Trial Outcomes & Findings for Bioequivalence Study of Paroxetine and PAXIL Under Fasting Conditions in Healthy Mexican Participants (NCT NCT04311463)
NCT ID: NCT04311463
Last Updated: 2022-01-20
Results Overview
Blood samples were collected at indicated time points for the analysis of Cmax of Paroxetine. PK parameters were analyzed using non-compartmental analysis.
COMPLETED
PHASE1
38 participants
Pre-dose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours post-dose
2022-01-20
Participant Flow
This was a single-dose, randomized, balanced, open-label, two-sequence, two-treatment, two-period, crossover bioequivalence study of Paroxetine tablets 20 milligrams (mg) of GlaxoSmithKline (GSK) Pharmaceuticals S.A, with that of PAXIL (Paroxetine) tablets 20 mg of GSK México S.A. de C.V., in healthy adult male \& female participants under fasting conditions.
Total 38 participants were enrolled in the study across one study center in Mexico.
Participant milestones
| Measure |
Paroxetine 20 mg (A) Followed by Paxil 20 mg (B)
Participants received Paroxetine 20 mg tablet (Test drug A) as a single oral dose in treatment period 1. In treatment period 2, participants received Paxil 20 mg tablet (Reference drug B) as a single oral dose. There was a washout period of atleast 7 days between two treatment periods.
|
Paxil 20 mg (B) Followed by Paroxetine 20 mg (A)
Participants received Paxil 20 mg tablet (Reference drug B) as a single oral dose in treatment period 1. In treatment period 2, participants received Paroxetine 20 mg tablet (Test drug A) as a single oral dose. There was a washout period of atleast 7 days between two treatment periods.
|
|---|---|---|
|
Period 1 (Up to Day 3)
STARTED
|
19
|
19
|
|
Period 1 (Up to Day 3)
COMPLETED
|
18
|
19
|
|
Period 1 (Up to Day 3)
NOT COMPLETED
|
1
|
0
|
|
Washout Period (Up to Day 7)
STARTED
|
18
|
19
|
|
Washout Period (Up to Day 7)
COMPLETED
|
17
|
18
|
|
Washout Period (Up to Day 7)
NOT COMPLETED
|
1
|
1
|
|
Period 2 (Up to Day 3)
STARTED
|
17
|
18
|
|
Period 2 (Up to Day 3)
COMPLETED
|
15
|
17
|
|
Period 2 (Up to Day 3)
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
Paroxetine 20 mg (A) Followed by Paxil 20 mg (B)
Participants received Paroxetine 20 mg tablet (Test drug A) as a single oral dose in treatment period 1. In treatment period 2, participants received Paxil 20 mg tablet (Reference drug B) as a single oral dose. There was a washout period of atleast 7 days between two treatment periods.
|
Paxil 20 mg (B) Followed by Paroxetine 20 mg (A)
Participants received Paxil 20 mg tablet (Reference drug B) as a single oral dose in treatment period 1. In treatment period 2, participants received Paroxetine 20 mg tablet (Test drug A) as a single oral dose. There was a washout period of atleast 7 days between two treatment periods.
|
|---|---|---|
|
Period 1 (Up to Day 3)
Participant met Protocol defined withdrawal criteria
|
1
|
0
|
|
Washout Period (Up to Day 7)
Withdrawal by Subject
|
1
|
1
|
|
Period 2 (Up to Day 3)
Participant met Protocol defined withdrawal criteria
|
2
|
1
|
Baseline Characteristics
Bioequivalence Study of Paroxetine and PAXIL Under Fasting Conditions in Healthy Mexican Participants
Baseline characteristics by cohort
| Measure |
Paxil 20 mg (B) Followed by Paroxetine 20 mg (A)
n=19 Participants
Participants received Paxil 20 mg tablet (Reference drug B) as a single oral dose in treatment period 1. In treatment period 2, participants received Paroxetine 20 mg tablet (Test drug A) as a single oral dose. There was a washout period of atleast 7 days between two treatment periods.
|
Total
n=38 Participants
Total of all reporting groups
|
Paroxetine 20 mg (A) Followed by Paxil 20 mg (B)
n=19 Participants
Participants received Paroxetine 20 mg tablet (Test drug A) as a single oral dose in treatment period 1. In treatment period 2, participants received Paxil 20 mg tablet (Reference drug B) as a single oral dose. There was a washout period of atleast 7 days between two treatment periods.
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
19 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
19 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
10 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
19 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
19 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours post-dosePopulation: Pharmacokinetic (PK) analysis set included participants who completed both period of the study as per protocol criteria. Only those participants with data available at the specified data points were analyzed.
Blood samples were collected at indicated time points for the analysis of Cmax of Paroxetine. PK parameters were analyzed using non-compartmental analysis.
Outcome measures
| Measure |
Paroxetine 20 mg (Test A)
n=31 Participants
Participants received Paroxetine 20 mg (Test A) as a single oral dose in fasting condition in Periods 1 and 2
|
Paroxetine 20 mg (Reference B)
n=31 Participants
Participants received Paxil (Paroxetine) 20 mg (Reference B) as a single oral dose in fasting condition in Periods 1 and 2.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Paroxetine
|
8.39 Nanograms per milliliter
Standard Deviation 5.872
|
8.83 Nanograms per milliliter
Standard Deviation 6.554
|
PRIMARY outcome
Timeframe: Pre-dose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours post-dosePopulation: PK analysis set. Only those participants with data available at the specified data points were analyzed.
Blood samples were collected at indicated time points for the analysis of AUC(0-t) of Paroxetine. PK parameters were analyzed using non-compartmental analysis.
Outcome measures
| Measure |
Paroxetine 20 mg (Test A)
n=31 Participants
Participants received Paroxetine 20 mg (Test A) as a single oral dose in fasting condition in Periods 1 and 2
|
Paroxetine 20 mg (Reference B)
n=30 Participants
Participants received Paxil (Paroxetine) 20 mg (Reference B) as a single oral dose in fasting condition in Periods 1 and 2.
|
|---|---|---|
|
Area Under the Concentration-time Curve (AUC) From Time Zero to the Last Measurable Concentration (AUC[0-t]) of Paroxetine
|
128.876 Hour*nanograms per milliliter
Standard Deviation 118.288
|
150.549 Hour*nanograms per milliliter
Standard Deviation 137.497
|
PRIMARY outcome
Timeframe: Pre-dose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours post-dosePopulation: PK analysis set. Only those participants with data available at the specified data points were analyzed.
Blood samples were collected at indicated time points for the analysis of AUC(0-inf) of Paroxetine. PK parameters were analyzed using non-compartmental analysis.
Outcome measures
| Measure |
Paroxetine 20 mg (Test A)
n=31 Participants
Participants received Paroxetine 20 mg (Test A) as a single oral dose in fasting condition in Periods 1 and 2
|
Paroxetine 20 mg (Reference B)
n=30 Participants
Participants received Paxil (Paroxetine) 20 mg (Reference B) as a single oral dose in fasting condition in Periods 1 and 2.
|
|---|---|---|
|
Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of Paroxetine
|
142.482 Hour*nanograms per milliliter
Standard Deviation 149.098
|
160.143 Hour*nanograms per milliliter
Standard Deviation 149.403
|
PRIMARY outcome
Timeframe: Pre-dose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours post-dosePopulation: PK analysis set. Only those participants with data available at the specified data points were analyzed.
Blood samples were collected at indicated time points for the analysis of %AUCex of Paroxetine. PK parameters were analyzed using non-compartmental analysis.
Outcome measures
| Measure |
Paroxetine 20 mg (Test A)
n=31 Participants
Participants received Paroxetine 20 mg (Test A) as a single oral dose in fasting condition in Periods 1 and 2
|
Paroxetine 20 mg (Reference B)
n=30 Participants
Participants received Paxil (Paroxetine) 20 mg (Reference B) as a single oral dose in fasting condition in Periods 1 and 2.
|
|---|---|---|
|
Percentage of AUC (0 to Infinity) Obtained by Extrapolation (%AUCex) of Paroxetine
|
7.95 Percentage of AUCex
Standard Deviation 8.053
|
7.05 Percentage of AUCex
Standard Deviation 7.499
|
PRIMARY outcome
Timeframe: Pre-dose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours post-dosePopulation: PK analysis set. Only those participants with data available at the specified data points were analyzed.
Blood samples were collected at indicated time points for the analysis of Tmax of Paroxetine. PK parameters were analyzed using non-compartmental analysis.
Outcome measures
| Measure |
Paroxetine 20 mg (Test A)
n=31 Participants
Participants received Paroxetine 20 mg (Test A) as a single oral dose in fasting condition in Periods 1 and 2
|
Paroxetine 20 mg (Reference B)
n=31 Participants
Participants received Paxil (Paroxetine) 20 mg (Reference B) as a single oral dose in fasting condition in Periods 1 and 2.
|
|---|---|---|
|
Time of the Maximum Measured Plasma Concentration (Tmax) of Paroxetine
|
5.00 Hours
Interval 1.5 to 8.0
|
5.00 Hours
Interval 0.0 to 8.0
|
PRIMARY outcome
Timeframe: Pre-dose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours post-dosePopulation: PK analysis set. Only those participants with data available at the specified data points were analyzed.
Blood samples were collected at indicated time points for the analysis of t1/2 of Paroxetine. PK parameters were analyzed using non-compartmental analysis.
Outcome measures
| Measure |
Paroxetine 20 mg (Test A)
n=31 Participants
Participants received Paroxetine 20 mg (Test A) as a single oral dose in fasting condition in Periods 1 and 2
|
Paroxetine 20 mg (Reference B)
n=30 Participants
Participants received Paxil (Paroxetine) 20 mg (Reference B) as a single oral dose in fasting condition in Periods 1 and 2.
|
|---|---|---|
|
Elimination Half-life (t1/2) of Paroxetine
|
10.78 Hours
Interval 4.19 to 21.46
|
11.32 Hours
Interval 7.96 to 21.32
|
PRIMARY outcome
Timeframe: Pre-dose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours post-dosePopulation: PK analysis set. Only those participants with data available at the specified data points were analyzed.
Blood samples were collected at indicated time points for the analysis of Kel of Paroxetine. PK parameters were analyzed using non-compartmental analysis.
Outcome measures
| Measure |
Paroxetine 20 mg (Test A)
n=31 Participants
Participants received Paroxetine 20 mg (Test A) as a single oral dose in fasting condition in Periods 1 and 2
|
Paroxetine 20 mg (Reference B)
n=30 Participants
Participants received Paxil (Paroxetine) 20 mg (Reference B) as a single oral dose in fasting condition in Periods 1 and 2.
|
|---|---|---|
|
Terminal Elimination Rate Constant (Kel) of Paroxetine
|
0.0653 Per hour
Standard Deviation 0.02152
|
0.0618 Per hour
Standard Deviation 0.01331
|
SECONDARY outcome
Timeframe: Up to 25 daysPopulation: Safety analysis set included all participants who received at least one dose of study treatment.
An adverse event (AE) is any untoward medical occurrence that may occur in a research participant during clinical research phase of a drug or vaccine but which does not necessarily has a causal relationship with this. SAE is defined as any medical occurrence that, at any dose, put participants's life in risk or results in death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent significant disability/incapacity, is a congenital anomaly/birth defect and other important medical events according to medical or scientific judgement.
Outcome measures
| Measure |
Paroxetine 20 mg (Test A)
n=38 Participants
Participants received Paroxetine 20 mg (Test A) as a single oral dose in fasting condition in Periods 1 and 2
|
Paroxetine 20 mg (Reference B)
n=38 Participants
Participants received Paxil (Paroxetine) 20 mg (Reference B) as a single oral dose in fasting condition in Periods 1 and 2.
|
|---|---|---|
|
Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)
Non-serious AEs
|
7 Participants
|
7 Participants
|
|
Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)
SAEs
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 25 daysPopulation: Safety analysis set.
Systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate, respiration rate and body temperature were measured in semi-supine position after 5 minutes rest. The clinically acceptable range included; SBP: 85 millimeters of mercury (mmHg) to 160 mmHg; DBP: 45 mmHg to 100 mmHg; pulse rate: 40 beats per minute to 110 beats per minute; respiration rate: 8 breaths per minute to 20 breaths per minute; body temperature: 35.5 degrees Celsius to 37.8 degrees Celsius. Number of participants with any abnormality in vital signs are presented. Data is presented treatment wise.
Outcome measures
| Measure |
Paroxetine 20 mg (Test A)
n=38 Participants
Participants received Paroxetine 20 mg (Test A) as a single oral dose in fasting condition in Periods 1 and 2
|
Paroxetine 20 mg (Reference B)
n=38 Participants
Participants received Paxil (Paroxetine) 20 mg (Reference B) as a single oral dose in fasting condition in Periods 1 and 2.
|
|---|---|---|
|
Number of Participants With Abnormal Vital Signs
|
0 Participants
|
0 Participants
|
Adverse Events
Paroxetine 20 mg (Test A)
Paroxetine 20 mg (Reference B)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Paroxetine 20 mg (Test A)
n=38 participants at risk
Participants received Paroxetine 20 mg (Test A) as a single oral dose in fasting condition in Periods 1 and 2.
|
Paroxetine 20 mg (Reference B)
n=38 participants at risk
Participants received Paxil (Paroxetine) 20 mg (Reference B) as a single oral dose in fasting condition in Periods 1 and 2.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
5.3%
2/38 • Number of events 2 • All-cause mortality, non-serious AEs and Serious AEs were collected up to 25 days
All-cause mortality, non-serious AEs and SAEs were collected in safety analysis set. Safety analysis set included all participants who received at least one dose of study treatment.
|
2.6%
1/38 • Number of events 1 • All-cause mortality, non-serious AEs and Serious AEs were collected up to 25 days
All-cause mortality, non-serious AEs and SAEs were collected in safety analysis set. Safety analysis set included all participants who received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Dyspepsia
|
2.6%
1/38 • Number of events 1 • All-cause mortality, non-serious AEs and Serious AEs were collected up to 25 days
All-cause mortality, non-serious AEs and SAEs were collected in safety analysis set. Safety analysis set included all participants who received at least one dose of study treatment.
|
2.6%
1/38 • Number of events 1 • All-cause mortality, non-serious AEs and Serious AEs were collected up to 25 days
All-cause mortality, non-serious AEs and SAEs were collected in safety analysis set. Safety analysis set included all participants who received at least one dose of study treatment.
|
|
Nervous system disorders
Nausea
|
7.9%
3/38 • Number of events 3 • All-cause mortality, non-serious AEs and Serious AEs were collected up to 25 days
All-cause mortality, non-serious AEs and SAEs were collected in safety analysis set. Safety analysis set included all participants who received at least one dose of study treatment.
|
10.5%
4/38 • Number of events 5 • All-cause mortality, non-serious AEs and Serious AEs were collected up to 25 days
All-cause mortality, non-serious AEs and SAEs were collected in safety analysis set. Safety analysis set included all participants who received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Odynophagia
|
2.6%
1/38 • Number of events 1 • All-cause mortality, non-serious AEs and Serious AEs were collected up to 25 days
All-cause mortality, non-serious AEs and SAEs were collected in safety analysis set. Safety analysis set included all participants who received at least one dose of study treatment.
|
2.6%
1/38 • Number of events 1 • All-cause mortality, non-serious AEs and Serious AEs were collected up to 25 days
All-cause mortality, non-serious AEs and SAEs were collected in safety analysis set. Safety analysis set included all participants who received at least one dose of study treatment.
|
|
Gastrointestinal disorders
Vomiting
|
2.6%
1/38 • Number of events 1 • All-cause mortality, non-serious AEs and Serious AEs were collected up to 25 days
All-cause mortality, non-serious AEs and SAEs were collected in safety analysis set. Safety analysis set included all participants who received at least one dose of study treatment.
|
0.00%
0/38 • All-cause mortality, non-serious AEs and Serious AEs were collected up to 25 days
All-cause mortality, non-serious AEs and SAEs were collected in safety analysis set. Safety analysis set included all participants who received at least one dose of study treatment.
|
|
Nervous system disorders
Headache
|
10.5%
4/38 • Number of events 5 • All-cause mortality, non-serious AEs and Serious AEs were collected up to 25 days
All-cause mortality, non-serious AEs and SAEs were collected in safety analysis set. Safety analysis set included all participants who received at least one dose of study treatment.
|
13.2%
5/38 • Number of events 5 • All-cause mortality, non-serious AEs and Serious AEs were collected up to 25 days
All-cause mortality, non-serious AEs and SAEs were collected in safety analysis set. Safety analysis set included all participants who received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
2.6%
1/38 • Number of events 1 • All-cause mortality, non-serious AEs and Serious AEs were collected up to 25 days
All-cause mortality, non-serious AEs and SAEs were collected in safety analysis set. Safety analysis set included all participants who received at least one dose of study treatment.
|
0.00%
0/38 • All-cause mortality, non-serious AEs and Serious AEs were collected up to 25 days
All-cause mortality, non-serious AEs and SAEs were collected in safety analysis set. Safety analysis set included all participants who received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
|
2.6%
1/38 • Number of events 1 • All-cause mortality, non-serious AEs and Serious AEs were collected up to 25 days
All-cause mortality, non-serious AEs and SAEs were collected in safety analysis set. Safety analysis set included all participants who received at least one dose of study treatment.
|
0.00%
0/38 • All-cause mortality, non-serious AEs and Serious AEs were collected up to 25 days
All-cause mortality, non-serious AEs and SAEs were collected in safety analysis set. Safety analysis set included all participants who received at least one dose of study treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial
- Publication restrictions are in place
Restriction type: OTHER