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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
85
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 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.
GSK Investigational Site
Shanghai, China
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).
Time frame: 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
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).
Time frame: 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
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).
Time frame: 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
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).
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
Terminal Elimination Half-life (t1/2) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition
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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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: Up to Day 26
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.
Time frame: Up to Day 26
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.
Time frame: Day 16
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.
Time frame: Day 16
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.
Time frame: Day 16
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.
Time frame: Day 16
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.
Time frame: Baseline (Day-7 to Day -1) and Day 16
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.
Time frame: Baseline (Day-7 to Day -1) and Day 16
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.
Time frame: Baseline (Day-7 to Day -1) and Day 16
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.
Time frame: Baseline (Day-7 to Day -1) and Day 16
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: Day 11
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.
Time frame: Day 11
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.
Time frame: Day 11
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.
Time frame: Day 11