Study to Determine D-amino Acid Oxidase Brain Enzyme Occupancy of TAK-831 After Single-dose Oral Administration

The purpose of this study is to determine the relationship between TAK-831 dose, plasma exposure, extent and duration of brain D-amino acid oxidase (DAO) enzyme occupancy following single oral dosing of TAK-831 in healthy participants.

The drug being tested in this study is called TAK-831. TAK-831 is a highly selective and potent inhibitor of DAO, a peroxisomal enzyme active towards neutral D-amino acids which potentially effects cerebellar dysfunction. This study will look at the relationship between TAK-831 plasma exposure and the extent and duration of brain DAO enzyme occupancy after single oral dosing of TAK-831 in healthy male participants using \[18F\]PGM299 radioactive tracer injection and PET imaging.

The study will enroll up to 22 participants in two different sets. Up to 16 participants will be enrolled in Set A. Within that total, up to 5 dose levels of TAK-831 may be evaluated, with up to 6 participants per dose level, although typically, there will be 2 to 3 participants per dose level. All participants in Set A will also receive up to 3 doses of \[18F\]PGM299. Up to 6 participants will be enrolled in Set B. All participants in Set B will be assigned to single treatment group to receive 2 doses of \[18F\]PGM299.

All participants in Set A will be asked to take single oral dose of TAK-831 suspension on Day 1. In Set A, each of the participant will receive a maximum of 3 PET scans with \[18F\]PGM299; 1 at baseline 2 following a single oral dose of TAK-831 on Days 1 and 2. In Set B, each of the participant will receive 2 PET scans with \[18F\]PGM299 on Days 1 and 10. Set B will be conducted after the confirmation of blockade of \[18F\]PGM299 binding by TAK-831 in 2 to 4 participants of Set A.

This multi-center trial will be conducted in the United Kingdom. The overall time to participate in this study is 62 days. Participants in Set A will make 4 visits to the clinic, and participants in Set B will make 3 visits to the clinic and all will be contacted by telephone on Day 15 (Set A) and Day 12 (Set B) of treatment period for a follow-up assessment.

Eligibility Criteria:
Inclusion Criteria:

1. Is capable of understanding and complying with protocol requirements.
2. Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. Is in good health as determined by physical examination, electrocardiogram (ECG), and laboratory evaluations.
4. Is a healthy male aged 25 to 55 years, inclusive, at the time of informed consent and first injection of the PET tracer.
5. Weighs at least 45 kilogram (kg) and has a body mass index (BMI) from 18.0 to 30.0 kilogram per square meter (kg/m\^2), inclusive, at Screening.
6. Agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 90 days after last dose.

Exclusion Criteria:

1. Has received any investigational compound or device within 3 months or 5 half-lives, whichever is longer, prior to Check-in for Screening.
2. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (example, spouse, parent, child, sibling) or may consent under duress.
3. Has uncontrolled, clinically significant (CS), neurologic (including seizure disorder), cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal (GI), urologic, immunologic, or endocrine disease or psychiatric disorder, or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results.
4. Has a known hypersensitivity to any component of the formulation of TAK-831 or related compounds, or to \[18 F\]PGM299 or to any of its components.
5. Has a positive urine or breath test result for drugs of abuse (defined as any illicit drug use), ethanol (alcohol), or cotinine at Screening, Check-in for Baseline Imaging/Confinement Period 1, or Check-in for the Treatment/Confinement Period 2 (Day -1) for a participant participating in Set A or at Screening, Check-in for Tracer TEST PET Imaging/Confinement Period 1, or Check-in for RE-TEST PET Imaging/Confinement Period 2 for a participant participating in Set B.
6. Has a history of drug abuse (defined as any illicit drug use) or a history of ethanol (alcohol) abuse within 1 year prior to the screening visit or is unwilling to agree to abstain from ethanol (alcohol) and drugs throughout the study.
7. Has taken any medication, supplements, or food products during the time periods listed in the excluded medications and dietary products table.
8. Intends to donate sperm during the course of this study or for 90 days after the last dose of study medication.
9. Has evidence of current cardiovascular, central nervous system, hepatic, or hematopoietic disease; renal, metabolic or endocrine dysfunction; serious allergy, asthma, hypoxemia, hypertension, or allergic skin rash; or 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-831 or a similar drug in the same class, which might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease and cardiac arrhythmias.
10. Has current or recent (within 6 months) GI disease that would be expected to influence the absorption of drugs (that is, a history of malabsorption), any surgical intervention known to impact absorption (example, bariatric surgery or bowel resection), esophageal reflux, peptic ulcer disease, erosive esophagitis, or frequent (more than once per week) occurrence of heartburn.
11. Has a history of cancer, except basal cell carcinoma that has been in remission for at least 5 years prior to Day 1.
12. Has a positive test result for hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) antibody (HCAB), or human immunodeficiency virus (HIV) infection at Screening.
13. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 44 days prior to Check-in for Confinement Period 1. Cotinine test is positive at Screening, or Check-in for Confinement Period 1, or Confinement Period 2.
14. Has poor peripheral venous access.
15. Has an abnormal Allen's test in either upper extremity.
16. Has donated or lost 450 milliliter (mL) or more of his blood volume (including plasmapheresis), or had a transfusion of any blood product within 90 days prior to Confinement Period 1.
17. Has an abnormal CS ECG at Screening, Check-in for Confinement Period 1, or at Check-in for Confinement Period 2. Entry of any participant with an abnormal (not clinically significant \[NCS\]) ECG must be approved and documented by signature of the coordinating investigator or delegate.
18. Has a supine blood pressure outside the ranges of 100 to 140 millimeter of mercury (mm Hg) for systolic and 50 to 90 mm Hg for diastolic, confirmed with 1 repeat testing within a maximum of 30 minutes, at the Screening Visit, Check-in for Confinement Period 1, or Confinement Period 2.
19. Has a resting heart rate outside the range of 50 to 90 beats/minute, confirmed with 1 repeat testing within a maximum of 30 minutes, at the Screening Visit, Check-in for Confinement Period 1, or Confinement Period 2.
20. Has a Fridericia's Correction Formula (QTcF) - QTcF interval greater than (\>) 450 millisecond (msec) or PR outside the range of 120 to 220 msec, confirmed with 1 repeat testing within a maximum of 30 minutes, at the Screening Visit, Check-in for Confinement Period 1, or Confinement Period 2.
21. Has abnormal Screening laboratory values that suggest a CS underlying disease or the following laboratory abnormalities: Alanine Aminotransferase (ALT) and/or Alanine serum transaminase AST \>1.5\*upper limit of normal (ULN).
22. Has a risk of suicide according to the investigator's clinical judgment (example, per Columbia-Suicide Severity Rating Scale \[C-SSRS\]) or has made an attempt in the previous 6 months.
23. Has had a seizure or convulsion (lifetime), including absence seizure and febrile convulsion.
24. In the opinion of the investigator, is unlikely to comply with the protocol or is unsuitable for any other reason.
25. Has had previous exposure to ionizing radiation such that, in combination with the exposure from this study, their exposure will be \>10 millisievert (mSv) for the previous year.
26. Has a contraindication to medical resonance imaging (MRI) based on the standard MRI screening questionnaire. Contraindications include ferromagnetic foreign bodies (example, shrapnel, ferromagnetic fragments in the orbital area), certain implanted medical devices (example, aneurysm clips, cardiac pacemakers) or claustrophobia.
27. Has findings on screening brain MRI scan that will potentially compromise participant safety or the scientific integrity of the study data, if the participant were to participate in this study.
28. Has prolonged prothrombin time (PT) or activated partial thromboplastin time (PTT) or reduced platelet count (less than \[\<\] 100\*10\^9/Liter \[L\]).