Clinical trial NCT02232555 (phase 3, status: completed)
Conditions: depressive disorder, major
ICD codes: F33.0, F33.1, F33.9, F32.0, F32.1, F32.9, F33.40
Drugs: duloxetine, placebo
SMILES: CN(C)CCC[C@]1(OCC2=C1C=CC(=C2)C#N)C1=CC=C(F)C=C1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  Male or female outpatients who meet the criteria for MDD according to the Diagnostic
             and Statistic Manual of mental disorders, 4th edition (DSM-IV) criteria and confirmed
             by Mini International Neuropsychiatric Interview (MINI)

          -  Montgomery-Asberg Depression Rating Scale (MADRS) score ≥20 at screening and baseline
             (Visits 1 and 2)

          -  Patients must have had at least one previous episode of depression in their medical
             history

          -  Painful physical symptoms (PPS) with a score ≥ 3 on the BPI-SF scale for average pain
             at screening and baseline

          -  Patient aged 18 years or older at the screening visit

          -  CGI-Severity score ≥ 4 at Visits 1 and 2

          -  Patients willing and able to comply with the scheduled visits, tests and procedures
             required by the protocol

          -  Written informed consent obtained at the screening visit, in accordance with Good
             clinical practice (GCP) and local regulatory requirements, prior to any study
             procedure

        Exclusion Criteria:

        Neuro-psychiatric exclusions

          -  Lack of response of the current episode to 2 or more adequate courses of
             antidepressant therapy given at a clinically appropriate dose and for a sufficient
             length of time in the judgement of the investigator

          -  Any anxiety disorder as a primary diagnosis within the past 6 months (including panic
             disorder, obsessive-compulsive disorder, posttraumatic stress disorder, generalized
             anxiety disorder, and social phobia). Note: Specific phobias (i.e. agoraphobia,
             arachnophobia, etc.) will be allowed

          -  Any diagnosis of bipolar disorder, schizophrenia, or other psychotic disorders

          -  Presence of an Axis II disorder which, in the judgement of the investigator, would
             interfere with compliance with the study protocol

          -  History of serious suicide attempt or patient judged to be at serious suicidal risk in
             the opinion of the investigator and / or score > 2 for question 10 (suicide) of the
             MADRS

          -  History of drug dependence, including alcohol or benzodiazepines, according to DSM-IV,
             in the previous year

          -  Positive urine screen for drug abuse (cannabis, benzodiazepines, barbiturates,
             opiates, cocaine, amphetamines)

        Other medical exclusions

          -  Patients requiring continuous treatment with analgesics (> step 2 WHO definition)
             because of chronic pain (> 6 months)

          -  Patients with organic pain syndromes

          -  Epilepsy or history of seizure disorder or of a treatment with anticonvulsant
             medication for epilepsy or seizures

          -  Patients with a known diagnosis of raised intraocular pressure or at risk of acute
             narrow-angle glaucoma

          -  Known diagnosis of congenital galactosaemia, glucose or galactose malabsorption
             syndrome, or lactose deficiency

          -  Patients with severely impaired renal function, defined by a creatinine clearance < 30
             mL/min (creatinine clearance was calculated by the central laboratory from the
             screening safety laboratory test

          -  Acute liver injury (such as hepatitis) or severe (Child-Pugh Class C) cirrhosis

          -  Abnormal initial ECG findings according to investigator's judgement

          -  Serious medical illness or clinically significant laboratory abnormalities which, in
             the judgement of the investigator, are likely to require medication/ intervention or
             hospitalization during the course of the study

          -  Women of childbearing potential not using a medically accepted means of contraception
             when engaging in sexual intercourse (e.g. intrauterine device, oral contraceptive,
             contraceptive patch, implant, or barrier devices)

          -  Women who are pregnant or breast-feeding

        Pharmacological and other exclusions

          -  Participation in another clinical trial within 30 days prior to screening (Visit 1)

          -  Patients who have previously completed or withdrawn from this or any other study
             investigating duloxetine or have previously been treated with duloxetine

          -  Treatment with a monoamine oxidase inhibitor (MAOI) within 14 days prior to Visit 2 or
             potential need to use a MAOI within 5 days after discontinuation of study drug

          -  Treatment with fluoxetine within 28 days prior to Visit 2

          -  Treatment with any of excluded medications (listed in Protocol) within 7 days prior to
             Visit 2

               -  (excepted MAOI within 14 days and fluoxetine within 28 days)

          -  Frequent and/or severe allergic reactions with multiple medications. Known
             hypersensitivity to duloxetine or any of the inactive ingredients

          -  Electro-convulsive Therapy (ECT) or Transcranial Magnetic Stimulation (TMS) within one
             year prior to screening

          -  Initiation or discontinuation of depression-oriented psychotherapeutic treatment (e.g.
             behavioural therapy, psychoanalytic therapy, cognitive therapy etc.) within 6 weeks
             prior to screening visit or planned use of such treatment at any time during the study