120mg Fasted | Part B:MT-12hour 240mg Fasted | Part B:MT-12hour 300mg Fed (Standard) | Part C:IR 240mg Fasted | Part C:MM-12hour 240mg Fasted | Part C:MM-12hour 480mg Fasted | Part C:MM-12hour 480mg Fed (Standard) | Part C:MM-12hour 480mg Delayed Fed (Standard) | Part C:MM-12hour 240mg Delayed Fed (High Fat) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AsphyxiaRespiratory, thoracic and mediastinal disorders | 0/16 | 1/16 | 0/13 | 0/16 | 0/10 | 0/10 | 0/6 | 0/15 | 0/15 | 0/16 | 0/16 | 0/15 | 0/14 |
| Event | Part A:IR 120mg Fasted | Part A:MT-12hour 120mg Fasted | Part A:MT-8hour 120mg Fasted | Part A:MT-12hour 120mg Fed (High Fat) | Part B:MT-12hour 120mg Fasted | Part B:MT-12hour 240mg Fasted | Part B:MT-12hour 300mg Fed (Standard) | Part C:IR 240mg Fasted | Part C:MM-12hour 240mg Fasted | Part C:MM-12hour 480mg Fasted | Part C:MM-12hour 480mg Fed (Standard) | Part C:MM-12hour 480mg Delayed Fed (Standard) | Part C:MM-12hour 240mg Delayed Fed (High Fat) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Injury associated with deviceGeneral disorders | 0/16 | 0/16 | 0/13 | 0/16 | 0/10 | 1/10 | 1/6 | 0/15 | 0/15 | 0/16 | 0/16 | 0/15 | 0/14 |
| HeadacheNervous system disorders | 1/16 | 0/16 | 0/13 | 0/16 | 1/10 | 0/10 | 0/6 | 2/15 | 1/15 | 2/16 | 2/16 | 1/15 | 1/14 |
| NasopharyngitisInfections and infestations | 2/16 | 1/16 | 0/13 | 0/16 | 0/10 | 0/10 | 0/6 | 0/15 | 1/15 | 0/16 | 0/16 | 0/15 | 0/14 |
| Back painMusculoskeletal and connective tissue disorders | 0/16 | 2/16 | 0/13 | 1/16 | 0/10 | 0/10 | 0/6 | 0/15 | 0/15 | 0/16 | 0/16 | 0/15 | 0/14 |
| Catheter site bruiseGeneral disorders | 0/16 | 2/16 | 0/13 | 0/16 | 0/10 | 0/10 | 0/6 | 0/15 | 0/15 | 0/16 | 0/16 | 1/15 | 0/14 |
| Vessel puncture site bruiseGeneral disorders | 0/16 | 0/16 | 0/13 | 0/16 | 1/10 | 0/10 | 0/6 | 0/15 | 0/15 | 1/16 | 0/16 | 1/15 | 0/14 |
| Catheter site painGeneral disorders | 0/16 | 0/16 | 0/13 | 0/16 | 1/10 | 0/10 | 0/6 | 0/15 | 0/15 | 0/16 | 0/16 | 0/15 | 0/14 |
| Catheter site swellingGeneral disorders | 0/16 | 0/16 | 0/13 | 0/16 | 1/10 | 0/10 | 0/6 | 0/15 | 0/15 | 0/16 | 0/16 | 0/15 | 0/14 |
| FatigueGeneral disorders | 0/16 | 0/16 | 0/13 | 0/16 | 0/10 | 1/10 | 0/6 | 0/15 | 0/15 | 0/16 | 0/16 | 0/15 | 0/14 |
| Vessel puncture site painGeneral disorders | 0/16 | 0/16 | 0/13 | 0/16 | 0/10 | 1/10 | 0/6 | 0/15 | 0/15 | 0/16 | 0/16 | 0/15 | 0/14 |
| Age, Continuous(Years) | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF | Total |
|---|---|---|---|---|
| Mean | 49.2 ± 14.10 | 47.8 ± 13.43 | 45.3 ± 12.22 | 47.5 ± 13.12 |
| Sex: Female, Male(Participants) | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF | Total |
|---|---|---|---|---|
| Female | 8 | 4 | 7 | 19 |
| Male | 11 | 6 | 9 | 26 |
| Race/Ethnicity, Customized(Participants) | MT-12hr Fasted/MT-8hr Fasted/IR Fasted/MT-12hr Fed (High Fat) | MT 120mg Fasted/MT 240mg Fasted/ MT 300mg Fed (Standard) | MM240 Fast/IR240 Fast/MM480 Fast/MM480 Fed/MM480 DF/MM240 DF | Total |
|---|---|---|---|---|
| Asian - East Asian Heritage | 1 | 0 | 1 | 2 |
| White - White/Caucasian/European Heritage | 18 | 10 | 14 | 42 |
| Asian - South East Asian Heritage | 0 | 0 | 1 | 1 |
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Plan to share: Yes — IPD for this study is available via the Clinical Study Data Request site
Supporting information: Study protocol, Sap, Icf, Csr
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