A Study of TAK-994 in Adults With Type 1 and Type 2 Narcolepsy

Exclusion Criteria

• •1. Has a risk of suicide according to endorsement of Item 4 or 5 of the screening/baseline visit Columbia suicide severity rating scale (C-SSRS) or has made a suicide attempt in the previous 12 months.
• •2. Is an excessive (\>600 mg/day) caffeine user 1 week before to the study screening.
• •3. Has a history of cancer (except carcinoma in situ that has been resolved without further treatment or basal cell skin cancer); past or current epilepsy, seizure; a lifetime history of major psychiatric disorder other than depression or anxiety; a clinically significant history of head injury or head trauma; a history of cerebral ischemia, transient ischemic attack, intracranial aneurysm, or arteriovenous malformation; known coronary artery disease, a history of myocardial infarction, angina, cardiac rhythm abnormality, or heart failure; or current or recent (within 6 months) gastrointestinal disease expected to influence the absorption of drugs. Any history of Roux-en-Y gastric bypass is considered exclusionary and any other surgical intervention that may influence the absorption of drugs should be discussed and approved by the sponsor or designee before enrolling the participants.
• •4. Has a medical disorder, other than narcolepsy, associated with EDS. This includes clinically significant moderate to severe obstructive sleep apnea and/or with or without treatment with mandibular advanced device hypoglossal nerve stimulation and/or positive airway pressure (PAP) therapy) and/or restless legs syndrome (RLS)/periodic limb movement disorder that has a significant impact on daytime sleepiness. This is evidenced by a clinical history of sleep apnea syndrome (loud snoring with observed respiratory pauses in the absence of nPSG) and/or RLS causing historical sleep onset/maintenance insomnia with resultant insufficient sleep. Or any as evaluated during the clinical interview at screening. pPast PSG data demonstrating any of the following sleep disturbances: apnea Hypopnea Index ≥15 or apnea index ≥10, an oxygen saturation of \<80 for \>10 seconds, periodic leg movement arousal index of ≥15/h) or as evaluated on interview at the time of screening. Asshould be considered exclusionary unless, based on a clinical evaluation by the investigator, a meaningful change in clinical status has occurred that would impact the results. Because nPSG data is obtained on Day -2, subjects may fail screening if criteria are not meet on the Day -2 nPSG.
• •5. Has a usual bedtime later than 2400 (12:00 AM, midnight) or an occupation requiring nighttime shift work or variable shift work within the past 6 months or travel within more than 3 time zones, within 14 days before Study Day -2.
• •6. Has a 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 portions of the study. Participants undergoing optional CSF collection.
• •7. Has a local infection at the puncture site.
• •8. Has developed signs of lumbar radiculopathy, including lower extremity pain and paresthesia.
• •9. Has any known focal neurological deficit that might suggest an increase in intracranial pressure.