Effects of TAK-063 on Preventing Ketamine-Induced Brain Activity Changes as Well as Psychotic-Like Symptoms in Healthy Male Adults
Condition: Ketamine-Induced Brain Activity Changes; Psychotic-like Symptoms
MeSH terms: Mental Disorders; Psychotic Disorders
Intervention: Ketamine; TAK-063; TAK-063 Placebo
Intervention description: Ketamine intravenous administration.; TAK-063 tablets; TAK-063 placebo-matching tablets
Intervention MeSH terms: Ketamine
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 27.0
Sex: Male
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Drug therapy

Summary:

      The purpose of this study is to determine whether ketamine-induced brain activity changes are
      modulated by TAK-063 administration using neuroimaging battery tests.
    

Eligibility criteria:

        Inclusion Criteria:

          1. In the opinion of the investigator, participant is capable of understanding and
             complying with protocol requirements.

          2. The participant or, when applicable, the participant's legally acceptable
             representative signs and dates a written, informed consent form and any required
             privacy authorization prior to the initiation of any study procedures.

          3. Is a healthy adult male.

          4. Speaks English as their first language.

          5. Is aged 18 to 45 years, inclusive, at the time of informed consent and first dose of
             study drug.

          6. Weighs at least 50 kg and has a body mass index (BMI) between 18 and 32 kilogram per
             metre square (kg/m^2), inclusive at Screening.

          7. A male participant who is nonsterilized and sexually active with a female partner of
             childbearing potential agrees to use adequate contraception from signing of informed
             consent throughout the duration of the study and for 12 weeks after last dose.

          8. Has a normal magnetic resonance imaging (MRI) scan and electroencephalogram (EEG)
             measurement at Screening.

        Exclusion Criteria:

          1. Has received any investigational compound or ketamine within 30 days prior to Day 1 of
             Period 1.

          2. Has received TAK-063 in a previous clinical study or as a therapeutic agent.

          3. Is an immediate family member, study site employee, or in a dependent relationship
             with a study site employee who is involved in the conduct of this study (e.g., spouse,
             parent, child, sibling) or may consent under duress.

          4. Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary,
             hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease,
             or psychiatric disorder, or other abnormality (including MRI or EEG), which may impact
             the ability of the participant to participate or potentially confound the study
             results.

          5. Has a known hypersensitivity to any component of the formulation of TAK-063 or
             ketamine.

          6. Has a contraindication for ketamine.

          7. Has a positive result for drugs or alcohol at Screening or Check-in (Day -1 of Period
             1).

          8. Has a history of drug or alcohol abuse or dependence (as defined by Diagnostic &
             Statistical Manual of Mental Disorders, fourth Edition [DSM-IV]) within 1 year prior
             to the screening visit or is unwilling to agree to abstain from alcohol and drugs
             throughout the study.

          9. Has taken any excluded medication, supplements, or food products listed in the
             Excluded Medications and Dietary Products.

         10. Has evidence of current cardiovascular, central nervous system (CNS), hepatic,
             hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious
             allergy, asthma hypoxemia, hypertension, seizures, or allergic skin rash. There is any
             finding in the participant's medical history, physical examination, or safety
             laboratory tests giving reasonable suspicion of a disease that would contraindicate
             taking TAK-063 or ketamine or a similar drug in the same class, or that might
             interfere with the conduct of the study. This includes, but is not limited to, peptic
             ulcer disease, seizure disorders, and cardiac arrhythmias.

         11. Has current or recent (within 6 months) gastrointestinal disease that would be
             expected to influence the absorption of drugs (ie, a history of malabsorption,
             esophageal reflux, peptic ulcer disease, erosive esophagitis frequent [more than once
             per week] occurrence of heartburn, or any surgical intervention [e.g.,
             cholecystectomy]).

         12. Has a history of cancer, except basal cell carcinoma which has been in remission for
             at least 5 years prior to Day 1 of Period 1.

         13. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C
             antibody (HCV), or a known history of human immunodeficiency virus infection at
             Screening.

         14. 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 -1 of Period 1) or cotinine test is positive at Screening or Check-in
             (Day -1 of Period 1).

         15. Has poor peripheral arterial/venous access or recent wrist trauma.

         16. Has donated or lost 450 mL or more of his or her blood volume (including
             plasmapheresis), or had a transfusion of any blood product within 3 months prior to
             Day 1 of Period 1.

         17. Has a Screening and/or Check-in (Day -1 of Period 1) abnormal (clinically significant)
             electrocardiogram (ECG). Participant has a supine blood pressure outside the ranges of
             90 to 140 mm Hg for systolic and 50 to 90 mm Hg for diastolic, if out of range may be
             repeated once for eligibility determination at the Screening Visit or Check-in (Day -1
             of Period 1).

         18. Has a resting heart rate outside the range 50 to 90 beats per minute (bpm), if out of
             range may be repeated once for eligibility determination at the Screening Visit and/or
             Check-in (Day -1 of Period 1).

         19. Has a QT interval with Fridericia correction method (QTcF) greater than (>) 430
             milliseconds (ms) or PR outside the range 120 to 220 ms, if out of range may be
             repeated once for eligibility determination within a maximum of 5 minutes, at the
             Screening Visit and/or Check-in (Day -1 of Period 1).

         20. Has abnormal Screening laboratory values that suggest a clinically significant
             underlying disease or participant with the following lab abnormalities: alanine
             aminotransferase (ALT) and/or aspartate aminotransferase (AST) >1.5 upper limit of
             normal (ULN).

         21. Has a history of Axis I/II mental disorders according to DSM-IV Axis I/II such as
             depression, anxiety disorders, bipolar disorder, attention deficit/hyperactivity
             disorder (ADHD), autism spectrum disorders, anorexia nervosa, bulimia nervosa, and
             schizophrenia.

         22. Has a history of head injury or trauma.

         23. Has any condition that would prevent an MRI from accurately or safely being performed
             (e.g., claustrophobia, cardiac pacemaker, metallic implants or clips), as verified per
             study site's standard MRI assessment questionnaire.

         24. Has a risk of suicide according to the Investigator's clinical judgment (e.g., per
             Columbia-Suicide Severity Rating Scale [C-SSRS]) or has made a suicide attempt in the
             previous 6 months prior to Screening.