Pipamperone/Citalopram (PNB01) Versus Citalopram (CIT) and Versus Pipamperone (PIP) in Major Depressive Disorder (MDD)
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: PNB01 fixed dose combination of pipamperone and citalopram; Citalopram; Pipamperone
Intervention description: oral once daily administration; oral once daily administration; oral once daily administration
Intervention MeSH terms: Dexetimide; Pipamperone; Citalopram; Escitalopram
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 555.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The overall objective of this trial is to demonstrate clinically relevant superior
      antidepressant efficacy of the fixed dose combination PNB01 (low dose pipamperone and
      citalopram) over reference antidepressant treatment with citalopram alone, and a low dose of
      psychoactive pipamperone alone in patients with moderate to severe Major Depressive Disorder.

      This study was specifically designed to assess patient related outcome (PRO) parameters using
      an Interactive Voice Response System (IVRS) via telephone.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patient is informed and given ample time and opportunity to think about her/his
             participation and has given her/his written informed consent.

          2. Patient understands the investigational nature of the trial and is willing and able to
             comply with the trial requirements.

          3. Patient is male or female, aged ≥ 18 years.

          4. Patient has MDD according to the DSM IV-R criteria with an existence of depressed mood
             (DSM-IV-R Crit. A1) and loss of interest/anhedonia (DSM-IV-R Crit. A2) as confirmed by
             the MINI, lasting for at least 4 weeks and no longer than 18 months (78 weeks) for the
             current episode, and causing significant functional impairment (DSM-IV-R MDD C-
             criterion).

          5. CGI-S rating of at least 4 and a minimum MADRS total score of 26 using IVRS ePRO at
             Baseline.

        Exclusion Criteria:

          1. Patient is pregnant, nursing, or is a woman of child-bearing potential who is not
             surgically sterile, 2 years postmenopausal, or who does not consistently use 2
             combined effective methods of contraception (including at least 1 barrier method),
             unless sexually abstinent.

          2. Existence of Mood Disorder with psychotic features and/or high suicidality risk, as
             confirmed by MINI.

          3. Concomitant diagnosis of any additional primary Axis I disorder and presence of any of
             the following co-morbid disorders: (Hypo)manic episode, Panic Disorder (limited
             symptom attacks allowed), Obsessive Compulsive Disorder, Post-traumatic Stress
             Disorder, Alcohol dependence, any other Substance abuse and/or dependence, Psychotic
             Disorder, Eating Disorder, or General Anxiety Disorder, as confirmed by MINI.

          4. Concomitant diagnosis of any primary Axis II disorder.

          5. Patient is hospitalized.

          6. Patient has a clinically relevant renal dysfunction (e.g. GFR <60mL/min).

          7. Patient has hepatic dysfunction (total bilirubin >2.0mg/dL or alanine aminotransferase
             (ALT) and/or aspartate aminotransferase (AST) greater than 2 times the upper limit of
             the reference range).

          8. Patient has a malignant neoplastic disease, a documented history of epilepsy (juvenile
             convulsions excepted) or a documented, in the opinion of the investigator, clinically
             relevant risk of bleeding (eg. severe bleeding disorder, treatment with warfarin, …).

          9. Patient with a documented history or concomitant diagnosis or significant risk of
             cardiac arrhythmia or dysrhythmia, including a QTc interval of ≥500 ms at Baseline.

         10. Patient has any other medical or psychiatric condition, which in the opinion of the
             investigator, can jeopardize or would compromise the patient's ability to participate
             in this trial or that would interfere with trial assessments.

         11. Patient with documented alcohol or drug abuse, or having a positive standard screen
             for alcohol or drugs (including benzodiazepines and opioids).

         12. Patient received, in the past 7 days treatment with any psychoactive drug prior to
             randomization, including typical and atypical antipsychotics, hypnotics,
             antidepressants, anxiolytic drugs, anticonvulsive therapy, opioids, monoamine oxidase
             (MAO) inhibitors, sedative antihistamines, psychostimulants or amphetamines, dopamine
             D2 receptor antagonists, butyrophenones, metoclopramide, lithium, anticonvulsants,
             benzodiazepines, or barbiturates. If patient has received such therapy, a washout
             period of at least 7 days prior to baseline is required before inclusion in this trial
             (except fluoxetine: 4 weeks, and St John's Wort or MAO inhibitors: within 2 weeks).

         13. Concomitant treatment with diuretics, QT prolongation drugs, or dopamine agonists.

         14. Resistant depression defined as having failed to respond to either: a/ 2 previous
             antidepressants at an adequate dose administered for at least 4 weeks during the
             current episode; b/ augmentation therapy with any atypical antipsychotic drug

         15. Electroconvulsive therapy (ECT) or repetitive Transcranial Magnetic Stimulation
             therapy (rTMS) within the last 6 months; Vagus Nerve Stimulation (VNS) or Deep Brain
             Stimulation (DBS) ever.

         16. Formal psychotherapy or alternative treatment for 1 week prior to or during the study.

         17. Patient has participated in another trial of an investigational agent (including
             medical device) within the last 3 months prior to baseline or is currently
             participating in another trial of an investigational drug.

         18. Known hypersensitivity to any of the study drugs