Effects of Vortioxetine (Lu AA21004) on the Concentrations of Selected Neurotransmitters in Healthy Male Adults
Condition: Healthy
Intervention: Vortioxetine; Placebo
Intervention description: Encapsulated tablet; Vortioxetine placebo-matching capsules.
Intervention MeSH terms: Vortioxetine
Phase: Phase 1
Study type: Interventional
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 17.0
Sex: Male
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Drug Therapy; pharmacodynamic

Summary:

      The purpose of this study is to evaluate the pharmacodynamics (the drug's effect on the
      body), the pharmacokinetics (the body's handling of the drug), and the safety and
      tolerability of vortioxetine, once daily (QD) in healthy men.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Weighs at least 50 kg and has a body mass index between 19.0 and 32.0 kg/m^2,
             inclusive at Screening.

          -  Males who are nonsterilized and sexually active with a female partner of childbearing
             potential must agrees to use adequate contraception from signing of informed consent
             throughout the duration of the study and for 6 weeks after last dose of study
             medication. The acceptable method of contraception is defined as one that has no
             higher than a 1% failure rate.

        Exclusion Criteria:

          -  Received any investigational compound within 45 days prior to Check-in (Day -2).

          -  Received Lu AA21004 in previous clinical study or as therapeutic agent.

          -  History of or uncontrolled, clinically significant neurologic, cardiovascular,
             pulmonary, central nervous system, hepatic hematopoietic disease, renal metabolic,
             gastrointestinal, or endocrine disease, serious allergy, asthma, hypoxemia,
             hypertension, seizures, allergic skin rash or other abnormality, which may impact the
             ability of the participant to participate or potentially confound study results.

          -  Participant has 1 or more of the following:

               -  Any current psychiatric disorder as defined in the Diagnostic and Statistical
                  Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR).

               -  Current or history of: manic or hypomanic episode, schizophrenia or any other
                  psychotic disorder, including major depression with psychotic features, mental
                  retardation, organic mental disorders, or mental disorders due to a general
                  medical condition as defined in the DSM-IV-TR.

               -  Presence or history of a clinically significant neurological disorder (including
                  epilepsy).

               -  Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple
                  sclerosis, Huntington disease, etc).

               -  Any Axis II disorder.

          -  Has a known hypersensitivity to any component of the formulation of Lu AA21004.

          -  Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -2).

          -  Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol
             abuse (defined as regular consumption of 4 or more units per day) within 1 year prior
             to the Screening visit or is unwilling to agree to abstain from alcohol and drugs
             throughout the study. One unit is equivalent to a half-pint of beer or 1 measure of
             spirits or 1 glass of wine.

          -  The participant intends to impregnate or donate sperm during the course of this study
             or for 6 weeks after last dose.

          -  Has current or recent (within 6 months) gastrointestinal disease that would be
             expected to influence the absorption of drugs (e.g., a history of malabsorption,
             esophageal reflux, peptic ulcer disease, erosive esophagitis; frequent (more than once
             per week) occurrence of heartburn, or any intra-abdominal surgery (except laparoscopic
             cholecystectomy or uncomplicated appendectomy).

          -  Has a history of cancer, other than basal cell or Stage 1 squamous cell carcinoma of
             the skin that has not been in remission for at least 5 years prior to Day 1.

          -  Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C
             antibody at Screening or a known history of human immunodeficiency virus infection.

          -  Has used nicotine-containing products (including but not limited to cigarettes, pipes,
             cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to
             Check-in (Day -2) or is unwilling to abstain from these products for the duration of
             the study.

          -  Cotinine test is positive at Screening or Check-in (Day 2).

          -  Has poor peripheral venous access.

          -  Has donated or lost 450 mL or more of his blood volume (including plasmapheresis), or
             had a transfusion of any blood product within 30 days prior to Day 1.

          -  Has a Screening or Check-in (Day -2) abnormal (clinically significant)
             electrocardiogram (ECG). Entry of any patient with an abnormal (not clinically
             significant) ECG must be approved, and documented by signature by the principal
             investigator.

          -  Has abnormal Screening or Day -2 laboratory values that suggest a clinically
             significant underlying disease or with the following lab abnormalities: alanine
             aminotransferase and/or aspartate aminotransferase >1.5 times the upper limit of
             normal.

          -  Has had cerebrospinal fluid (CSF) collection performed within 30 days prior to
             Check-in (Day -2).

          -  Has taken any selective serotonin reuptake inhibitor (SSRIs), selective norepinephrine
             reuptake inhibitors (SNRIs), or monoamine oxidase inhibitors, antipsychotics,
             tricyclic antidepressants, or mood stabilizers within the last year prior to
             Screening.

          -  Has a known hypersensitivity to the anesthetic or its derivatives used during CSF
             collection, or any medication used to prepare the area of lumbar puncture.

          -  Has significant vertebral deformities (scoliosis or kyphosis) which, in the opinion of
             the investigator, may interfere with lumbar puncture procedure.

          -  Has a history of clinically significant back pain and/or injury.

          -  Has local infection at the puncture site.

          -  Has a history of significant bleeding or coagulation disorder and/or low platelet
             levels (<130x10^9/L) or increased international normalized ratio (INR) (>1.3) at
             Screening.

          -  Answers positive to any suicidal ideation and/or suicidal behavior questions during
             administration of the Columbia-Suicide Severity Rating Scale.

          -  Has an orthostatic blood pressure drop of ≥20 mm Hg (based on the drop between supine
             and standing [3 minutes] systolic blood pressure) at Screening or Check-in (Day -2).

          -  Has abnormal Screening or Day -2 vital signs: resting systolic blood pressure ≤90 or
             ≥140 mm Hg or a resting diastolic blood pressure ≤50 or ≥90 mm Hg in supine position;
             resting pulse or heart rate (as read on ECG) <45 bpm or >100 bpm. No more than 2
             repeat measurements.

          -  Exercises extensively in his normal life (e.g., marathon running, triathlon, physical
             sports at a contest level etc).