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

Official Title: “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”

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.

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.

Intervention(s) in this Clinical Trial

• Drug: Paroxetine CR and Paroxetine IR
  • 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

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Open label treatment with 2-period crossover design
  • 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.

Primary Measures

• Pharmacokinetic parameters of plasma paroxetine after 14-days repeat dosing of paroxetine CR at 25mg/day or paroxetine IR at 20mg/day
  • Time Frame: up to 96 hours after dosing on Day 14 of each treatment period of paroxetine CR or paroxetine IR
    Safety Issue?: No

Secondary Measures

• Safety and tolerability in healthy Japanese male volunteers during and after the repeat dosing period of paroxetine CR or paroxetine IR
  • Time Frame: During the 14-days repeat dosing period and up to 96 hours after the last dose of paroxetine CR or paroxetine IR
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 20 Years

Maximum Age for this Clinical Trial: 64 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: GlaxoSmithKline Industry

Overall Clinical Trial Officials and Contacts

GSK Clinical Trials Study Director GlaxoSmithKline  

Information obtained from ClinicalTrials.gov on February 02, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01000857

Study ID Number: 112812

ClinicalTrials.gov Identifier: NCT01000857

Health Authority: Japan: Pharmaceutical and Medical Device Agency