The purpose of this study is to evaluate the safety and tolerability of administering a single intravenous (IV) infusion dose of TAK-925 to adult participants with idiopathic hypersomnia (IH).

The drug being tested in this study in participants with IH is called TAK-925. The study will have 2-treatment crossover groups. The study will evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of a single intravenous (IV) dose of Dose A in participants with IH.

The study will enroll 40 patients. Participants will be randomly assigned to one of the two treatment sequence groups as indicated below:

• TAK-925 + Placebo
• Placebo + TAK-925

On Day 1 of each treatment period, TAK-925 or placebo will be administered as a single 9-hour IV infusion.

The multicenter study will be conducted in the United States and Japan. The overall duration of treatment in this study is approximately 41 days including screening up to 28 days, confinement for 6 days and end of study follow up telephone call on Study Day 11.

Inclusion Criteria:

1. A diagnosis of IH, as defined by the International Classification of Sleep Disorders-3 (ICSD-3) as verified by a previous nocturnal polysomnography (nPSG) and multiple sleep latency test (MSLT) study performed within the last 10 years.
2. Onset of hypersomnia between 10 and 30 years of age.
3. Seven consecutive days of actigraphy supported by a sleep diary obtained prior to the nPSG (Study Day -2) shows an average nightly sleep duration of greater than or equal to (>=) 420 minutes during the participant's normal nocturnal sleep period.
4. nPSG (Study Day -2) demonstrates that participant does not have other comorbid sleep disorders or clinically significant nocturnal hypoxemia (oxygen saturation ≤80% for ≥5% of total sleep time) and that their Apnea-Hypopnea Index (AHI) is less than or equal to (<=) 10 per hour, their periodic limb movement arousal index (PLMAI) <=15/hour, and that their total sleep time is >=6.5 hours.
5. Participants taking medication for treatment of excessive daytime sleepiness (EDS) must be willing to discontinue medication prior to randomization into the study.
6. Body mass index (BMI) of 18 through 33 kilogram per square meter (kg/m^2) inclusive.
7. Epworth Sleepiness Scale (ESS) score >=11 at screening and on Day -2.
8. Blood pressure (BP) must be <140 mmHg (systolic) and <90 mmHg (diastolic) at screening and Study Day -2.

Exclusion Criteria:

1. Average nightly sleep duration is <=8 hours (480 minutes) and has insufficient sleep syndrome as evidenced by sleeping >2 hours/night more on "off-days" relative to "work days" as determined by actigraphy and sleep diary obtained prior to the nPSG (Study Day -2).
2. Positive urine screen for drugs of abuse and/or positive alcohol test at screening and Study Day -2.
3. Resting heart rate (HR) outside of the range of 40 to 90 beats pper minute (bpm) off stimulants.
4. Screening electrocardiogram (ECG) reveals a QT interval with Fridericia correction method >450 ms (men) or >470 ms (women).
5. Usual bedtime later than 24:00 (midnight) or an occupation requiring nighttime shift work or variable shift work within the past 6 months, or travel with significant jet lag within 14 days before Study Day -2.
6. History of a sleep disorder other than IH, based on interviews at the screening visit, such as obstructive sleep apnea (OSA), restless legs syndrome, or periodic limb movements of sleep (PLMS) associated with arousals.
7. Use of any over-the-counter (OTC) or prescription medications with stimulating properties within 7 days prior to dosing or 5 half-lives (whichever is longer) that could affect the evaluation of EDS or use of sodium oxybate within 3 months of screening.
8. Nicotine dependence that is likely to have an effect on sleep (e.g., a participant who routinely awakens at night to smoke) and/or an unwillingness to discontinue all smoking and nicotine use during the confinement portion of the study (Day -2 to Day 4).
9. Caffeine consumption of more than 600 mg/day for 7 days before Study Day 1 (1 serving of coffee is approximately equivalent to 120 mg of caffeine) and/or unwilling to discontinue all caffeine during the confinement portion of the study (Day -2 to Day 4).
10. Alcohol use that is likely to have an effect on sleep and/or an unwillingness to discontinue all alcohol use from 72 hours before check-in through discharge on Study Day 4.
11. History of epilepsy or seizures, including having had a single seizure or a history of childhood febrile seizures or has a clinically significant history of head trauma.
12. Answered "YES" on Questions 4 or 5 on the Suicidal Ideation subscale of the Columbia Suicide Severity Rating Scale (C-SSRS) at screening (defined period as 3 months prior to screening) or evidence of suicidal behavior within 6 months of screening as measured by the Suicidal Behavior subscale of the C-SSRS.
13. Diagnosis of major depressive disorder (DSM-5), within the past 6 months or Beck Depression Inventory II (BDI-II) total score of >16 at the screening visit.
14. History of cerebral ischemia, transient ischemic attack, intracranial aneurysm, or arteriovenous malformation.
15. Known coronary artery disease, a history of myocardial infarction, angina, cardiac rhythm abnormality, or heart failure.

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.