A Randomized, Double-blind, Two-arm Study Comparing the Efficacy and Safety of Trazodone Contramid® OAD and Placebo in the Treatment of Unipolar Major Depressive Disorder.
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: Trazodone Hydrochloride (HCl) Extended-Release Tablets; Placebo
Intervention MeSH terms: Trazodone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 412.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Unipolar

Summary:

      The purpose of this study was to demonstrate efficacy, safety and clinical benefit of
      Trazodone Contramid® OAD (Once A Day) in the treatment of Unipolar Major Depressive Disorder
      (MDD).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males or females.

          -  Aged 18 years or older.

          -  Fulfills Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)
             criteria for Unipolar Major Depressive Disorder (MDD) (Axis I) as confirmed by the
             Mini-International Neuropsychiatric Interview (MINI).

          -  The primary DSM-IV Axis I diagnosis should be MDD (296.22, 296.23, 296.32, 296.33);
             any subject meeting criteria for another, non excluded Axis I disorder, must
             demonstrate MDD as the primary disorder.

          -  The current episode of MDD should have lasted for a minimum of 1 month, whether the
             patient has been diagnosed with one single or recurrent episodes.

          -  Presence of dysphoria for most days over the past four weeks.

          -  Montgomery-Åsberg Depression Rating Scale (MADRS) total score of at least 26 at
             screening and baseline.

          -  Oral and written language comprehension at a level sufficient to comply with the
             protocol and to complete study-related materials.

          -  Sign and date a written Informed Consent Form (ICF) approved by a Research Ethic Board
             (REB) which has also been signed and dated by the Investigator prior to study
             participation.

        Exclusion Criteria:

          -  DSM-IV Major Depressive Disorder Specifiers: [a] With Catatonic Features; [b] With
             Postpartum Onset; [c] With Seasonal Pattern;

          -  Presence of any of the following DSM-IV Axis I disorders: generalized anxiety
             disorder, panic disorder, social phobia, obsessive-compulsive disorder, post-traumatic
             stress disorder, eating disorder, bipolar disorder, alcohol/substance abuse or
             dependence (caffeine and nicotine allowed), any psychotic disorder.

          -  Depression secondary to stroke, cancer or other severe medical illnesses.

          -  Positive urine drug screen at screening visit.

          -  History or present condition of any DSM-IV Axis II disorder.

          -  History of treatment refractory major depressive episodes defined as incomplete or no
             therapeutic response to two prior courses of at least one month of conventional
             antidepressant drug treatment in adequate dosages.

          -  Currently in psychotherapy (at least one session in the past month with a plan for
             continuing) with a licensed/registered/certified mental health provider, marriage
             counselor, or family therapist.

          -  Meet criteria for high suicide risk on the MINI suicide scale, or in the opinion of
             the investigator is inappropriate for the trial due to clinically significant suicidal
             or homicidal potential.

          -  Require hospitalization for treatment of the current episode of depression.

          -  Uncorrected hypo- or hyperthyroidism.

          -  A history of seizures other than pediatric febrile seizure.

          -  A history of cardiac arrythmias requiring therapy.

          -  A history of myocardial infarction within 1 year before screening.

          -  Clinically significant abnormal findings of Electrocardiography (ECG), laboratory
             parameters.

          -  Unwilling to discontinue use of any antidepressants, including herbal remedies, for a
             minimum of 5 drug half-lives prior to screening.

          -  Unwilling to discontinue use of prohibited medications for a minimum of 5 drug
             half-lives prior to screening.

          -  Treatment within the last 3 weeks with Monoamine Oxidase (MAO) inhibitors.

          -  Use of the following concomitant treatment during the study:

               -  medications causing QT prolongation (e.g. amiodarone, droperidol, erythromycin).

               -  medications causing PR prolongation (e.g. digoxin).

               -  Anti -psychotics (e.g. haloperidol).

               -  protease inhibitors such as ritonavir and indinavir.

          -  Hormonal treatment (e.g. estrogen, oral contraceptives) which has started within 3
             months of study entry.

          -  Treatment with another investigational agent within the last 30 days.

          -  Known and documented allergy to trazodone or any structurally similar drugs.

          -  Previous failure of treatment with trazodone, or previous discontinuation of treatment
             with trazodone due to Adverse Events.

          -  Bowel disease causing malabsorption.

          -  Serious, unstable illnesses during the 3 months before screening including but not
             limited to: hepatic, renal, gastroenterologic, respiratory, cardiovascular (including
             ischemic heart disease), endocrinologic, neurologic, immunologic or hematological
             disease.

          -  Pregnant or lactating, or is of childbearing potential and not willing to use an
             approved method of contraception.

          -  Significant liver disease, defined as active hepatitis or elevated liver enzymes >3
             times the upper boundary of the normal range.

          -  Significant renal disease, defined as Blood Urea Nitrogen (BUN) and/or creatinine >3
             times the upper boundary of the normal range clearance.

          -  Any other condition that, in the opinion of the investigators, would adversely affect
             the patient's ability to complete the study or its measures.