A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Fixed Dose Study Evaluating the Efficacy and Safety of Orvepitant in Subjects With Major Depressive Disorder
Condition: Depressive Disorder, Major
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: orvepitant; placebo
Intervention description: Neurokinin-1 (NK-1) antagonist; inactive placebo to match orvepitant 30 and 60 mg dosage forms
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 328.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: depression; QIDS-SR; HAMD-17; orvepitant; MDD; neurokinin-1 antagonist; double-blind; Phase II; randomized; efficacy; placebo; safety

Summary:

      This is a 6-week, randomised, multicenter, double-blind, placebo controlled, fixed dose
      parallel group study to assess the efficacy and safety of orvepitant (30 and 60 mg/day)
      versus placebo in subjects with a diagnosis of a Major Depressive Disorder, whose symptoms
      are considered moderate or severe.

      Following an initial screening visit, subjects fulfilling the study inclusion and exclusion
      criteria will enter a pre-treatment screening phase to permit evaluation of the laboratory
      and ECG assessments and to confirm eligibility for inclusion into the study. This screening
      phase will be a minimum of 7 days, but no longer than 21 days. At the completion of the
      screening period, eligible subjects will be randomised at the baseline visit to receive
      either orvepitant 30mg/day, orvepitant 60mg/day or placebo (equal chance of receiving any of
      the three possible treatments, i.e., a 1:1:1 ratio) for a six-week double-blind treatment
      phase. Those subjects randomised to receive placebo will receive study medication identical
      in appearance to that received by subjects assigned to receive orvepitant 30 or 60mg/day.

      Efficacy will be assessed via standard depression symptom and severity rating scales or
      questionaires. The Hamilton Depression Rating Scale (HAM-D) will be used as the primary
      measure. Secondary efficacy endpoints include the Quick Inventory of Depressive
      Symptomatology (QIDS-SR) and the Clinical Global Impression- Global Improvement and Severity
      of Illness Scale (CGI-I and CGI-S, respectively).

      Safety will be assessed by monitoring for adverse events (side effects) and through periodic
      laboratory evaluations (blood tests), vital signs assessments (e.g., blood pressure, heart
      rate, temperature) and heart function measurements (electrocardiograms, or ECGs).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must have the ability to comprehend the Informed Consent Form.

          -  Male or female outpatients, aged 18-64, inclusive.

          -  A primary diagnosis of major depressive disorder, single episode or recurrent

          -  Subjects must, in the investigator's opinion and based on the subject's history, have
             met depression criteria for at least 8 weeks prior to the Screening Visit.

          -  Subjects with symptom severity considered to be at least moderate to severe by the
             investigator.

          -  Women of childbearing potential are only eligible IF they commit to consistent and
             correct use of an acceptable method of birth control that must be documentation at
             each visit

        Exclusion Criteria:

          -  Subjects whose mood-related symptoms are better accounted for by a diagnosis other
             than depression; subjects diagnosed with Alzheimer's Disease or other form of
             dementia; subjects diagnosed with a current/recent eating disorder such as anorexia
             nervosa or bulimia; subjects with a diagnosed history of schizophrenia,
             schizoaffective disorder, or Bipolar Disorder.

          -  Subjects with any history of a significant abnormality of the neurological system
             (including dementia and other cognitive disorders or significant head injury) or any
             history of seizures (convulsions).

          -  Subjects have a positive urine test at screening for illegal drug use and/or who have
             a history of substance abuse or dependence (alcohol or drugs) within the past 12
             months.

          -  Subjects who are currently receiving regularly scheduled psychotherapy (individual or
             group), plan to start psychotherapy during the trial or have received regularly
             scheduled psychotherapy during the 12 week period prior to the Screening Visit.

          -  Subjects who have a history of failing to respond to adequate treatment with an
             antidepressant, i..e, failure to improve following administration of at least two
             other antidepressants, each given for at least 4 weeks.

          -  Subjects who, in the investigator's judgement, pose a homicidal or serious suicidal
             risk, have made a suicide attempt within the 6 months preceding screening or who have
             ever been homicidal.

          -  Subjects who have received the following treatments for depression in the past:
             electroconvulsive therapy (ECT), vagal stimulation, or transcranial magnetic
             stimulation (TMS) within the 6 months prior to the Screening Visit.

          -  Subjects with an unstable medical disorder; or with a disorder that otherwise would
             likely interfere with the activity of the study medication (orvepitant).

          -  Subjects have any screening laboratory abnormality that in the investigator's
             judgement is considered to be clinically significant.

          -  Subjects with an abnormal thyroid test at the Screening Visit. Subjects maintained on
             thyroid medication must have normal thyroid levels for a period of at least six months
             prior to the Screening Visit.

          -  Subjects have any screening electrocardiography (ECG) finding that in the
             investigator's judgement is considered to be clinically significant.

          -  Women who have a positive pregnancy test at the Screening Visit, a positive urine
             dipstick test at the Baseline (Randomization) Visit, or who are lactating or planning
             to become pregnant within the 4 months following the Screen Visit.

          -  Subjects who have taken other psychoactive drugs within two weeks prior to the
             Baseline Visit i.e. at any time during the Screening period. This includes
             "over-the-counter" psychoactive medications such as St. John's Wort and SAM-e.

          -  Subjects who have taken other drugs within 2 weeks prior to the Baseline visit which
             the investigator feels may interact with the study medication.

          -  Subjects who are currently participating in another clinical trial in which the
             subject is or will be exposed to an investigational or non-investigational drug or
             device, or has done so within the preceding month for studies unrelated to depression,
             or 6 months for studies related to depression.

          -  Subjects who have no contact with an adult on a daily basis. This would exclude
             subjects who are not living with at least one other adult or subjects who do not have
             an adult who contacts them on a daily basis.