A Relative Bioavailability and Food-Effect Study of the Fixed Dose Combination of GSK3640254 and Dolutegravir (DTG) in Healthy Participants

HIV Infections Clinical Trial

Official title:

A Two-Part, Randomized, Open-Label, Single Dose, Crossover Clinical Study to Assess the Relative Bioavailability of Fixed-Dose Combinations of GSK3640254 and Dolutegravir and to Assess the Effect of Food on the Select Fixed Dose Combination of GSK3640254 and Dolutegravir in Healthy Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04857892
• Other study ID #: 213055
• Status: Completed
• Phase: Phase 1
• Start date: April 21, 2021
• Est. completion date: September 10, 2021

Study information

• Verified date: August 2023
• Source: ViiV Healthcare
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a two part study to compare the relative bioavailability (BA) of 2 fixed dose combinations (FDCs) of GSK3640254/DTG with GSK3640254 and DTG administered together as single agents (Part 1) and to assess the effect of food on the pharmacokinetic (PK) of the selected FDC of GSK3640254/DTG (Part 2).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: September 10, 2021
• Est. primary completion date: September 10, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent.

• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and ECG).

• Participants capable of giving signed informed consent.

Exclusion Criteria:

• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

• A pre-existing condition interfering with normal gastro intestinal anatomy or motility (for example [e.g.], gastroesophageal reflux disease, gastric ulcers, gastritis) or hepatic and/or renal function that could interfere with the absorption, metabolism, and/or excretion of the study intervention or render the participant unable to take oral study intervention.

• Prior cholecystectomy surgery (prior appendectomy is acceptable).

• Clinically significant illness, including viral syndromes within 3 weeks of dosing.

• Participant with known or suspected active Coronavirus disease (COVID)-19 infection or contact with an individual with known COVID-19, within 14 days of study enrollment.

• Current enrollment or past participation within the last 30 days before signing of consent in any other clinical study involving an investigational study intervention (including an investigational COVID vaccine) or any other type of medical research.

• Prior exposure to GSK3640254 or prior intolerance to DTG in this or another clinical study.

• Any positive (abnormal) response confirmed by the investigator on a screening clinician- or qualified designee-administered Columbia Suicide Severity Rating Scale (C-SSRS).

• Any significant arrhythmia or ECG finding (e.g., prior myocardial infarction in the past 3 months, symptomatic bradycardia, non-sustained or sustained atrial arrhythmias, non-sustained or sustained ventricular tachycardia, any degree of atrioventricular block, or conduction abnormality) which, in the opinion of the investigator or ViiV Healthcare (VH)/GlaxoSmithKline (GSK) medical monitor, will interfere with the safety for the individual participant.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• GSK3640254
GSK3640254 will be administered via oral route.
• DTG
DTG will be administered via oral route.
• GSK3640254/DTG
GSK3640254/DTG will be administered via oral route.

Locations

Country	Name	City	State
United States	GSK Investigational Site	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
ViiV Healthcare

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of GSK3640254	Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3640254.	Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period
Primary	Part 1: Area Under the Plasma Concentration-time Curve From Time 0 to Time t (AUC[0-t]) of GSK3640254	Blood samples were collected at indicated time points for PK analysis of GSK3640254.	Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period
Primary	Part 1: Maximum Observed Concentration (Cmax) of GSK3640254	Blood samples were collected at indicated time points for PK analysis of GSK3640254.	Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period
Primary	Part 1: AUC(0-inf) of DTG	Blood samples were collected at indicated time points for PK analysis of DTG.	Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period
Primary	Part 1: AUC(0-t) of DTG	Blood samples were collected at indicated time points for PK analysis of DTG.	Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period
Primary	Part 1: Cmax of DTG	Blood samples were collected at indicated time points for PK analysis of DTG.	Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period
Primary	Part 2: AUC(0-inf) of GSK3640254	Blood samples were collected at indicated time points for PK analysis of GSK3640254.	Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period
Primary	Part 2: AUC(0-t) of GSK3640254	Blood samples were collected at indicated time points for PK analysis of GSK3640254.	Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period.
Primary	Part 2: Cmax of GSK3640254	Blood samples were collected at indicated time points for PK analysis of GSK3640254.	Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period
Primary	Part 2: AUC(0-inf) of DTG	Blood samples were collected at indicated time points for PK analysis of DTG.	Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period
Primary	Part 2: AUC(0-t) of DTG	Blood samples were collected at indicated time points for PK analysis of DTG.	Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period
Primary	Part 2: Cmax of DTG	Blood samples were collected at indicated time points for PK analysis of DTG.	Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period
Secondary	Part 1: Number of Participants With Non-Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)	An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment. Adverse events which were not Serious Adverse Events were considered as Non-Serious adverse events.	Up to 17 days
Secondary	Part 2: Number of Participants With Non-SAEs and SAEs	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment. Adverse events which were not Serious Adverse Events were considered as Non-Serious adverse events.	Up to 9 days
Secondary	Part 1: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets	Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, and platelets. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 2: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets	Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelets. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Absolute Values for Hematology Parameter: Hemoglobin	Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 2: Absolute Values for Hematology Parameter: Hemoglobin	Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume	Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume	Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Absolute Values for Hematology Parameter: Erythrocytes	Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 2: Absolute Values for Hematology Parameter: Erythrocytes	Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Absolute Values for Hematology Parameters: Hematocrit	Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 2: Absolute Values for Hematology Parameters: Hematocrit	Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Absolute Values for Hematology Parameters: Erythrocytes Mean Corpuscular Hemoglobin	Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 2: Absolute Values for Hematology Parameters: Erythrocytes Mean Corpuscular Hemoglobin	Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets	Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, and platelets. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets	Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, and platelets. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Change From Baseline in Hematology Parameter: Hemoglobin	Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 2: Change From Baseline in Hematology Parameter: Hemoglobin	Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume	Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume	Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Change From Baseline in Hematology Parameter: Erythrocytes	Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 2: Change From Baseline in Hematology Parameter: Erythrocytes	Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Change From Baseline in Hematology Parameter: Hematocrit	Blood samples were collected to analyze the hematology parameter: hemotocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 2: Change From Baseline in Hematology Parameter: Hematocrit	Blood samples were collected to analyze the hematology parameters: hemotocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin	Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5, and 7
Secondary	Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin	Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Absolute Values for Clinical Chemistry Parameters: Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Lactate Dehydrogenase (LDH), Creatinine Kinase (CK)	Blood samples were collected to analyze the chemistry parameters: ALT, ALP, AST, GGT, LDH, CK. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1), and Days 2, 5, and 7
Secondary	Part 2: Absolute Values of Clinical Chemistry Parameters: ALT, ALP, AST, GGT, LDH, CK	Blood samples were collected to analyze the chemistry parameters: ALT, ALP, AST, GGT, LDH, CK. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Absolute Values of Clinical Chemistry Parameters: Calcium, Carbon-dioxide (CO2), Chloride, Glucose, Potassium, Sodium, Urea Nitrogen, Phosphorus, Triglycerides, Cholesterol, and Anion Gap	Blood samples were collected to analyze the chemistry parameters: calcium, CO2, chloride, glucose, potassium, sodium, urea nitrogen, phosphorus, triglycerides, cholesterol, and anion gap. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1), and Days 2, 5, and 7
Secondary	Part 2: Absolute Values of Clinical Chemistry Parameters: Calcium, CO2, Chloride, Glucose, Potassium, Sodium, Urea Nitrogen, Phosphorus, Triglycerides, Cholesterol, and Anion Gap	Blood samples were collected to analyze the chemistry parameters: calcium, CO2, chloride, glucose, potassium, sodium, urea nitrogen, phosphorus, triglycerides, cholesterol, and anion gap. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Absolute Values for Chemistry Parameters: Serum Lipase, Serum Amylase	Blood samples were collected to analyze the chemistry parameters: serum lipase and serum amylase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1), and Days 2, 5, and 7
Secondary	Part 2: Absolute Values for Chemistry Parameters: Serum Lipase, Serum Amylase	Blood samples were collected to analyze the chemistry parameters: serum lipase, serum amylase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Absolute Values of Clinical Chemistry Parameters: Albumin, Globulin and Protein	Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1), and Days 2, 5, and 7
Secondary	Part 2: Absolute Values of Clinical Chemistry Parameters: Albumin, Globulin and Protein	Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Absolute Values of Clinical Chemistry Parameters: Creatinine, Direct Bilirubin, Bilirubin, and Urate	Blood samples were collected to analyze the chemistry parameters: creatinine, direct bilirubin, bilirubin, urate. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1), and Days 2, 5, and 7
Secondary	Part 2: Absolute Values of Clinical Chemistry Parameters: Creatinine, Direct Bilirubin, Bilirubin, and Urate	Blood samples were collected to analyze the chemistry parameters: creatinine, direct bilirubin, bilirubin, and urate. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Change From Baseline in Chemistry Parameters: ALT, ALP, AST, GGT, LDH, CK	Blood samples were collected to analyze the chemistry parameters: ALT, ALP, AST, GGT, LDH, CK. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5, and 7
Secondary	Part 2: Change From Baseline in Chemistry Parameters: ALT, ALP, AST, GGT, LDH, CK	Blood samples were collected to analyze the chemistry parameters: ALT, ALP, AST, GGT, LDH, CK. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Change From Baseline in Clinical Chemistry Parameters: Calcium, CO2, Chloride, Glucose, Potassium, Sodium, Urea Nitrogen, Phosphorus, Triglycerides, Cholesterol, and Anion Gap	Blood samples were collected to analyze the chemistry parameters: calcium, CO2, chloride, glucose, potassium, sodium, urea nitrogen, phosphorus, triglycerides, cholesterol, and anion gap. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5, and 7
Secondary	Part 2: Change From Baseline in Clinical Chemistry Parameters: Calcium, CO2, Chloride, Glucose, Potassium, Sodium, Urea Nitrogen, Phosphorus, Triglycerides, Cholesterol, and Anion Gap	Blood samples were collected to analyze the chemistry parameters: calcium, CO2, chloride, glucose, potassium, sodium, urea nitrogen, phosphorus, triglycerides, cholesterol, and anion gap. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Change From Baseline in Clinical Chemistry Parameters: Lipase and Amylase	Blood samples were collected to analyze the chemistry parameters: lipase and amylase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5, and 7
Secondary	Part 2: Change From Baseline in Clinical Chemistry Parameters: Lipase and Amylase	Blood samples were collected to analyze the chemistry parameters: lipase and amylase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Change From Baseline in Clinical Chemistry Parameters: Albumin, Globulin and Protein	Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5, 7
Secondary	Part 2: Change From Baseline in Clinical Chemistry Parameters: Albumin, Globulin and Protein	Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Change From Baseline in Clinical Chemistry Parameters: Creatinine, Direct Bilirubin, Bilirubin, and Urate	Blood samples were collected to analyze the chemistry parameters: creatinine, direct bilirubin, bilirubin, and urate. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5, and 7
Secondary	Part 2: Change From Baseline in Clinical Chemistry Parameters: Creatinine, Direct Bilirubin, Bilirubin, and Urate	Blood samples were collected to analyze the chemistry parameters: Creatinine, direct bilirubin, bilirubin, and urate. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Absolute Values for Urinalysis Parameter: Specific Gravity	Urine samples were collected to analyze the urinalysis parameter: 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. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5, and 7
Secondary	Part 2 : Absolute Values for Urinalysis Parameter: Specific Gravity	Urine samples were collected to analyze the urinalysis parameter: 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. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Absolute Values for Urinalysis Parameters: Potential of Hydrogen (pH)	Urine samples were collected to analyze the urinalysis parameter: 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. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5, and 7
Secondary	Part 1: Absolute Values for Urinalysis Parameter: Potential of Hydrogen	Urine samples were collected to analyze the urinalysis parameter: 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. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Number of Participants With Urinalysis Dipstick Results: Glucose	Urine samples were collected at indicated time points to analyze parameters including glucose by dipstick. Urinalysis included dipstick urine test which was used to screen for glucose. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose can be read as negative in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5, and 7
Secondary	Part 2: Number of Participants With Urinalysis Dipstick Results: Glucose	Urine samples were collected at indicated time points to analyze parameters including glucose by dipstick. Urinalysis included dipstick urine test which was used to screen for glucose. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine glucose can be read as negative in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Number of Participants With Urinalysis Dipstick Results: Protein	Urine samples were collected at indicated time points to analyze parameters including protein by dipstick. Urinalysis included dipstick urine test which was used to screen for protein. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine protein can be read as negative, and trace in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5, and 7
Secondary	Part 2: Number of Participants With Urinalysis Dipstick Results: Protein	Urine samples were collected at indicated time points to analyze parameters including protein by dipstick. Urinalysis included dipstick urine test which was used to screen for protein. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine protein can be read as negative, and trace in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Number of Participants With Urinalysis Dipstick Results: Occult Blood	Urine samples were collected at indicated time points to analyze parameters including occult blood by dipstick. Urinalysis included dipstick urine test which was used to screen for occult blood. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine occult blood can be read as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5, and 7
Secondary	Part 2: Number of Participants With Urinalysis Dipstick Results: Occult Blood	Urine samples were collected at indicated time points to analyze parameters including occult blood by dipstick. Urinalysis included dipstick urine test which was used to screen for occult blood. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine occult blood can be read as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Number of Participants With Urinalysis Dipstick Results: Ketones	Urine samples were collected at indicated time points to analyze parameters including ketones by dipstick. Urinalysis included dipstick urine test which was used to screen for ketones. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine ketones can be read as negative, trace, 2+ indicating proportional concentrations in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5, and 7
Secondary	Part 2: Number of Participants With Urinalysis Dipstick Results: Ketones	Urine samples were collected at indicated time points to analyze parameters including ketones by dipstick. Urinalysis included dipstick urine test which was used to screen for ketones. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine ketones can be read as negative, trace, 1+, 2+ indicating proportional concentrations in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Number of Participants With Urinalysis Dipstick Results: Bilirubin and Nitrite	Urine samples were collected at indicated time points to analyze parameters including bilirubin and nitrite by dipstick. Urinalysis included dipstick urine test which was used to screen for bilirubin and nitrite. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine bilirubin and nitrite can be read as negative in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5, and 7
Secondary	Part 2: Number of Participants With Urinalysis Dipstick Results: Bilirubin and Nitrite	Urine samples were collected at indicated time points to analyze parameters including bilirubin and nitrite by dipstick. Urinalysis included dipstick urine test which was used to screen for bilirubin and nitrite. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine bilirubin and nitrite can be read as negative in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Number of Participants With Urinalysis Dipstick Results: Leukocyte Esterase	Urine samples were collected at indicated time points to analyze parameters including leukocyte esterase by dipstick. Urinalysis included dipstick urine test which was used to screen for leukocyte esterase. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine leukocyte esterase can be read as negative, trace, 1+ indicating proportional concentrations in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5, and 7
Secondary	Part 2: Number of Participants With Urinalysis Dipstick Results: Leukocyte Esterase	Urine samples were collected at indicated time points to analyze parameters including leukocyte esterase by dipstick. Urinalysis included dipstick urine test which was used to screen for leukocyte esterase. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of urine leukocyte esterase can be read as negative, trace indicating proportional concentrations in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Change From Baseline in Urinalysis Parameter: Specific Gravity	Urine samples were collected to analyze the urinalysis parameter: 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. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5, and 7
Secondary	Part 2: Change From Baseline in Urinalysis Parameter: Specific Gravity	Urine samples were collected to analyze the urinalysis parameter: 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. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Change From Baseline for Urinalysis Parameter: Potential of Hydrogen	Urine samples were collected to analyze the urinalysis parameter: 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. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visit, prior to the first study drug administration in each treatment period. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5, and 7
Secondary	Part 2: Change From Baseline for Urinalysis Parameter: Potential of Hydrogen	Urine samples were collected to analyze the urinalysis parameter: 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. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Days 2, 5 and 7
Secondary	Part 1: Number of Participants With Worst Case Urine Parameter: Glucose Results by Maximum Grade Increase Post-Baseline Relative to Baseline	Urine samples were collected to analyze the urine parameter: glucose. Urinalysis parameters were graded according to Division of Acquired Immune Deficiency Syndrome (DAIDS) grading for severity of laboratory toxicities and clinical adverse events, version 2.1. The grades were grade 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening). Baseline was defined as the last assessment before the first dose of the study treatment. Only those urine parameters with maximum post-Baseline grade increase (Grade 1 to Grade 4) have been presented.	Up to Day 17
Secondary	Part 2: Number of Participants With Worst Case Urine Parameter: Glucose Results by Maximum Grade Increase Post-Baseline Relative to Baseline	Urine samples were collected to analyze the urine parameter: glucose. Urinalysis parameters were graded according to Division of Acquired Immune Deficiency Syndrome (DAIDS) grading for severity of laboratory toxicities and clinical adverse events, version 2.1. The grades were grade 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening). Baseline was defined as the last assessment before the first dose of the study treatment. Only those urine parameters with maximum post-Baseline grade increase (Grade 1 to Grade 4) have been presented.	Up to Day 9
Secondary	Part 1: Number of Participants With Worst Case Urine Parameter: Protein Results by Maximum Grade Increase Post-Baseline Relative to Baseline	Urine samples were collected to analyze the urine parameter: protein. Urinalysis parameters were graded according to Division of Acquired Immune Deficiency Syndrome (DAIDS) grading for severity of laboratory toxicities and clinical adverse events, version 2.1. The grades were grade 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening). Baseline was defined as the last assessment before the first dose of the study treatment. Only those urine parameters with maximum post-Baseline grade increase (Grade 1 to Grade 4) have been presented.	Up to Day 17
Secondary	Part 2: Number of Participants With Worst Case Urine Parameter: Protein Results by Maximum Grade Increase Post-Baseline Relative to Baseline	Urine samples were collected to analyze the urine parameter: protein. Urinalysis parameters were graded according to Division of Acquired Immune Deficiency Syndrome (DAIDS) grading for severity of laboratory toxicities and clinical adverse events, version 2.1. The grades were grade 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening). Baseline was defined as the last assessment before the first dose of the study treatment. Only those urine parameters with maximum post-Baseline grade increase (Grade 1 to Grade 4) have been presented.	Up to Day 9
Secondary	Part 1: Number of Participants With Worst Case Urine Parameter: Erythrocytes Results by Maximum Grade Increase Post-Baseline Relative to Baseline	Urine samples were collected to analyze the urine parameter: erythrocytes. Urinalysis parameters were graded according to Division of Acquired Immune Deficiency Syndrome (DAIDS) grading for severity of laboratory toxicities and clinical adverse events, version 2.1. The grades were grade 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening). Baseline was defined as the last assessment before the first dose of the study treatment. Only those urine parameters with maximum post-Baseline grade increase (Grade 1 to Grade 4) have been presented.	Up to Day 17
Secondary	Part 2: Number of Participants With Worst Case Urine Parameter: Erythrocytes Results by Maximum Grade Increase Post-Baseline Relative to Baseline	Urine samples were collected to analyze the urine parameter: erythrocytes. Urinalysis parameters were graded according to Division of Acquired Immune Deficiency Syndrome (DAIDS) grading for severity of laboratory toxicities and clinical adverse events, version 2.1. The grades were grade 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening). Baseline was defined as the last assessment before the first dose of the study treatment. Only those urine parameters with maximum post-Baseline grade increase (Grade 1 to Grade 4) have been presented.	Up to Day 9
Secondary	Part 1: Absolute Values of Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval and QT Interval Corrected by Fridericia's Formula (QTcF)	Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, and QTcF interval . Twelve lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. Baseline was defined as the average of the triplicate pre-dose assessments within each treatment	Baseline (Day 1, pre-dose), and Day 1: 2, 4, 6 hours, and Day 5
Secondary	Part 2: Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF	Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, and QTcF interval. Twelve lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. Baseline was defined as the average of the triplicate pre-dose assessments within each treatment.	Baseline (Day 1, pre-dose), and Day 1: 2, 4, 6 hours, and Days 5, 7
Secondary	Part 1: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF Interval	Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, QTcF interval. Twelve lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. Baseline was defined as the average of the triplicate pre-dose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day 1, Pre-dose), and Day 1: 2, 4, 6 hours, and Day 5
Secondary	Part 2: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF Interval	Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, QTcF interval. Twelve lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. Baseline was defined as the average of the triplicate pre-dose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day 1, pre-dose), and Day 1: 2, 4, 6 hours, Days 5 and 7
Secondary	Part 1: Absolute Values of Vital Sign Parameters: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)	SBP and DBP were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline is defined as the average of the triplicate predose assessments within each treatment.	Baseline (Day 1, pre-dose), and Day 1: 24, 48, 72 hours, Days 5 and 7
Secondary	Part 2: Absolute Values of Vital Signs: DBP and SBP	SBP and DBP were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the average of the triplicate predose assessments within each treatment.	Baseline (Day 1, pre-dose), and Day 1: 24, 48 hours, Days 5 and 7
Secondary	Part 1: Absolute Values of Vital Signs: Pulse Rate	Pulse rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the average of the triplicate predose assessments within each treatment.	Baseline (Day 1, pre-dose), and Day 1: 24, 48, 72 hours, Days 5 and 7
Secondary	Part 2: Absolute Values of Vital Signs: Pulse Rate	Pulse rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the average of the triplicate predose assessments within each treatment.	Baseline (Day 1, pre-dose), and Day 1: 24, 48 hours, Day 5 and 7
Secondary	Part 1: Absolute Values of Vital Signs: Oral Temperature	Oral temperature were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the average of the triplicate predose assessments within each treatment.	Baseline (Day 1, pre-dose), and Day 1: 24, 48, 72 hours, Days 5, 6 and 7
Secondary	Part 2: Absolute Values of Vital Signs: Oral Temperature	Oral temperature were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the average of the triplicate predose assessments within each treatment.	Baseline (Day 1, pre-dose), and Day 1: 24, 48 hours, Day 5 and 7
Secondary	Part 1: Absolute Values of Vital Signs: Respiratory Rate	Respiratory rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the average of the triplicate predose assessments within each treatment.	Baseline (Day 1, pre-dose), and Day 1: 24, 48, 72 hours, Days 5 and 7
Secondary	Part 2: Absolute Values of Vital Signs: Respiratory Rate	Respiratory rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the average of the triplicate predose assessments within each treatment.	Baseline (Day 1, pre-dose), and Day 1: 24, 48 hours, Days 5, and 7
Secondary	Part 1: Change From Baseline in Vital Signs: DBP and SBP	SBP and DBP were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day 1, pre-dose), and Day 1: 24, 48, 72 hours, Days 5, and 7
Secondary	Part 2: Change From Baseline in Vital Signs: DBP and SBP	SBP and DBP were measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day 1, pre-dose), and Day 1: 24, 48 hours, Days 5, and 7
Secondary	Part 1: Change From Baseline in Vital Signs: Pulse Rate	Pulse rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day 1, pre-dose), and Day 1: 24, 48, 72 hours, Days 5, and 7
Secondary	Part 2: Change From Baseline in Vital Signs: Pulse Rate	Pulse rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day 1, pre-dose), and Day 1: 24, 48 hours, Days 5, and 7
Secondary	Part 1: Change From Baseline in Vital Signs: Oral Temperature	Oral temperature was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day 1, pre-dose), and Day 1: 24, 48, 72 hours, Days 5, 6 and 7
Secondary	Part 2: Change From Baseline in Vital Signs: Oral Temperature	Oral temperature was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day 1, pre-dose), and Day 1: 24, 48 hours, Days 5, 6 and 7
Secondary	Part 1: Change From Baseline in Vital Signs: Respiratory Rate	Respiratory rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day 1, pre-dose), and Day 1: 24, 48 hours, Days 5, and 7
Secondary	Part 2: Change From Baseline in Vital Signs: Respiratory Rate	Respiratory rate was measured in the semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the average of the triplicate predose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day 1, pre-dose), and Day 1: 24, 48 hours, Days 5, and 7