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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- GlaxoSmithKline
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Pharmacokinetic parameters of plasma paroxetine after 14-days repeat dosing of paroxetine CR at 25mg/day or paroxetine IR at 20mg/day
Study Overview
Brief Summary
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
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to 64 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
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.
Intervention: Paroxetine CR and Paroxetine IR (Drug)
Outcomes
Primary Outcomes
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
Secondary Outcomes
- 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)