Paxil CR Bioequivalence Study Brazil - Fed Administration

Study Overview
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Brief Summary
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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
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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.

Official Title
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Relative Bioavailability Study Between the Formulations: Paroxetine 25 mg Tablets With Controlled Release Manufactured by GSK Mississauga and Paroxetine 25 mg Tablets With Controlled Release Manufactured by SmithKline Beecham (Cidra), Fed Administration in Healthy Volunteers of Both Genders

Conditions
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Depressive Disorder

Intervention / Treatment
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* Drug: Paxil CR 25 mg manufactured by SmithKline Beecham (Cork) Limited - Cidra - Puerto Rico
* Drug: Paxil CR 25 mg manufactured by GlaxoSmithKline Inc. - Mississauga - Canada


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Paxil CR Reference<br>Paroxetine Hydrochloride 25 miligrams(mg) tablet with controlled release (Paxil CR), once a day, manufactured by SmithKline Beecham (Cork) Limited - Cidra - Puerto Rico, in Period 1, followed by Paroxetine Hydrochloride 25 mg tablet with controlled release (Paxil CR), once a day, manufactured by GlaxoSmithKline Inc. - Mississauga - Canada, in Period 2 | Drug: Paxil CR 25 mg manufactured by SmithKline Beecham (Cork) Limited - Cidra - Puerto Rico<br>* 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)<br>Drug: Paxil CR 25 mg manufactured by GlaxoSmithKline Inc. - Mississauga - Canada<br>* Paroxetine Hydrochloride 25 mg tablet with controlled release (Paxil CR), once a day, manufactured by GlaxoSmithKline Inc. - Mississauga - Canada (test formulation)<br>|
| Active Comparator: Paxil CR Test<br>Paroxetine Hydrochloride 25 mg tablet with controlled release (Paxil CR), once a day, manufactured by GlaxoSmithKline Inc. - Mississauga - Canada, in Period 1, followed by Paroxetine Hydrochloride 25 miligrams(mg) tablet with controlled release (Paxil CR), once a day, manufactured by SmithKline Beecham (Cork) Limited - Cidra - Puerto Rico, in Period 2 | Drug: Paxil CR 25 mg manufactured by SmithKline Beecham (Cork) Limited - Cidra - Puerto Rico<br>* 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)<br>Drug: Paxil CR 25 mg manufactured by GlaxoSmithKline Inc. - Mississauga - Canada<br>* Paroxetine Hydrochloride 25 mg tablet with controlled release (Paxil CR), once a day, manufactured by GlaxoSmithKline Inc. - Mississauga - Canada (test formulation)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Days 14 to 17 (period 1) and Days 23 to 24 (Period 2) | 
| 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. | Days 14 to 17 (period 1) and Days 23 to 24 (Period 2) | 
| 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. | Days 14 to 17 (period 1) and Days 23 to 24 (Period 2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bioequivalence, Paroxetine reference/test, healthy volunteers, Fed condition