Depressive Disorder
Conditions
Keywords
Bioequivalence, Paroxetine reference/test, healthy volunteers, Fed condition
Brief summary
The study is prospective, open, randomized, crossover in steady state and the volunteers received multiple doses of the test drug and the reference drug (two periods of drug administration after standardized meals).
Detailed description
Title: Relative bioavailability study between the formulations: Paroxetine Hydrochloride 25 mg tablet with controlled release (Paxil CR) manufactured by GlaxoSmithKline Inc. - Mississauga - Canada (test formulation) and Paroxetine Hydrochloride 25 mg tablets with controlled release (Paxil CR) manufactured by SmithKline Beecham (Cork) Limited - Cidra - Puerto Rico (reference formulation), fed administration in healthy volunteers of both genders. The study is prospective, open, randomized, crossover in steady state and the volunteers received multiple doses of the drug test and reference (two periods of drug administration). The population is composed of 60 healthy volunteers, adult of both gender, with age between 18 and 40 years, with a body mass index (BMI) between 18.5 and 27. Volunteers have weight above than 50 kg. 50% of the volunteers recruited are female and 50% male. There are no restrictions regarding the ethnic group. The relative bioavailability of the formulations after oral administration in steady state will be evaluated based on statistical comparisons of relevant pharmacokinetic parameters obtained from data of drug concentration in blood. The concentration of Paroxetine hydrochloride (controlled release) will be measured by an appropriate analytical method and valid after the drug administration.The Pharmacokinetic samples will be collected at steady state in each period after standardized meals. The safety assessment will include evaluation and clinical monitoring, vital signs monitoring, ECG, and laboratory tests. Adverse events will be monitored throughout the study.
Interventions
DRUGPaxil CR 25 mg manufactured by SmithKline Beecham (Cork) Limited - Cidra - Puerto Rico
Paroxetine Hydrochloride 25 miligrams(mg) tablet with controlled release (Paxil CR), once a day, manufactured by SmithKline Beecham (Cork) Limited - Cidra - Puerto Rico (reference formulation)
DRUGPaxil CR 25 mg manufactured by GlaxoSmithKline Inc. - Mississauga - Canada
Paroxetine Hydrochloride 25 mg tablet with controlled release (Paxil CR), once a day, manufactured by GlaxoSmithKline Inc. - Mississauga - Canada (test formulation)
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Exclusion criteria
* hypersensitivity to the study drug or to compounds chemically related; * history of serious adverse events; * concurrent or recent use of other antidepressives, schizophrenia, anticonvulsant; * History of liver, heart, gastrointestinal or renal illness; * ECG findings not recommended according to the investigator judgement; * The volunteer ingests more than 5 cups of coffee or tea a day. INCLUSION CRITERIA: * Man and woman (since they are not pregnant or breastfeeding); * age between 18 and 40 years; * non-smoker and not addict; * mass index between 18,5 and 27; * good health conditions or without significant illness, by judgement of a legally qualified professional; * sign the informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC_ss | Days 14 to 17 (period 1) and Days 23 to 24 (Period 2) | The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC\_ss is the area under the curve during the steady-state period. The AUC\_ss is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. ng, nanograms; h, hour; ml, milliliter; ng.h/ml, nanograms per hour per milliliter. |
| Cmin_ss | Days 14 to 17 (period 1) and Days 23 to 24 (Period 2) | Cmin\_ss is defined as the minimum concentration of a drug observed after its administration, in steady-state. Cmin\_ss is one of the parameters of particular use in estimating the bioavailability of drugs, for studies employing multiple doses. |
| Cmax_ss | Days 14 to 17 (period 1) and Days 23 to 24 (Period 2) | Cmax\_ss is defined as the maximum or peak concentration of a drug observed after its administration, in steady-state. Cmax\_ss is one of the parameters of particular use in estimating the bioavailability of drugs, by measuring the total amount of drug absorbed. |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants Receiving Both Test and Reference Product Participants receiving either test product: Paxil CR 25 mg manufactured by GlaxoSmithKline Inc. - Mississauga - Canada in Period 1; followed by reference product: Paxil CR 25 mg manufactured by SmithKline Beecham (Cork) Limited - Cidra - Puerto Rico in Period 2 or reference product in Period 1 and test product in Period 2 | 60 |
| Total | 60 |
Baseline characteristics
| Characteristic | Participants Receiving Both Test and Reference Product |
|---|---|
| Age, Continuous | 27.73 Years STANDARD_DEVIATION 4.65 |
| Race/Ethnicity, Customized Black | 4 participants |
| Race/Ethnicity, Customized Caucasian | 35 participants |
| Race/Ethnicity, Customized Mixed Race | 21 participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 48 / 60 | 20 / 60 |
| serious Total, serious adverse events | 0 / 60 | 0 / 60 |
Outcome results
Primary
AUC_ss
The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC\_ss is the area under the curve during the steady-state period. The AUC\_ss is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. ng, nanograms; h, hour; ml, milliliter; ng.h/ml, nanograms per hour per milliliter.
Time frame: Days 14 to 17 (period 1) and Days 23 to 24 (Period 2)
Population: Entire study population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | AUC_ss | 672.9221 ng.h/ml | Standard Deviation 432.2451 |
| Reference Product | AUC_ss | 645.5407 ng.h/ml | Standard Deviation 413.9084 |
90% CI: [1.0011, 1.177]
Primary
Cmax_ss
Cmax\_ss is defined as the maximum or peak concentration of a drug observed after its administration, in steady-state. Cmax\_ss is one of the parameters of particular use in estimating the bioavailability of drugs, by measuring the total amount of drug absorbed.
Time frame: Days 14 to 17 (period 1) and Days 23 to 24 (Period 2)
Population: Entire study population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | Cmax_ss | 36.7235 ng/ml | Standard Deviation 21.0928 |
| Reference Product | Cmax_ss | 36.6630 ng/ml | Standard Deviation 21.9946 |
90% CI: [0.9716, 1.0956]
Primary
Cmin_ss
Cmin\_ss is defined as the minimum concentration of a drug observed after its administration, in steady-state. Cmin\_ss is one of the parameters of particular use in estimating the bioavailability of drugs, for studies employing multiple doses.
Time frame: Days 14 to 17 (period 1) and Days 23 to 24 (Period 2)
Population: Entire study population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | Cmin_ss | 19.4468 ng/ml | Standard Deviation 13.778 |
| Reference Product | Cmin_ss | 18.9010 ng/ml | Standard Deviation 12.6797 |
90% CI: [0.9676, 1.0849]