Bioequivalence Study of Paroxetine Immediate Release (IR) Tablets Manufactured in GlaxoSmithKline Tianjin (GSKT) and Mississauga Sites in Healthy Chinese Subjects

Anxiety Disorders Clinical Trial

Official title:

Randomized, Open Label, 2-way Crossover, Single Dose Bioequivalence Study of Paroxetine IR Tablets Manufactured in GSKT and Mississauga Sites in Healthy Chinese Participants Under Fasting and Fed Conditions

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03329573
• Other study ID #: 207652
• Status: Completed
• Phase: Phase 1
• Start date: May 30, 2018
• Est. completion date: August 3, 2018

Study information

• Verified date: March 2020
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) and paroxetine IR tablets have been approved for the treatment of three anxiety indications in China. This bioequivalence study will evaluate Paroxetine IR tablets manufactured in GSKT (A) and Mississauga (B) sites in healthy Chinese subjects under fasting and fed conditions to support the quality consistency evaluation. This is a single dose, open-label, randomized, two-period crossover study and will include a screening period (up to 7 days), two open-label treatment periods (up to 16 days) and a follow-up phase (up to 14 days after last-dose). The whole study will be divided into two groups, one for fasting condition enrolling approximately 36 subjects and another for fed condition for which approximately 44 subjects will be enrolled. In both groups, eligible subjects will be randomized to receive single dose of Paroxetine IR tablets A or B in a cross-over manner.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: August 3, 2018
• Est. primary completion date: August 3, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Able to actively communicate with the investigator and to complete the study-related documents; able to understand the contents of the Informed consent form (ICF) and to sign a written ICF prior to any study-specific procedures.

• Males and females aged between 18 and 45 years inclusive, at the time of signing the informed consent.

• Non-smoking healthy males and females as assessed by medical history and physical examination. Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters which are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator (in consultation with the GSK Medical Monitor if necessary) agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.

• Body weight>=50 kilograms (kg) (male) or 45kg(female) and Body mass index (BMI) 19.0 to 26.0 kg per meter square (kg/m^2) (inclusive).

• A female subject is eligible to participate if she is of: Child-bearing potential with negative pregnancy test as determined by serum or urine human chorionic gonadotropin (hCG) test at screening or prior to dosing and agrees to use the one of the defined contraception method during the study and until follow up contact.

• Male Subjects with female partners of child-bearing potential must agree to use one of the defined contraception methods during the study and until follow up contact.

• ALT, ALP and total bilirubin <=1.5x upper limit of normal (ULN) (isolated bilirubin >1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).

• Based on single or averaged corrected QT interval (QTc) values of triplicate ECGs obtained over a brief recording period: QTc < 450 milliseconds (msec); or QTc < 480 msec in subjects with bundlebranch block.

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).

• Drug or alcohol abuse or dependency within one year prior to enrolment. History of regular alcohol consumption within one year of the study defined as: an average weekly intake of >14 drinks. One drink is equivalent to 12 grams (g) of alcohol: 12 ounces [360 milliliter (mL)] of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.

• Unstable disease conditions; any laboratory measurements assessed by the investigator as clinically relevant (including ECG, hematology, biochemistry and urine analysis, etc.);any disorder that might interfere with the absorption, distribution, metabolism or excretion of the study drug; or in the investigator's opinion the disease may lead to safety concerns or interfere with the pharmacokinetics assessment.

• Subjects with concurrent or previous neuropsychological disorders, as assessed by Columbia Suicide Severity Rating Scale or by the investigator, have suicidal tendency, or have committed suicidal behavior/attempt.

• Known history of cerebral trauma, previous cerebral disorders, seizures or eating disorder, and other conditions that in the investigator's opinion may increase the risk of seizures.

• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

• Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study medication.

• In subjects with concomitant use of monoamine oxidase inhibitors (MAOIs) (including linezolid, an antibiotic which is a reversible non-selective MAOIs and methylthioninium chloride (methylene blue)) or within two weeks of terminating treatment with MAOIs.

• In subjects with concomitant use of thioridazine or pimozide.

• The subject has participated in a clinical trial and has received an investigational product within 90 days prior to the first dosing day in the current study, or has participated in a clinical trial without receiving any investigational product within 30 days prior to the first dosing day in the current study.

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months.

• Serum human immuno-deficiency virus (HIV) antibody or Syphilis antibody positive.

• A positive pre-study drug/alcohol screen.

• Known allergy to paroxetine IR Tablets or any of its components.

• Blood donation in excess of 400 mL in the 3 months prior to enrolment.

• Obvious evidence of active hematological diseases, or significant blood loss in the last 3 months. History of sensitivity to heparin or heparin-induced thrombocytopenia.

• Lactating females or women of child bearing potential used oral or implanted contraceptives within the 30 days prior to enrolment, or received injections of chronically acting contraceptives in the 1 year prior to study initiation.

• Other conditions which, in the Investigator's judgment, render subjects unsuitable for the clinical study.

Related Conditions & MeSH terms

• Anxiety Disorders

Intervention

Drug:
• Paroxetine IR tablets A
Paroxetine IR tablets A will be the investigational drug. These are film coated tablets with unit dose strength of 20 milligrams (mg) and will be administered via oral route. These tablets will be manufactured in GSKT.
• Paroxetine IR tablets B
Paroxetine IR tablets B will be the reference drug. These are film coated tablets with unit dose strength of 20 mg and will be administered via oral route. These tablets will be manufactured in Mississauga.

Locations

Country	Name	City	State
China	GSK Investigational Site	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC[0-infinity]) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition	Blood samples were collected at designated time points. Pharmacokinetic (PK) parameters of Paroxetine were calculated using non-compartmental methods. Statistical analysis of PK parameters was done using mixed effect model for evaluation of bioequivalence (BE). Point estimate and associated adjusted 90% confidence interval (CI) of difference between both the treatments were provided for AUC(0-infinity).	Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
Primary	AUC(0-infinity) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition	Blood samples were collected at designated timepoints. PK parameters of Paroxetine were calculated using non-compartmental methods. Statistical analysis of PK parameters was done using mixed effect model for evaluation of BE. Point estimate and associated adjusted 90% CI of difference between both the treatments were provided for AUC(0-infinity).	Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
Primary	Area Under the Concentration-time Curve From Administration Extrapolated to the Last Time of Quantifiable Concentration (AUC[0-t]) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition	Blood samples were collected at designated timepoints. PK parameters of Paroxetine were calculated using non-compartmental methods. Statistical analysis of PK parameters was done using mixed effect model for evaluation of BE. Point estimate and associated adjusted 90% CI of difference between both the treatments were provided for AUC(0-t).	Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
Primary	AUC(0-t) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition	Blood samples were collected at designated timepoints. PK parameters of Paroxetine were calculated using non-compartmental methods. Statistical analysis of PK parameters was done using mixed effect model for evaluation of BE. Point estimate and associated adjusted 90% CI of difference between both the treatments were provided for AUC(0-t).	Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
Primary	Maximum Observed Concentration (Cmax) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition	Blood samples were collected at designated timepoints. PK parameters of Paroxetine were calculated using non-compartmental methods. Statistical analysis of PK parameters was done using mixed effect model for evaluation of BE. Point estimate and associated adjusted 90% CI of difference between both the treatments were provided for Cmax.	Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
Primary	Cmax of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition	Blood samples were collected at designated timepoints. PK parameters of Paroxetine were calculated using non-compartmental methods. Statistical analysis of PK parameters was done using mixed effect model for evaluation of BE. Point estimate and associated adjusted 90% CI of difference between both the treatments were provided for Cmax.	Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
Secondary	Time to Reach Maximum Observed Concentration (Tmax) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition	Blood samples were collected at designated timepoints. PK parameters of Paroxetine were calculated using non-compartmental methods. Median and full range of Tmax have been presented.	Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
Secondary	Tmax of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition	Blood samples were collected at designated timepoints. PK parameters of Paroxetine were calculated using non-compartmental methods. Median and full range of Tmax have been presented.	Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
Secondary	Terminal Elimination Rate Constant (Lambda z) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition	Blood samples were collected at designated timepoints. PK parameters of Paroxetine were calculated using non-compartmental methods. Geometric mean and 95% CI of Lambda z have been presented.	Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
Secondary	Lambda z of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition	Blood samples were collected at designated timepoints. PK parameters of Paroxetine were calculated using non-compartmental methods. Geometric mean and 95% CI of Lambda z have been presented.	Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
Secondary	Terminal Elimination Half-life (t1/2) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition	Blood samples were collected at designated timepoints. PK parameters of Paroxetine were calculated using non-compartmental methods. Geometric mean and 95% CI have been presented.	Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
Secondary	t1/2 of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition	Blood samples were collected at designated timepoints. PK parameters of Paroxetine were calculated using non-compartmental methods. Geometric mean and 95% CI have been presented.	Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
Secondary	Number of Participants With Non-serious Adverse Events and Serious Adverse Events (SAEs) Under Fed Condition	An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect and other situations according to medical or scientific judgement or events associated with liver injury and impaired liver function. Data has been presented treatment-wise.	Up to Day 26
Secondary	Number of Participants With Non-SAE and SAEs Under Fasting Condition	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect and other situations according to medical or scientific judgement or events associated with liver injury and impaired liver function. Data has been presented treatment-wise.	Up to Day 26
Secondary	Number of Participants With Chemistry Laboratory Values Relative to Potential Clinical Importance (PCI) Criteria on Day 16 Under Fed Condition	Blood samples were collected to analyze the clinical chemistry laboratory parameters; alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST),calcium,creatinine, glucose, potassium (Pot) and sodium. PCI ranges were ALT (high: >=2 times upper limit of normal [ULN] units per liter [U/L]),albumin (low: <30 grams per liter),ALP (low: <20 international units per liter [IU/L] and high: >200 IU/L), AST (high: >=2 times ULN U/L),calcium (low: <2 millimoles per liter [mmol/L] and high: >2.75 mmol/L),creatinine (high: >133 micromoles per liter), glucose (low: <3 mmol/L and high: >9 mmol/L), Pot (low: <3 mmol/L and high: >5.5 mmol/L) and sodium (low: <130 mmol/L and high: >150 mmol/L). Participants were counted in the category that their value changed to (low, normal or high). If values were unchanged (example: High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Data has been presented treatment-wise.	Day 16
Secondary	Number of Participants With Chemistry Laboratory Values Relative to PCI Criteria on Day 16 Under Fasting Condition	Blood samples were collected to analyze the clinical chemistry laboratory parameters; ALT, albumin, ALP, AST, calcium, creatinine, glucose, Pot and sodium. PCI ranges were ALT (high: >=2 times ULN U/L), albumin (low: <30 grams per liter), ALP (low: <20 IU/L and high: >200 IU/L), AST (high: >=2 times ULN U/L), calcium (low: <2 mmol/L and high: >2.75 mmol/L), creatinine (high: >133 micromoles per liter), glucose (low: <3 mmol/L and high: >9 mmol/L), Pot (low: <3 mmol/L and high: >5.5 mmol/L) and sodium (low: <130 mmol/L and high: >150 mmol/L). Participants were counted in the category that their value changed to (low, normal or high). If values were unchanged (example: High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Data has been presented treatment-wise.	Day 16
Secondary	Number of Participants With Hematology Laboratory Values Relative to PCI Criteria on Day 16 Under Fed Condition	Blood samples were collected to analyze; hematocrit(Hct),hemoglobin(Hb),erythrocytes and platelets. PCI ranges; Hct(Male[low: <0.03 proportion of red blood cells in blood and high: >0.54 proportion of red blood cells in blood] and Female[low: <0.04 proportion of red blood cells in blood and high: >0.54 proportion of red blood cells in blood]),Hb(Male [low: <110 grams per liter and high: >180 grams per liter) and Female[low: <100 grams per liter and high: >170 grams per liter]),erythrocytes(Male [low: <4.5x10^12 cells per liter and high: >5.5x10^12 cells per liter] and Female[low: <4 x10^12 cells per liter and high: >5 x10^12 cells per liter]) and platelets(low: <80x10^9 cells per liter and high: >400x10^9 cells per liter). Participants were counted in the category that their value changed to(low, normal or high). If values were unchanged(example: High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category.Data has been presented treatment-wise.	Day 16
Secondary	Number of Participants With Hematology Laboratory Values Relative to PCI Criteria on Day 16 Under Fasting Condition	Blood samples were collected to analyze; Hct, Hb, erythrocytes and platelets. PCI ranges were Hct (Male [low: <0.03 proportion of red blood cells in blood and high: >0.54 proportion of red blood cells in blood] and Female [low: <0.04 proportion of red blood cells in blood and high: >0.54 proportion of red blood cells in blood]), Hb (Male [low: <110 grams per liter and high: >180 grams per liter) and Female [low: <100 grams per liter and high: >170 grams per liter]), erythrocytes (Male [low: <4.5x10^12 cells per liter and high: >5.5x10^12 cells per liter] and Female [low: <4 x10^12 cells per liter and high: >5 x10^12 cells per liter]) and platelets (low: <80x10^9 cells per liter and high: >400x10^9 cells per liter). Participants were counted in the category that their value changed to (low, normal or high). If values were unchanged (example: High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Data has been presented treatment-wise.	Day 16
Secondary	Number of Participants With Urinalysis Results by Dipstick Method Under Fed Condition	Urine samples were collected to assess urine occult blood, urine glucose, urine ketones, urine protein and monitor urine potential of hydrogen (pH). The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters (except urine pH) were recorded as negative and positive, indicating proportional concentrations in the urine sample. pH is a measure of hydrogen ion concentration and is used to determine the acidity or alkalinity of urine. Urine pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH of less than 7 is acidic and a pH of greater than 7 is basic. Normal urine has a slightly acidic pH (5.0-6.0). Dipstick test results for pH were presented as number of participants having pH value as 5, 6, 6.5, 7 or 8. Data has been presented treatment-wise.	Baseline (Day-7 to Day -1) and Day 16
Secondary	Number of Participants With Urinalysis Results by Dipstick Method Under Fasting Condition	Urine samples were collected to assess urine occult blood, urine glucose, urine ketones, urine protein and monitor urine pH. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters (except urine pH) were recorded as negative and positive, indicating proportional concentrations in the urine sample. pH is a measure of hydrogen ion concentration and is used to determine the acidity or alkalinity of urine. Urine pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH of less than 7 is acidic and a pH of greater than 7 is basic. Normal urine has a slightly acidic pH (5.0-6.0). Dipstick test results for pH were presented as number of participants having pH value as 5, 6, 6.5, 7 or 8. Data has been presented treatment-wise.	Baseline (Day-7 to Day -1) and Day 16
Secondary	Number of Participants With Clinically Significant Abnormal Findings for Electrocardiogram (ECG) Parameters Under Fed Condition	A single 12-lead ECGs was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QT corrected (QTc) intervals. Clinically significant abnormal ranges were: heart rate: lower:<50 beats per minute and upper: >110 beats per minute; QT: Upper: >400 milliseconds (msec); QTc: Upper: >450 msec; PR: lower: <110 msec and upper: >220 msec; QRS: lower: <60 msec and upper: >120 msec. The number of participants with abnormal findings for ECG parameters have been presented. Data has been presented treatment-wise.	Baseline (Day-7 to Day -1) and Day 16
Secondary	Number of Participants With Clinically Significant Abnormal Findings for ECG Parameters Under Fasting Condition	A single 12-lead ECGs was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTc intervals. Clinically significant abnormal ranges were: heart rate: lower :<50 beats per minute and upper: >110 beats per minute; QT: Upper: >400 msec; QTc: Upper: >450 msec; PR: lower: <110 msec and upper: >220 msec; QRS: lower: <60 msec and upper: >120 msec. The number of participants with abnormal findings for ECG parameters have been presented. Data has been presented treatment-wise.	Baseline (Day-7 to Day -1) and Day 16
Secondary	Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) at Indicated Time-points Under Fed Condition	Vital signs including DBP and SBP were measured at the indicated time-points and summarized during the study to evaluate the safety of the participants. Data has been presented treatment-wise.	Day 1 (post-dose), Day 2 (post-dose), Day 3, Day 4, Day 5, Day 11, Day 12 (pre-dose), Day 12 (post-dose), Day 13 (post-dose), Day 14, Day 15, Day 16
Secondary	DBP and SBP at Indicated Time-points Under Fasting Condition	Vital signs including DBP and SBP were measured at the indicated time-points and summarized during the study to evaluate the safety of the participants. Data has been presented treatment-wise.	Day 1 (post-dose), Day 2 (post-dose), Day 3, Day 4, Day 5, Day 11, Day 12 (pre-dose), Day 12 (post-dose), Day 13 (post-dose), Day 14, Day 15, Day 16
Secondary	Pulse Rate (PR) at Indicated Time-points Under Fed Condition	Vital sign including PR was measured at the indicated time-points and summarized during the study to evaluate the safety of the participants. Data has been presented treatment-wise.	Day 1 (post-dose), Day 2 (post-dose), Day 3, Day 4, Day 5, Day 11, Day 12 (pre-dose), Day 12 (post-dose), Day 13 (post-dose), Day 14, Day 15, Day 16
Secondary	Pulse Rate (PR) at Indicated Time-points Under Fasting Condition	Vital sign including PR was measured at the indicated time-points and summarized during the study to evaluate the safety of the participants. Data has been presented treatment-wise.	Day 1 (post-dose), Day 2 (post-dose), Day 3, Day 4, Day 5, Day 11, Day 12 (pre-dose), Day 12 (post-dose), Day 13 (post-dose), Day 14, Day 15, Day 16
Secondary	Respiratory Rate (RR) at Indicated Time-point Under Fed Condition	Vital sign including RR was measured at the indicated time-point and summarized during the study to evaluate the safety of the participants. Data has been presented treatment-wise.	Day 11
Secondary	RR at Indicated Time-point Under Fasting Condition	Vital sign including RR was measured at the indicated time-point and summarized during the study to evaluate the safety of the participants. Data has been presented treatment-wise.	Day 11
Secondary	Temperature at Indicated Time-point Under Fed Condition	Vital sign including temperature was measured at the indicated time-point and summarized during the study to evaluate the safety of the participants. Data has been presented treatment-wise.	Day 11
Secondary	Temperature at Indicated Time-point Under Fasting Condition	Vital sign including temperature was measured at the indicated time-point and summarized during the study to evaluate the safety of the participants. Data has been presented treatment-wise.	Day 11