This is an open-label, single-sequence, 1-way drug-drug interaction study to investigate the effect of GSK3640254 on the pharmacokinetics of a combination oral contraceptive containing ethinyl estradiol (EE) and levonorgestrel (LNG). Effective contraception for women infected with human immunodeficiency virus (HIV) is important in the prevention of unplanned pregnancies. The study will consist of a screening period of 28 days, check-in (Day -4), a run-in period and a treatment period. During the run-in period, subjects will be administered Portia® (0.03 milligrams \[mg\] EE/0.15 mg LNG) once daily on Days -3 to -1. Subjects will then be administered Portia once daily on Days 1 to 10 of treatment period A followed by administration of Portia once daily along with GSK3640254 200 mg on Days 11 to 21 of treatment period B. The duration of the study is approximately 8 weeks, including Screening and Run-in. Portia is a registered trademark of Teva Pharmaceuticals USA.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
23
GSK3640254 will be available as a 100 mg capsule. Subjects will be administered 200 mg GSK3640254 once daily via the oral route on Days 11 to 21.
Portia will be available in the form of tablets containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel.
GSK Investigational Site
Austin, Texas, United States
Period 1: Area Under the Plasma Concentration-time Curve From Time 0 to the End of the Dosing Interval at Steady State (AUC [0-tau]) of EE
Blood samples were collected at indicated time points for the analysis of AUC (0-tau) of EE. PK parameters were calculated by standard non-compartmental analysis. The PK population included all participants who underwent plasma PK sampling and had evaluable PK parameters estimated.
Time frame: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours
Period 2: AUC (0-tau) of EE
Blood samples were collected at indicated time points for the analysis of AUC (0-tau) of EE. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 and 24 hours post dose
Period 1:AUC (0-tau) of LNG
Blood samples were collected at indicated time points for the analysis of AUC (0-tau) of LNG. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours
Period 2: AUC (0-tau) of LNG
Blood samples were collected at indicated time points for the analysis of AUC (0-tau) of LNG. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 and 24 hours post dose
Period 1: Maximum Observed Concentration (Cmax) and Plasma Concentration at the End of the Dosing Interval (Ctau) of EE
Blood samples were collected at indicated time points for the analysis of Cmax and Ctau of EE. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours
Period 2: Cmax and Ctau of EE
Blood samples were collected at indicated time points for the analysis of Cmax and Ctau of EE. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 and 24 hours
Period 1:Cmax and Ctau of LNG
Blood samples were collected at indicated time points for the analysis of Cmax and Ctau of LNG. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours
Period 2: Cmax and Ctau of LNG
Blood samples were collected at indicated time points for the analysis of Cmax and Ctau of LNG. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 and 24 hours post dose
Period 1: Effect of GSK3640254 on PD of EE/LNG- Serum Progesterone Level
Serum samples were collected for the analysis of progesterone concentration levels when GSK3640254 is co-administered with EE/LNG. PD concentration Population comprised of all participants who underwent plasma PD sampling and had evaluable PD assay results.
Time frame: At Day 1 and Day 10
Period 2: Effect of GSK3640254 on PD of EE/LNG- Serum Progesterone Level
Serum samples were collected for the analysis progesterone concentration levels when GSK3640254 is co-administered with EE/LNG.
Time frame: At Days 11, 21 and 22
Period 1: Absolute Values of Effect of GSK3640254 on Luteinizing Hormone (LH) and Follicle-stimulating Hormone (FSH)
Serum samples were collected for the analysis of effect of GSK3640254 on LH and FSH.
Time frame: At Day 1 and Day 10
Period 2: Absolute Values of Effect of GSK3640254 on LH and FSH
Serum samples were collected for the analysis of effect of GSK3640254 on LH and FSH.
Time frame: At Days 11, 21 and 22
Period 2: AUC (0-tau) of GSK3640254
Blood samples were collected at indicated time points for the analysis of AUC (0-tau) of GSK3640254. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Day 21: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8 and 12 and 24 hours post dose
Period 2: Cmax and Ctau of GSK3640254
Blood samples were collected at indicated time points for the analysis of Cmax and Ctau of GSK3640254. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Day 21: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8 and 12 and 24 hours post dose
Period 2: Apparent Terminal Phase Half-life (t1/2) of GSK3640254
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Blood samples were collected at indicated time points for the analysis of t1/2 of GSK3640254. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Day 21: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8 and 12 hours; Day 22: 24 hours; Day 23: 48 hours; Day 24: 72 hours and Day 25: 96 hours
Period 2: Time of Maximum Observed Concentration (Tmax) of GSK3640254
Blood samples were collected at indicated time points for the analysis of Tmax of GSK3640254. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Day 21: Pre-dose, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8 and 12 and 24 hours post dose
Period 1: t1/2 of EE
Blood samples were collected at indicated time points for the analysis of t1/2 of EE. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours
Period 2: t1/2 of EE
Blood samples were collected at indicated time points for the analysis of t1/2 of EE. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 22: 24 hours; Day 23: 48 hours and Day 24: 72 hours
Period 1: Tmax of EE
Blood samples were collected at indicated time points for the analysis of Tmax of EE. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours
Period 2: Tmax of EE
Blood samples were collected at indicated time points for the analysis of Tmax of EE. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 22: 24 hours; Day 23: 48 hours and Day 24: 72 hours
Period 1: t1/2 of LNG
Blood samples were collected at indicated time points for the analysis of t1/2 of LNG. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours
Period 2: t1/2 of LNG
Blood samples were collected at indicated time points for the analysis of t1/2 of LNG. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours; Day 22: 24 hours; Day 23: 48 hours and Day 24: 72 hours
Period 1: Tmax of LNG
Blood samples were collected at indicated time points for the analysis of Tmax of LNG. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours
Period 2: Tmax of LNG
Blood samples were collected at indicated time points for the analysis of Tmax of LNG. PK parameters were calculated by standard non-compartmental analysis.
Time frame: Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours; Day 22: 24 hours; Day 23: 48 hours and Day 24: 72 hours
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAE) (Treatment Period)
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. Safety Population comprised of all participants who received at least one dose of study medication.
Time frame: Up to Day 25
Number of Participants With Non-SAEs and SAE (Run-in Period)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before.
Time frame: From Day -3 to Day -1
Period 1: Change From Baseline in Clinical Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium and Blood Urea Nitrogen (BUN)
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and BUN. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in Clinical Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium and BUN
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and BUN. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Change From Baseline in Clinical Chemistry Parameters: Plasma Albumin, Globulin and Protein
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including plasma albumin, globulin and protein. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in Clinical Chemistry Parameters: Plasma Albumin, Globulin and Protein
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including plasma albumin, globulin and protein. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Change From Baseline in Clinical Chemistry Parameters: Plasma Amylase and Lipase
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including plasma amylase and lipase. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in Clinical Chemistry Parameters: Plasma Amylase and Lipase
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including plasma amylase and lipase. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Change From Baseline in Clinical Chemistry Parameters: Plasma Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT)
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Plasma creatine kinase, lactate dehydrogenase, ALT, ALP, AST and GGT. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in Clinical Chemistry Parameters: Plasma Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST and GGT
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Plasma creatine kinase, lactate dehydrogenase, ALT, ALP, AST and GGT. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Change From Baseline in Clinical Chemistry Parameters: Plasma Urate, Creatinine, Total Bilirubin and Direct Bilirubin
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Plasma urate, creatinine, total bilirubin and direct bilirubin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in Clinical Chemistry Parameters: Plasma Urate, Creatinine, Total Bilirubin and Direct Bilirubin
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Plasma urate, creatinine, total bilirubin and direct bilirubin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets
Blood samples were collected at indicated time points for the analysis of hematology parameters including Basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets
Blood samples were collected at indicated time points for the analysis of hematology parameters including Basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes mean corpuscular hemoglobin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes mean corpuscular hemoglobin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume
Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes mean corpuscular volume. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume
Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes mean corpuscular volume. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Change From Baseline in Hematology Parameter: Erythrocytes
Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in Hematology Parameter: Erythrocytes
Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Change From Baseline in Hematology Parameter: Hematocrit
Blood samples were collected at indicated time points for the analysis of hematology parameter hematocrit. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in Hematology Parameter: Hematocrit
Blood samples were collected at indicated time points for the analysis of hematology parameter hematocrit. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Change From Baseline in Hematology Parameter: Hemoglobin
Blood samples were collected at indicated time points for the analysis of hematology parameter hemoglobin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in Hematology Parameter: Hemoglobin
Blood samples were collected at indicated time points for the analysis of hematology parameter hemoglobin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Change From Baseline in Urine Concentration: Urine Specific Gravity
Urine samples were collected at indicated time points for the assessment of specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in Urine Concentration: Urine Specific Gravity
Urine samples were collected at indicated time points for the assessment of specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Change From Baseline in Urine Concentration: Urine Urobilinogen
Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in Urine Concentration: Urine Urobilinogen
Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Change From Baseline in Urine Concentration: Urine Potential of Hydrogen (pH)
Urine samples were collected at indicated time points for the assessment of Urinary pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in Urine Concentration: Urine pH
Urine samples were collected at indicated time points for the assessment of Urinary pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate
Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure heart rate. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in ECG Mean Heart Rate
Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure heart rate. Baseline is defined as the average of the triplicate predose assessments on Day 11. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 11, Pre-dose) and at Day 11: 2, 4, 6 hours, Day 15: 2, 4, 6 hours, Day 21 and 24
Period 1: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, Fridericia QT Correction Formula (QTcF) Interval, and Bazett QT Correction Formula (QTcB) Interval
Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure PR interval, QRS duration, QT Interval, QTcF Interval and QTcB interval. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF and QTcB Interval
Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure heart rate. Baseline is defined as the average of the triplicate predose assessments on Day 11. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 11, Pre-dose) and at Day 11: 2, 4, 6 hours, Day 15: 2, 4, 6 hours, Day 21 and 24
Period 1: Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP and DBP were assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline is defined as the average of the triplicate pre-dose assessments. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in Vital Signs: SBP and DBP
SBP and DBP were assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline is defined as as the average of the triplicate pre-dose assessments. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24
Period 1: Change From Baseline in Pulse Rate
Pulse rate was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline is defined as the average of the triplicate predose assessments. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in Pulse Rate
Pulse rate was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline is defined as the average of the triplicate predose assessments. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24
Period 1: Change From Baseline in Respiratory Rate
Respiratory rate was assessed at indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in Respiratory Rate
Respiratory rate was assessed at indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24
Period 1: Change From Baseline in Temperature
Temperature was assessed at indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Change From Baseline in Temperature
Temperature was assessed at indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time frame: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24
Period 1: Absolute Values of Clinical Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium and BUN
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and BUN. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of Clinical Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium and BUN
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and BUN. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Absolute Values of Clinical Chemistry Parameters: Plasma Albumin, Globulin and Protein
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including plasma albumin, globulin and protein. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of Clinical Chemistry Parameters: Plasma Albumin, Globulin and Protein
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including plasma albumin, globulin and protein. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Absolute Values of Clinical Chemistry Parameters: Plasma Amylase and Lipase
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including plasma amylase and lipase. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of Clinical Chemistry Parameters: Plasma Amylase and Lipase
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including plasma amylase and lipase. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Absolute Values of Clinical Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST and GGT
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including creatine kinase, lactate dehydrogenase, ALT, ALP, AST and GGT. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of Clinical Chemistry Parameters: Plasma Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST and GGT
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Plasma creatine kinase, lactate dehydrogenase, ALT, ALP, AST and GGT. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Absolute Values of Clinical Chemistry Parameters: Urate, Creatinine, Total Bilirubin and Direct Bilirubin
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Plasma urate, creatinine, total bilirubin and direct bilirubin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of Clinical Chemistry Parameters: Plasma Urate, Creatinine, Total Bilirubin and Direct Bilirubin
Blood samples were collected at indicated time points for the analysis of clinical chemistry parameters including Plasma urate, creatinine, total bilirubin and direct bilirubin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Absolute Values of Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets
Blood samples were collected at indicated time points for the analysis of hematology parameters including Basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets
Blood samples were collected at indicated time points for the analysis of hematology parameters including Basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Absolute Values of Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes mean corpuscular hemoglobin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes mean corpuscular hemoglobin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Absolute Values of Hematology Parameter: Erythrocytes Mean Corpuscular Volume
Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes mean corpuscular volume. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of Hematology Parameter: Erythrocytes Mean Corpuscular Volume
Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes mean corpuscular volume. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Absolute Values of Hematology Parameter: Erythrocytes
Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of Hematology Parameter: Erythrocytes
Blood samples were collected at indicated time points for the analysis of hematology parameter erythrocytes. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Absolute Values of Hematology Parameter: Hematocrit
Blood samples were collected at indicated time points for the analysis of hematology parameter hematocrit. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of Hematology Parameter: Hematocrit
Blood samples were collected at indicated time points for the analysis of hematology parameter hematocrit. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Absolute Values of Hematology Parameter: Hemoglobin
Blood samples were collected at indicated time points for the analysis of hematology parameter hemoglobin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of Hematology Parameter: Hemoglobin
Blood samples were collected at indicated time points for the analysis of hematology parameter hemoglobin. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Absolute Values of Urine Concentration: Urine Specific Gravity
Urine samples were collected at indicated time points for the assessment of specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of Urine Concentration: Urine Specific Gravity
Urine samples were collected at indicated time points for the assessment of specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Absolute Values of Urine Concentration: Urine Urobilinogen
Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of Urine Concentration: Urine Urobilinogen
Urine samples were collected at indicated time points for the assessment of urine urobilinogen. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Absolute Values of Urine Concentration: Urine pH
Urine samples were collected at indicated time points for the assessment of Urinary pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of Urine Concentration: Urine pH
Urine samples were collected at indicated time points for the assessment of Urinary pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Number of Participants With Abnormal Urinalysis Parameters Using Dipstick Method.
The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters (ketones, glucose, bilirubin, occult blood, nitrite and blood protein) can be read as positive, trace, 1+, 2+, 3+ and 4+ indicating proportional concentrations in the urine sample. Only participants with abnormal findings for urinalysis at any visit has been presented.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Number of Participants With Abnormal Urinalysis Parameters Using Dipstick Method.
The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters (ketones, glucose, bilirubin, occult blood, nitrite and blood protein) can be read as positive, trace, 1+, 2+, 3+ and 4+ indicating proportional concentrations in the urine sample. Only participants with abnormal findings for urinalysis at any visit has been presented.
Time frame: Baseline (Day 10) and at Days 21 and 24
Period 1: Absolute Values of ECG Mean Heart Rate
Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure heart rate. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of ECG Mean Heart Rate
Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure heart rate. Baseline is defined as the average of the triplicate predose assessments on Day 11.
Time frame: Baseline (Day 11, Pre-dose) and at Day 11: 2, 4, 6 hours, Day 15: 2, 4, 6 hours, Day 21 and 24
Period 1: Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval, and QTcB Interval
Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure PR interval, QRS duration, QT Interval, QTcF Interval and QTcB interval. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF and QTcB Interval
Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes using an automated ECG machine to measure PR Interval, QRS Duration, QT Interval, QTcF and QTcB Interval. Baseline is defined as the average of the triplicate predose assessments on Day 11.
Time frame: Baseline (Day 11, Pre-dose) and at Day 11- 2, 4, 6 hours, Day 15- 2, 4, 6 hours, Day 21 and 24
Period 1: Absolute Values of Vital Signs: SBP and DBP
SBP and DBP were assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline is defined as the average of the triplicate predose assessments on Day 11.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of Vital Signs: SBP and DBP
SBP and DBP were assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24
Period 1: Absolute Values of Pulse Rate
Pulse rate was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of Pulse Rate
Pulse rate was assessed in the semi-recumbent position with a completely automated device at indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24
Period 1: Absolute Values of Respiratory Rate
Respiratory rate was assessed indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of Respiratory Rate
Respiratory rate was assessed indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24
Period 1: Absolute Values of Temperature
Temperature was assessed at indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 1, Pre-dose) and at Day 10
Period 2: Absolute Values of Temperature
Temperature was assessed at indicated time-points. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment.
Time frame: Baseline (Day 11, Pre-dose) and at Days 15, 21 and 24