Bioequivalence Study of Paroxetine Immediate Release (IR) Tablets Manufactured in GlaxoSmithKline Tianjin (GSKT) and Mississauga Sites in Healthy Chinese Subjects
Condition: Anxiety Disorders
MeSH terms: Anxiety Disorders
Intervention: Paroxetine IR tablets A; Paroxetine IR tablets B
Intervention description: Paroxetine IR tablets A will be the investigational drug. These are film coated tablets with unit dose strength of 20 milligrams (mg) and will be administered via oral route. These tablets will be manufactured in GSKT.; Paroxetine IR tablets B will be the reference drug. These are film coated tablets with unit dose strength of 20 mg and will be administered via oral route. These tablets will be manufactured in Mississauga.
Intervention MeSH terms: Paroxetine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: In this study, each subject will receive paroxetine IR 40mg A or B in a cross-over manner
Masking: None (Open Label)
Masking description: This study is an open-label treatment period; hence, masking will not be performed.
Enrollment: 85.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Cross-over; Chinese; GSKT; Mississauga; Healthy; Bioequivalence; Paroxetine

Summary:

      Paroxetine is a selective serotonin reuptake inhibitor (SSRI) and paroxetine IR tablets have
      been approved for the treatment of three anxiety indications in China. This bioequivalence
      study will evaluate Paroxetine IR tablets manufactured in GSKT (A) and Mississauga (B) sites
      in healthy Chinese subjects under fasting and fed conditions to support the quality
      consistency evaluation. This is a single dose, open-label, randomized, two-period crossover
      study and will include a screening period (up to 7 days), two open-label treatment periods
      (up to 16 days) and a follow-up phase (up to 14 days after last-dose). The whole study will
      be divided into two groups, one for fasting condition enrolling approximately 36 subjects and
      another for fed condition for which approximately 44 subjects will be enrolled. In both
      groups, eligible subjects will be randomized to receive single dose of Paroxetine IR tablets
      A or B in a cross-over manner.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Able to actively communicate with the investigator and to complete the study-related
             documents; able to understand the contents of the Informed consent form (ICF) and to
             sign a written ICF prior to any study-specific procedures.

          -  Males and females aged between 18 and 45 years inclusive, at the time of signing the
             informed consent.

          -  Non-smoking healthy males and females as assessed by medical history and physical
             examination. Healthy as determined by a responsible and experienced physician, based
             on a medical evaluation including medical history, physical examination, laboratory
             tests and cardiac monitoring. A subject with a clinical abnormality or laboratory
             parameters which are not specifically listed in the inclusion or exclusion criteria,
             outside the reference range for the population being studied may be included only if
             the Investigator (in consultation with the GSK Medical Monitor if necessary) agree and
             document that the finding is unlikely to introduce additional risk factors and will
             not interfere with the study procedures.

          -  Body weight>=50 kilograms (kg) (male) or 45kg(female) and Body mass index (BMI) 19.0
             to 26.0 kg per meter square (kg/m^2) (inclusive).

          -  A female subject is eligible to participate if she is of: Child-bearing potential with
             negative pregnancy test as determined by serum or urine human chorionic gonadotropin
             (hCG) test at screening or prior to dosing and agrees to use the one of the defined
             contraception method during the study and until follow up contact.

          -  Male Subjects with female partners of child-bearing potential must agree to use one of
             the defined contraception methods during the study and until follow up contact.

          -  ALT, ALP and total bilirubin <=1.5x upper limit of normal (ULN) (isolated bilirubin
             >1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35
             percent).

          -  Based on single or averaged corrected QT interval (QTc) values of triplicate ECGs
             obtained over a brief recording period: QTc < 450 milliseconds (msec); or QTc < 480
             msec in subjects with bundlebranch block.

        Exclusion Criteria:

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).

          -  Drug or alcohol abuse or dependency within one year prior to enrolment. History of
             regular alcohol consumption within one year of the study defined as: an average weekly
             intake of >14 drinks. One drink is equivalent to 12 grams (g) of alcohol: 12 ounces
             [360 milliliter (mL)] of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80
             proof distilled spirits.

          -  Unstable disease conditions; any laboratory measurements assessed by the investigator
             as clinically relevant (including ECG, hematology, biochemistry and urine analysis,
             etc.)；any disorder that might interfere with the absorption, distribution, metabolism
             or excretion of the study drug; or in the investigator's opinion the disease may lead
             to safety concerns or interfere with the pharmacokinetics assessment.

          -  Subjects with concurrent or previous neuropsychological disorders, as assessed by
             Columbia Suicide Severity Rating Scale or by the investigator, have suicidal tendency,
             or have committed suicidal behavior/attempt.

          -  Known history of cerebral trauma, previous cerebral disorders, seizures or eating
             disorder, and other conditions that in the investigator's opinion may increase the
             risk of seizures.

          -  Exposure to more than four new chemical entities within 12 months prior to the first
             dosing day.

          -  Unable to refrain from the use of prescription or non-prescription drugs, including
             vitamins, herbal and dietary supplements (including St John's Wort) within 14 days or
             5 half-lives (whichever is longer) prior to the first dose of study medication.

          -  In subjects with concomitant use of monoamine oxidase inhibitors (MAOIs) (including
             linezolid, an antibiotic which is a reversible non-selective MAOIs and
             methylthioninium chloride (methylene blue)) or within two weeks of terminating
             treatment with MAOIs.

          -  In subjects with concomitant use of thioridazine or pimozide.

          -  The subject has participated in a clinical trial and has received an investigational
             product within 90 days prior to the first dosing day in the current study, or has
             participated in a clinical trial without receiving any investigational product within
             30 days prior to the first dosing day in the current study.

          -  A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
             result within 3 months.

          -  Serum human immuno-deficiency virus (HIV) antibody or Syphilis antibody positive.

          -  A positive pre-study drug/alcohol screen.

          -  Known allergy to paroxetine IR Tablets or any of its components.

          -  Blood donation in excess of 400 mL in the 3 months prior to enrolment.

          -  Obvious evidence of active hematological diseases, or significant blood loss in the
             last 3 months. History of sensitivity to heparin or heparin-induced thrombocytopenia.

          -  Lactating females or women of child bearing potential used oral or implanted
             contraceptives within the 30 days prior to enrolment, or received injections of
             chronically acting contraceptives in the 1 year prior to study initiation.

          -  Other conditions which, in the Investigator's judgment, render subjects unsuitable for
             the clinical study.