Controlled-release Paroxetine in Major Depressive Disorder (Double-blind, Placebo-controlled Study)
Condition: Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: paroxetine IR 10mg tablet; paroxetine IR 20mg tablet; matched placebo to paroxetine IR 10mg or 20mg; Paroxetine CR 12.5mg tablet; Paroxetine CR 25mg tablet; matched placebo to paroxetine CR 12.5mg or 25mg
Intervention description: 1 or 2 tablets once a day; 1 tablet once a day; 1 or 2 tablets once a day; 1 or 2 tablets once a day; 1 or 2 tablets once a day; 1 or 2 tablets once a day
Intervention MeSH terms: Paroxetine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 416.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Immediate-release formulation of paroxetine (paroxetine IR); HAM-D (17 items); Controlled-release formulation of paroxetine (paroxetine CR)

Summary:

      This is a randomized, double-blind, placebo-controlled, parallel group study to evaluate the
      efficacy of controlled-release (CR) formulation of paroxetine orally administered to patients
      with major depressive disorder (MDD) at a dose level in the range of 25 - 50 mg/day (initial
      dose level, 12.5 or 25 mg/day) once daily after evening meal for 8 weeks based on the
      decrease in HAM-D (Hamilton Depression Rating Scale) total score, to evaluate the safety
      based on adverse events, laboratory data and vital signs, and to describe the efficacy and
      safety of immediate release (IR) formulation of paroxetine.
    

Eligibility criteria:

        Inclusion Criteria:

        <at the start of placebo run-in phase> Only the patients who meet all of the following
        conditions at Week -1 (at the start of placebo run-in phase) will be enrolled in this
        study. The hospitalization status will be no object. and Gender: No object.

          -  Target disease: Patients diagnosed as having one of the following depressive disorders
             based on DSM-IV-TR classification in conjunction with M.I.N.I. (The Mini International
             Neuropsychiatric Interview, Japanese version 5.0.0. [2003]) and showing currently a
             symptom of depression or depressed sate

          -  Major depressive disorder, single episode (296.2) (excluding those accompanied by
             comorbid psychiatric disorders)

          -  Major depressive disorder, recurrent (296.3) (excluding those accompanied by comorbid
             psychiatric disorders)

          -  Age: >= 20 years (at the time of obtaining consent)

          -  Consent: Patients from whom written consent to participate in this study can be
             obtained

          -  Gender:

          -  Female patients of childbearing potential can be enrolled. But, such patients who can
             be enrolled are limited to only those who are negative in the pregnancy test performed
             at the start of the placebo run-in phase and who agree to receive a pregnancy test at
             the time point defined in the study period and surely perform any of the contraceptive
             methods.

          -  Male subjects must abstain from (or use a condom during) sexual intercourse with a
             pregnant or lactating female. Male subjects must abstain from or use a condom plus
             spermicidal agent (foam/gel/film/cream/suppository) during sexual intercourse with a
             female of child-bearing potential.

          -  Patients whose HAM-D (17 items) total score is >= 20 points

          -  Patients whose duration of current episode at least 12 weeks but no longer than 24
             months

          -  Patients whose score of "depressed mood" (HAM-D Item 1) is >= 2 points

          -  QTc<450 millisecond (msec) or <480 msec for patients with Bundle Branch Block - values
             based on either single ECG values or triplicate ECG averaged QTc values obtained over
             a brief recording period.

        For the purposes of these criteria, QTc B (Bazett's correction) is defined as (QT interval
        [msec]) /(square root of RR interval [seconds])

        <at the start of treatment phase> Only the patients who meet all of the following
        conditions at Week -1 (at the start of the placebo run-in phase) and Week 0 (at the start
        of treatment phase) can be shifted to the treatment phase.

          -  Patients whose HAM-D (17 items) total score is >=20 points

          -  Patients whose score of "depressed mood" (HAM-D Item 1) is >=2 points

        Exclusion Criteria:

        <at the start of placebo run-in phase> The patients who are meeting any of the following
        conditions at Week -1 (at the start of placebo run-in phase) must not be enrolled in this
        study.

          -  Patients whose primary diagnosis is a disorder classified to Axis I other than major
             depressive disorder in DSM-IV-TR classification (dysthymic disorder, eating disorder,
             specific phobia (monophobia), posttraumatic stress disorder, obsessive-compulsive
             disorder, panic disorder, etc.)

          -  Patients with a current DSM-IV-TR Axis II diagnosis that suggested non-responsiveness
             to pharmacotherapy or non- compliance with the protocol (e.g., antisocial or
             borderline personality disorder)

          -  Patients with a history or complication of another (non-MDD) mental disorder
             (schizophrenia, etc.)

          -  Patients with a history or complication of manic episodes

          -  Patients diagnosed as having an attentional deficit disorder or hyperactivity disorder

          -  Patients diagnosed as having a pervasive development disorder or mental retardation

          -  Patients diagnosed as abusing or dependent on alcohol or drug within one year before
             the Week -1 visit

          -  Patients who have undergone electroconvulsive therapy within one year before the Week
             -1 visit for the treatment of the current episode

          -  Patients who have a history of treatment with depot neuroleptics

          -  Patients with a history of serotonin syndrome or neuroleptic malignant syndrome

          -  Patients with a >= 3-point score of "suicide" (HAM-D Item 3) or patients whose
             Columbia Suicide Severity Rating Scale (C-SSRS) assessment suggests that they are or
             have been at significant risk for harming themselves or have actually harmed
             themselves, or who, in the opinion of the investigator (subinvestigator), are at
             significant risk for harming self or others.

          -  Patients with a history of suicide attempt, self-injurious action (excluding action
             with no intention of suicide) or overdosage (excluding apparently accidental
             overdosage)

          -  Patients who have taken another investigational product or a drug used in a
             post-marketing clinical study within 12 weeks before the Week -1 visit

          -  Patients with glaucoma

          -  Patients with a convulsive disorder such as epilepsy or a history of it

          -  Patients using a drug increasing an onset risk of bleeding, patients with a bleeding
             tendency or bleeding diathesis

          -  Patients complicated with severe renal or hepatic dysfunction

          -  Patients complicated with serious organic brain disorder

          -  Patients with a history or complication of cancer or malignant tumor

          -  Patients complicated by chronic hepatitis B or C being positive in test of hepatitis B
             surface antigen (HbsAg) or hepatitis C antibody

          -  Pregnant, lactating or possibly pregnant female patients, and female patients wishing
             to be pregnant during the study period

          -  Patients who have previously been unresponsive to paroxetine therapy (e.g. >4wks
             unresponsive to paroxetine for depression).

          -  Patients with a history of having discontinued treatment due to an adverse event
             caused by paroxetine

          -  Patients with a history of hypersensitivity to paroxetine.

          -  Patients judged ineligible to participate in this study by the investigator or
             subinvestigator

        Exclusion criteria < at the start of treatment phase> The patients who are meeting any of
        the following conditions at Week 0 (at the start of treatment phase) must not be allowed to
        the treatment phase.

          -  Patients with a 3 or more-point score of "suicide" (HAM-D Item 3) or with a strong
             suicidal tendency by C-SSRS and investigator clinical judgement.

          -  Patients whose HAM-D (17 items) total score at the Week 0 visit has changed ±25 %, or
             exceeding the range of ±25 % of the score at the Week -1 visit

          -  Patients whose Drug 1 (run-in placebo) compliance rate in the period from Week -1 to
             Week 0 has been < 80 %

          -  Patients judged ineligible as the study subjects by the investigator or
             subinvestigator