Repeat Dose Study of Controlled-Release Paroxetine Tablets and Immediate-Release Paroxetine Tablets in Healthy Japanese Male Subjects

Study Overview
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Brief Summary
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The primary purpose of this study is to compare the steady-state pharmacokinetic profile of paroxetine CR (controlled-release) at the dosage of 25mg/day using the proposed final market tablet of CR 25mg in Japan with that of standard paroxetine IR(immediate-release ) at the dosage of 20mg/day using the currently marketed tablet of IR 20mg in Japan.

Detailed Description
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This study is an open, randomized, repeat dose, two-period crossover design in Japanese healthy male volunteers. This clinical trial is designed primarily to compare the steady-state pharmacokinetic profile of paroxetine CR at the dosage of 25mg /day (25mg once daily for 14 days) using the proposed final market tablet of CR 25mg in Japan with that of paroxetine IR at the dosage of 20mg/day (20mg once daily for 14 days) using the currently marketed IR 20mg tablet in Japan, by the crossover oral repeat dosing manner.

Official Title
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A Steady-state, Two-period Crossover Study to Compare the Pharmacokinetic Profile of Paroxetine After Repeated Daily Dosing of the Controlled-release Paroxetine Tablet (25 mg) With That of the Standard Immediate-release Paroxetine Tablet (20 mg) in Healthy Japanese Male Subjects

Conditions
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Depressive Disorder

Intervention / Treatment
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* Drug: Paroxetine CR and Paroxetine IR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Japanese adult males between 20 and 64 years of age inclusive BMI 18.50 or higher and < 25.00 kg/m2, and bodyweight 50 kg or higher Non-smokers AST, ALT, ALP, gamma-GTP and total-bilirubin are below the upper limit of normal range QTc(B) interval <450 msec Able to attend all visits and complete the study Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form Exclusion Criteria: Any clinically relevant abnormality on the screening physical examination, vital signs, 12-lead ECG and/or clinical laboratory tests Medical history that is not considered as eligible for inclusion in this study by the investigator Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of asymptomatic gallstones) History of psychiatric disorder or suicide attempts or behaviours History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs History of sensitivity to any of the paroxetine formulations, or components thereof Positive for urine drug screening Participation in another clinical study or post-marketing study in which the subject is or will be exposed to an investigational or a non-investigational product or device Participation in a clinical study or post-marketing study with an investigational or a non-investigational product or device within 4 months of preceding the first dose of study medication History of drug or other allergy, or idiosyncrasy, excluding a pollen allergy without current symptoms History of drug abuse, or current conditions of drug abuse or alcoholism History of regular alcohol consumption exceeding, on average, 14 drinks/week (1 drink = 150 mL of wine or 350 mL of beer or 45 mL of 80 proof distilled spirits) within 6 months of screening Use of prescription or no-prescription drugs, including vitamins, crude drug, herbal and dietary supplements (including St John's Wort) within 14 days prior to the first dose of study medication Unwillingness or inability to follow the procedures outlined in the protocol Consumption of grapefruit or grapefruit-containing products from 7 days prior to the first dose of study medication Positive for syphilis, HIV antibody and antigen, Hepatitis B surface antigen, Hepatitis C antibody or HTLV-1 antibody Donation of blood in excess of 400mL within the previous 4 months or 200mL within the previous 1 month to the first dose of study medication

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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Male

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 |
| --- | --- |
| Experimental: Open label treatment with 2-period crossover design<br>Group 1: Paroxetine CR 25 mg/day for 14 days / Paroxetine IR 20 mg/day for 14 days. Group 2: Paroxetine IR 20 mg/day for 14 days / Paroxetine CR 25 mg/day for 14 days., PK results will be compared between the Paroxetine CR treatment period and the Paroxetine IR treatment period. | Drug: Paroxetine CR and Paroxetine IR<br>* Randomized, 2-period crossover repeat dosing of Paroxetine CR at 25 mg/day for 14 days and Paroxetine IR at 20 mg/day for 14 days in Japanese healthy male volunteers<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters of plasma paroxetine after 14-days repeat dosing of paroxetine CR at 25mg/day or paroxetine IR at 20mg/day |  | up to 96 hours after dosing on Day 14 of each treatment period of paroxetine CR or paroxetine IR | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability in healthy Japanese male volunteers during and after the repeat dosing period of paroxetine CR or paroxetine IR |  | During the 14-days repeat dosing period and up to 96 hours after the last dose of paroxetine CR or paroxetine IR | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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controlled-release tablet, repeat dose, immediate-release tablet, paroxetine, safety, crossover, pharmacokinetics, steady-state, Japanese healthy male volunteers, tolerance