Clinical Evaluation of BRL29060A (Paroxetine Hydrochloride Hydrate) in Posttraumatic Stress Disorder (PTSD)
Condition: Post-Traumatic Stress Disorder; Stress Disorders, Post-Traumatic
MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Intervention: paroxetine; placebo
Intervention description: BRL29060A (paroxetine hydrochloride hydrate, hereafter paroxetine) administered orally over the dose range of 20 mg to 50 mg once daily after supper for 12 weeks in Japanese patients with posttraumatic stress disorder (PTSD); placebo
Intervention MeSH terms: Paroxetine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 5.0
Sex: All
Minimum age: 20 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: PTSD (Posttraumatic Stress Disorder); CAPS; fMRI; Paroxetine

Summary:

      This is a single-blind, placebo-controlled, parallel group study to evaluate the efficacy of
      BRL29060A (paroxetine hydrochloride hydrate, hereafter paroxetine) administered orally over
      the dose range of 20 mg to 50 mg once daily after supper for 12 weeks in Japanese patients
      with posttraumatic stress disorder (PTSD) as assessed by the change from baseline in CAPS-SX
      total score. Also the effect of paroxetine on regional cerebral blood flow (rCBF) induced by
      subthreshold emotional arousing (or symptom stimulating) tasks will be determined using
      functional magnetic resonance imaging (fMRI) for exploratory assessment of the correlation
      between the change in rCBF and the efficacy.

      The sample size is 30 subjects. The study period consists of 4 weeks of run-in phase, 12
      weeks of treatment phase, 0-3 weeks of taper phase and follow-up examination at 2 weeks after
      the last dose, for a total of 18-21 weeks.

      Subjects will visit the clinic at the start of run-in phase, Week -2, the start of treatment
      phase, Weeks 2, 4, 6, 8 and 12 of treatment, and follow-up examination.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients who are primarily diagnosed with PTSD (Posttraumatic Stress Disorder: 309.81)
             using DSM-IV-TR criteria. The CAPS-DX (Clinician-Administered PTSD Scale-DX) and
             M.I.N.I. (The Mini International Neuropsychiatric Interview, Japanese version 5.0.0.
             [2003]) will be used for diagnosis

          -  Pathologic condition: Patients who experienced a motor vehicle accident (MVA) with
             severe or potential severe physical injury more than 3 months ago but less than 12
             months ago

          -  Patients aged 20 and <65 at the time of signing the Informed consent

          -  Male and female patients

          -  Inpatient/outpatient status: Both are permitted

          -  Patients who are able to give written informed consent in person (i.e., patients who
             are capable of giving written informed consent on their own)

          -  Patients whose combined score of the CAPS-SX standard B, C, and D is over 50

        Exclusion Criteria:

          -  Patients primarily diagnosed with a DSM-IV-TR Axis I disorder other than PTSD (e.g.
             major depressive disorder, dysthymic disorder, specific phobia [simple phobia],
             obsessive-compulsive disorder, panic disorder, etc.) within 6 months of week -4 (start
             of baseline phase)

          -  Patients presenting with a current major depressive episode that preceded the
             diagnosis of PTSD

          -  Patients receiving disability payments due to PTSD or other psychiatric diseases

          -  Patients currently engaged in compensation litigation whereby personal gain would be
             achieved from prolonged symptoms of PTSD or any other psychiatric disorders

          -  Patients who meet the DSM-IV-TR criteria for substance abuse or dependence (alcohol or
             drugs) within 6 months of Week -4 (start of baseline phase)

          -  Patients with history of a suicide attempt within 6 months before Week -4 (start of
             baseline phase), or have, in the opinion of the investigator, "C. high risk of
             suicide" according to the MINI at Week -4

          -  Patients who are pregnant, lactating or of childbearing potential and are likely to
             become pregnant

          -  Patients receiving electro-convulsive therapy (ECT) prior to Week -4 (start of
             baseline phase)

          -  Patients receiving another investigational product within 12 weeks before Week -4
             (start of baseline phase)

          -  Patients with a history or complication of manic psychosis

          -  Patients with a history or complication of convulsive disorder (epilepsy, etc.)

          -  Patients with a diagnosis or complication of a cognitive disorder (MMSE <=24 points)

          -  Patients with a history and complication of serious cerebral organic disorder. (e.g.
             cerebrovascular disorder, meningitis, degenerative disease and other neurological
             disorders and seizures; however, bleeding in the upper arachnoid membrane should not
             be excluded)

          -  Patients unable or unwilling to undergo the fMRI procedure (e.g., cerebrovascular
             clipping surgery, pacemaker, any internal metals with magnetism, and claustrophobia)

          -  Patients with glaucoma

          -  Patients with a known tendency for bleeding or those with predisposing conditions

          -  Patients with a history of hypersensitivity to paroxetine

          -  Patients with serious physical symptoms (cardiac, hepatic and renal dysfunction, or
             hematopoietic dysfunction, etc.). For seriousness, Grade 3 of "Criteria for
             seriousness of adverse reactions to drugs, etc. (Yakuan No.80)" is used as an index

          -  Patients with a history or complication of cancer or malignant tumour

          -  Patients with chronic hepatitis type B and/or C which is positive of hepatitis B
             surface antigen (HBsAg) and/or hepatitis C antibody

          -  Others whom the investigator or sub-investigator considers ineligible for or unable to
             participate in the investigation

          -  Criteria at Week 0 (start of Treatment Phase):

        Subjects whose drug compliance rate for Drug 1 (Run-in Phase placebo) is <80% between Week
        -4 and Week 0;

        Subjects whose CAPS-SX total score of the standard B, C, and D at Week 0 varied by 25% or
        more compared with those at Week -2