A Randomized, Double‑Blind, Placebo‑Controlled Study of TAK‑360 for Safety, Tolerability, and Efficacy in Adults with Narcolepsy Type 1 (Cataplexy)

The primary objective is to assess Safety and tolerability of TAK‑360 in patients with Narcolepsy with Cataplexy (NT1) based on the post‑treatment adverse event profile. Secondary objectives evaluate the drug’s impact on Excessive Daytime Sleepiness and cataplexy:

• Effect on sleep latency measured by the Multiple Sleep Latency Test.
• Effect on subjective sleepiness assessed by the Epworth Sleepiness Scale total score.
• Effect on cataplexy frequency as determined by weekly cataplexy rate.

Twenty‑three participants were enrolled. The cohort included adults aged 18–70 years, of both sexes, with a body mass index between 18 and 40 kg/m². All participants had a confirmed diagnosis of narcolepsy with cataplexy (NT1) according to ICSD‑3 criteria and met laboratory requirements (HLA‑DQB1*06:02 positivity or CSF hypocretin‑1 ≤110 pg/mL). Selection required written informed consent, ability to comply with trial procedures, and overall health deemed adequate based on clinical laboratory tests, physical examination, 12‑lead ECG, and vital signs. Participants also agreed to follow contraceptive requirements where applicable. No specific diet or physical‑activity restrictions were noted in the eligibility description.

The study is a randomized, double-blind, placebo-controlled Phase 4 trial evaluating the safety, tolerability, and efficacy of oral TAK‑360 in adults with Narcolepsy with Cataplexy. Approximately 92 participants will be screened, randomized to one of several dosing regimens of TAK‑360 or matching placebo, and followed for a total of 6 weeks of treatment plus a final end‑of‑study visit. The sequence of visits includes a screening visit for eligibility assessment, baseline assessments and first dose administration, scheduled follow‑up visits at weeks 2, 4, and 6 to monitor adverse events, perform laboratory safety tests, and assess efficacy endpoints, and an end‑of‑study visit after the last dose. The primary efficacy evaluation is the occurrence of at least one treatment‑emergent adverse event, defined as the primary endpoint. Secondary efficacy measures include changes from baseline in mean sleep latency on the MWT, Epworth Sleepiness Scale score, and weekly cataplexy rate at week 6. Participant involvement spans from the screening visit through the end‑of‑study assessment, approximately 8 weeks in total. Early termination may occur for serious adverse events, non‑compliance with protocol requirements, or voluntary withdrawal of consent. The trial enrollment period is planned from June 2026 to November 2027.

The investigational product TAK-360 is provided as a film-coated tablet for oral administration. Each tablet contains the active moiety N‑{(6R)‑7,7‑difluoro‑2‑[5‑fluoro‑4‑(2,4,6‑trifluorophenyl)‑1,2‑benzoxazol‑3‑yl]‑3‑oxo‑2,5,6,7‑tetrahydro‑3H‑pyrrolo[1,2‑c]imidazol‑6‑yl}methanesulfonamide. The prescribed dose is 0 mg per tablet, administered via the oral route in accordance with the study dosing schedule.

The control arm utilizes a matching placebo preparation containing the same excipients as the active tablet but without the active substance. The placebo is also supplied as a film‑coated tablet and is taken orally following the identical dosing schedule as the active product.

All study medication and placebo are to be taken as directed by the study protocol, with dosing frequency and timing recorded in the participant diary. Compliance is monitored through pill counts at each study visit and verification of dosing entries in the electronic case report form.

Efficacy will be assessed using three secondary endpoints in participants with Narcolepsy with Cataplexy. The primary efficacy measure is the change from baseline in mean sleep latency obtained with the Multiple Sleep Latency Test at Week 6. The second measure is the change from baseline in total score of the Epworth Sleepiness Scale at Week 6. The third measure is the weekly cataplexy rate (WCR) evaluated at Week 6.

Mean sleep latency will be recorded by performing the MWT under standardized laboratory conditions at screening and at the Week 6 assessment. Participants will complete the ESS questionnaire at the same visits, providing a patient‑reported measure of daytime sleepiness. WCR will be calculated from cataplexy episodes documented in daily diaries throughout the treatment period and summarized for the Week 6 interval.

All efficacy parameters will be analyzed by comparing the change from baseline between the TAK‑360 and placebo groups using appropriate statistical methods to determine treatment effect.