A Study of TAK-951 in Healthy Adults

Exclusion Criteria

• •Any participant who meets any of the following criteria will not qualify for entry into the study:
• •1. The participant has participated in another investigational study within 4 weeks (or based on local regulations) or within 5 half-lives, whichever is longest, of the investigational product before the screening visit. The 4-week or 5 half-lives window will be derived from the date of the last dose and/or AE related to the study procedure in the previous study to the screening visit of the current study.
• •2. The participant is an employee of the sponsor or study site or immediate family member (e.g., spouse, parent, child, sibling) of the sponsor or study site.
• •3. The participant has a history of significant multiple and/or severe allergies (e.g., food, drug, latex allergy) or has had an anaphylactic reaction or significant intolerance to prescription or nonprescription drugs or food, as determined by the investigator.
• •4. The participant has a known hypersensitivity or contraindication to any component of TAK-951.
• •5. The participant has a positive pregnancy test or is lactating or breastfeeding.
• •6. The participant has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency antibody/antigen, at the screening visit.
• •7. The participant had major surgery or donated or lost 1 unit of blood (approximately 500 milliliters \[mL\]) within 4 weeks before the screening visit.
• •8. The participant is unable to refrain from or anticipates using any medications including herbal medicines beginning approximately 7 days before administration of the first dose of study drug, throughout the study until 2 days after discharge.
• •9. The participant is unable to refrain from or anticipates using marijuana or cannabis-containing products beginning approximately 7 days before administration of the first dose of study drug, throughout the study until after the last pharmacokinetic (PK) dose.
• •10. The participant has a history or presence of alcoholism or drug abuse within the past 2 years prior to dosing, or frequent or heavy use (i.e., near-daily) of medical or recreational cannabis in the past 3 months before screening, as determined by the investigator.
• •11. The participant drinks alcohol in excess of 7 drinks/week for women or 14 drinks/week for men (where 1 drink=5 ounces \[150 mL\] of wine or 12 ounces \[360 mL\] of beer or 1.5 ounces \[45 mL\] of hard liquor \[45% alcohol\]) within 3 months before screening.
• •12. The participant has a positive alcohol test or urine drug screen results at screening or check-in.
• •13. The participant has had a previous major psychiatric disorder.
• •14. The participant has a history or presence of:
• •* 3 or more incidences of vasovagal syncope within the last 5 years prior to screening; or
• •* A family history of unexplained sudden death or channelopathy; or
• •* Brugada syndrome (i.e., right bundle branch block \[RBBB\] pattern with ST-elevation in leads V1-V3); or
• •* Cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction, stroke, sick sinus syndrome, pulmonary congestion, symptomatic or significant cardiac arrhythmia, second-degree atrioventricular (AV) block type 2, third-degree AV block, prolonged QT interval with Fridericia correction method (QTcF) interval, hypokalemia, hypomagnesemia, or conduction abnormalities; or
• •* Risk factors for Torsade de Pointes (e.g., heart failure, cardiomyopathy, or family history of Long QT Syndrome); or
• •* Any clinically significant ECG findings or medical history including: long or short QTcF (over 450 milliseconds (msec) or less than 360 msec), bifascicular block or QRS ≥120 msec or PR interval \>210 msec at screening or Day 1 pre-Hour 0; or
• •* The participant has a documented history of sinus bradycardia (\<45 beats per minute \[bpm\]), sinoatrial block or sinus pause ≥3 seconds.
• •15. The participant has an average semirecumbent blood pressure (BP) less than (\<)90/60 millimeters of mercury (mm Hg) or \>140/90 mm Hg from screening to predose, inclusive. Any assessments on Day -1 that do not meet this criterion must be discussed with the medical monitor for approval.
• •16. The participant has an average semirecumbent heart rate (HR) (pulse) \<55 or \>100 bpm at any time point from screening to predose, inclusive. Participants with an average HR (pulse) \<55 bpm can be enrolled only with medical monitor approval. Any assessments after admission with an average HR (pulse) \<55 bpm at any time point, from Day -2 to predose (inclusive), will be left to the judgment of the investigator, unless HR (pulse) is \<50 bpm, which must be discussed with the medical monitor for approval.
• •17. The participant has orthostatic hypotension defined as a decrease in systolic blood pressure (SBP) ≥20 mm Hg or a decrease in diastolic blood pressure (DBP) ≥10 mm Hg at approximately 3 minutes of standing when compared with BP from the semirecumbent position at screening to predose assessments, inclusive. In asymptomatic participants, any assessments after screening that do not meet this criterion may be repeated after the participant has remained in the semirecumbent or supine position for 15 minutes. If the repeat assessment is exclusionary based on the above criterion, the participant will not be eligible. If the repeat assessment is not exclusionary, the participant will be eligible.
• •18. The participant has postural orthostatic tachycardia, defined as an increase of \>30 bpm or pulse \>120 bpm at approximately 3 minutes of standing, at screening to predose assessments, inclusive. Any assessments after screening that do not meet this criterion may be repeated with the participant remaining standing for up to a total of 5 minutes, provided that the participant remains asymptomatic. If the repeat assessment occurring within 5 minutes is exclusionary based on the above criterion, the participant will not be eligible. A confirmed orthostatic increase of \>30 bpm, but \<40 bpm, on 1 or more Day -1 assessments may not be considered exclusionary if not considered clinically significant by the investigator and the medical monitor. Such assessments must be discussed with the medical monitor before determination that the participant is eligible to proceed.
• •19. The participant has a known or suspected current coronavirus disease 2019 (COVID-19) infection or is at risk of COVID-19 infection as assessed by the investigator.