An [^11C]T-773 Positron Emission Tomography (PET) Study to Determine Phosphodiesterase10A Occupancy by TAK-063
Condition: Healthy Volunteers
Intervention: TAK-063; [^11C]T-773
Intervention description: TAK-063 tablets; [^11C]T-773 IV solution
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: Male
Minimum age: 20 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Drug therapy

Summary:

      The purpose of this study is to estimate phosphodiesterase 10A (PDE10A) occupancy in brain
      following a single dose of TAK-063.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Has never previously participated in a positron emission tomography (PET) study
             (lifetime).

          2. In the opinion of the investigator, the participant is capable of understanding and
             complying with protocol requirements.

          3. The participant, informed consent form and any required privacy authorization prior to
             the initiation of any study procedures.

          4. Is a healthy adult male, as determined by a physician based upon medical history and
             physical examination findings at Screening.

          5. Is aged 20 to 45 years, inclusive, at the time of informed consent.

          6. Weighs at least 50 kg and less than 100 kg and has a body mass index (BMI) between 18
             and 32 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 clinical laboratory evaluations (including clinical chemistry, hematology and
             complete urinalysis) within the reference range for the testing laboratory, unless the
             results are deemed not to be clinically significant (CS) by the investigator or
             sponsor at screening. Participants must have normal hemoglobin levels.

          9. Has a normal magnetic resonance imaging (MRI) scan or findings that are deemed not
             clinically significant at screening (the MRI scan may be performed on a day after
             other screening activities have been performed but before dosing).

        Exclusion Criteria:

          1. Has received any investigational compound within 90 days prior to Screening.

          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 dependant relationship
             with a study site employee who is involved in the conduct of this study (eg, 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, 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
             [^11C]T-773.

          6. Has a positive urine drug result for drugs of abuse or a positive breathalyzer test
             for alcohol at Screening or Day -1.

          7. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol
             abuse within 1 year prior to the screening visit or is unwilling to agree to abstain
             from alcohol until discharge from the Phase 1 unit and drugs throughout the study.

          8. Has taken any excluded medication, supplements, or food products listed in the
             Excluded Medications and Dietary Products table.

          9. Intends to donate sperm during the course of the study or within 12 weeks after last
             dose.

         10. Has evidence of current cardiovascular, central nervous system, 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 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. The participant, in the opinion of the investigator, 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 [eg, 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.

         13. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C
             antibody (HCV), human immunodeficiency virus (HIV) antibody/antigen, 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.

         15. Has poor peripheral arterial/venous access or recent arm or wrist trauma.

         16. Has donated or lost 450 mL or more of his blood volume (including plasmapheresis), or
             had a transfusion of any blood product within 3 months prior to Day 1.

         17. Has a Screening or Check-in (Day -1) abnormal (clinically significant)
             electrocardiogram (ECG).

         18. 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 within a maximum of 5 minutes, at the Screening Visit or Check-in (Day
             -1).

         19. Has a resting heart rate outside the range 45 to 90 beats per minute (bpm), if out of
             range may be repeated once for eligibility determination within a maximum of 5
             minutes, at the Screening Visit or Check-in (Day -1).

         20. Has an increase in pulse of ≥30 beats per minute or an increase in pulse ≥120 beats
             per minute within 3 minutes of standing at Screening.

         21. Has a decrease of ≥20 mm Hg in systolic blood pressure or a decrease of ≥10 mm Hg in
             diastolic blood pressure within 3 minutes of standing at Screening.

         22. Has a QT interval with Fridericia correction method (QTcF) >430 ms or PQ interval
             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 or Check-in (Day
             -1) Visit.

         23. 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 the upper limits
             of normal.

         24. Has had administration of radioactive substances or exposure to significant radiation
             (eg, serial x-ray or computed tomography [CT] scans, barium meal) within the past 12
             months prior to Day 1 predose.

         25. Has any condition that would prevent an MRI from accurately or safely being performed
             (eg, claustrophobia, cardiac pacemaker, metallic implants or clips)

         26. Has any condition that would prevent the performance of a safe or accurate PET scan.

         27. Has any clinically significant MRI finding that in the opinion of the investigator
             would exclude the participant.

         28. Is unwilling to refrain from strenuous exercise from 120 hours before Check-in (Day
             -1) until discharge from the Phase 1 unit.

         29. Has a risk of suicide according to the Investigator's clinical judgment (eg, per
             Columbia-Suicide Severity Rating Scale (C-SSRS) or has made a suicide attempt in the
             previous 6 months.

         30. Has abnormal international normalized ratio (INR) or activated prothrombin time (aPTT)
             or other risk of bleeding disorder.