Narcolepsy Type 1, Narcolepsy type 2
Conditions
Interventions
investigational material(s)
Generic name etc : TAK-994
INN of investigational material : -
Therapeutic category code : 117 Psychotropic agents
Dosage and Administration for Investigational material :
Sponsors
Takeda Pharmaceutical Company Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has a diagnosis of narcolepsy type 1 (NT1) (Part 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 sInternational 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 OX-1 concentration is either less than or equal to110 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
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 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 met on the Day -2 nPSG. 5. Has a usual bedtime later than 24:00 (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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1.Safety: Part A: Number of Participants who Experience at least 1 Treatment Emergent Adverse Events (TEAEs) During the Study Time Frame: First dose of study treatment to end of study follow-up (up to Day 35) in Part A An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an AE with an onset that occurs after receiving study drug. 2.Safety: Part A: Number of Participants who Meet the Markedly Abnormal Value (MAV) Criteria for Safety Laboratory Tests at least Once Postdose During the Study Time Frame: First dose of study treatment to end of study follow-up (up to Day 35) in Part A Standard safety laboratory values (serum chemistry, hematology, and urine analysis) were collected and compared to pre-specified criteria for MAVs. MAVs criteria: Erythrocytes (10^12/L: 1.2*upper limit of normal (ULN); Hemoglobin grams per litre(g/L): 1.2xULN; Hematocrit voltage/volts (V/V): 1.2*ULN; Platelets(10^9/L): 600; Leukocytes (10^9/L): 1.5*ULN; Alanine Aminotransferase units/litre (U/L): >3*ULN, Aspartate Aminotransferase (U/L): >3*ULN; Bilirubin micromoles/litre (micromol/L): >1.5*ULN; Alkaline Phosphatase (U/L): >3*ULN; Gamma Glutamyl Transferase (U/L): >3*ULN; Albumin (g/L): 1.2*ULN; Glucose millimoles/litre (mmol/L): 19.4; Calcium(mmol/L): 2.77; Creatinine (micromol/L): >1.5*ULN; Urea (mmol/L): >10.7; Sodium (mmol/L): 150; Potassium(mmol/L): 5.3. 3.Safety: Part A: Number of Participants who Meet the MAV Criteria for Vital Sign Measurements at least Once Postdose During the Study Time Frame: First dose of study treatment to end of study follow-up (up to Day 35) in | — |
Secondary
| Measure | Time frame |
|---|---|
| 1.Pharmacokinetics: Part A: Cmax: Maximum Observed Plasma Concentration After Single Dose of TAK-994 at Day 1 Time Frame: Pre-dose and at multiple time points (Up to 14 hours) post-dose at Day 1 in Part A 2.Pharmacokinetics: Part A: Tmax: Time of First Occurrence of Cmax After Single Dose of TAK-994 at Day 1 Time Frame: Pre-dose and at multiple time points (Up to 14 hours) post-dose at Day 1 in Part A 3.Pharmacokinetics: Part A: AUC(0-last): Area Under the Concentration-time Curve from Time 0 to Time of the Last Quantifiable Concentration After Single Dose of TAK-994 at Day 1 Time Frame: Pre-dose and at multiple time points (Up to 24 hours) post-dose at Day 1 in Part A 4.Pharmacokinetics: Part A: Cmax: Maximum Observed Plasma Concentration After Multiple Doses of at Days 28 Time Frame: Pre-dose and at multiple time points (Up to 14 hours) post-dose at Day 28 in Part A 5.Pharmacokinetics: Part A: Tmax: Time of First Occurrence of Cmax After Multiple Doses of at Day 28 Time Frame: Pre-dose and at multiple time points (Up to 14 hours) post-dose at Day 28 in Part A 6.Pharmacokinetics: Part A: AUC(0-t): Area Under the Concentration-time Curve from Time 0 to Time tau Over a Dosing Interval of TAK-994 at Day 28 Time Frame: Pre-dose and at multiple time points (Up to 14 hours) post-dose at Day 28 in Part A 7.Efficacy: Parts B and C: Change From Baseline in the Epworth Sleepiness Scale (ESS) Total Score to Week 8 Time Frame: Baseline and Week 8 (Day 56) in Parts B and C The ESS is a subjective, self-administered, validated scale (scored 0 to 3) to respond to each of the 8 questions of daily life that asks them how likely they are to fall asleep in those situations. The scores are summed to give an overall score of 0 to 24. Higher scores indicate stronger subjective daytime sleepiness, and scores below 10 are considered to be within the normal range. MMRM was used for analysis. 8.Efficacy: Parts B and C: Change From Baseline in Weekly Cataplexy Rate (WCR) at Week 8 Tim | — |
Countries
Europe, Japan, United States, China
Outcome results
None listed