Clinical trial NCT01000857: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Depressive Disorder
Keywords: controlled-release tablet
repeat dose
immediate-release tablet
paroxetine
safety
crossover
pharmacokinetics
steady-state
Japanese healthy male volunteers
tolerance
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-10-23
Enrollment: 26
Sex: MALE
Minimum age (years): 20
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetic parameters of plasma paroxetine after 14-days repeat dosing of paroxetine CR at 25mg/day or paroxetine IR at 20mg/day
timeFrame: up to 96 hours after dosing on Day 14 of each treatment period of paroxetine CR or paroxetine IR
Secondary outcomes:
measure: Safety and tolerability in healthy Japanese male volunteers during and after the repeat dosing period of paroxetine CR or paroxetine IR
timeFrame: During the 14-days repeat dosing period and up to 96 hours after the last dose of paroxetine CR or paroxetine IR
Other outcomes:
Locations:
city: Tokyo
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: