Clinical trial: A Study of TAK-994 in Adults With Type 1 and Type 2 Narcolepsy (NCT04096560)

Eligibility criteria:
Inclusion Criteria:

          1. Has a diagnosis of narcolepsy type 1 (NT1) (Parts A-C) or NT2 (Part D) by
             polysomnography (PSG)/ multiple sleep latency test (MSLT) performed within the past 10
             years meeting the minimal acceptable criteria for the proper performance of the
             PSG/MSLT as outlined by the International Classification of Sleep Disorders, 3rd
             edition criteria.

          2. The participant's Epworth Sleepiness Scale (ESS) score must be greater than or equal
             to (>=) 10 at Day -1.

          3. Must be willing to discontinue all medications used for the treatment of NT1/NT2.

          4. The human leukocyte antigen (HLA) genotype: Part A: should test positive for human
             leukocyte antigen (HLADQB1)* 06:02 (PARTs A-C)- (positive results for either
             homozygous or heterozygous alleles will be considered "positive" and acceptable).
             However, if the HLA test is negative (i.e. negative for the heterozygous allele) and
             the PI feels strongly that the participant has narcolepsy with cataplexy (NT1) then a
             discussion should be initiated between the PI and the sponsor or designee about the
             advisability of doing a spinal tap to determine the participant's cerebrospinal fluid
             (CSF) orexin-1 (OX-1) level. If the CSF result shows the orexin 1 (OX-1) concentration
             is either less than or equal to<110 pg/mL, or less than one-third of mean values
             obtained in normal participants with the same standardized assay, then the diagnosis
             of NT1 is established allowing the participant to be enrolled and randomized, If the
             CSF OX-1 concentration is >110 pg/mL then the participant will not be allowed to
             continue in the study .

          5. For Parts A, B, and C, during the screening period, participant, must have >=4 partial
             or complete episodes of cataplexy/week (WCR), and >=4 partial or complete episodes of
             cataplexy/week during the screening period when off of anticataplexy medications,
             averaged over 2 weeks (14 consecutive days) minimum. WCR recording taken during
             following period will be considered for study eligibility: after the participant has
             stopped taking anticataplexy medications for at least 7 days (minimum 7-day washout)
             and study Day -2.

        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.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 65 Years

Patient description (medical language): A 25-year-old woman comes to the clinic with her roommate.  The roommate says that the patient has twice fallen asleep while they were talking.  The patient has regularly fallen asleep in the afternoon while reading or watching television but typically feels refreshed after a brief nap.  She also reveals that she sometimes hears a voice prior to falling asleep.  She also complains of some episodes of clumsiness that cause her to drop objects or fall. MSLT showed that the sleep latency was less than 8 min and that the patient enters rapid eye movement (REM) sleep almost immediately.

Patient description (patient's own words): I brought my roommate to the clinic because she kept falling asleep when we were having a conversation. We're both 25 and usually healthy girls. She usually takes a nap in the afternoon while reading or watching TV, but usually, she is quite energetic afterward. She told me that she sometimes hears a voice before falling asleep. How weird! And sometimes she's the clumsiest! She keeps dropping all her stuff. The doctor did a sleeping test and she found out that it takes her less than 8 min to fall asleep.

Does the patient match the trial criteria? Entailment