Evaluation of Long-term Safety and Tolerability of TAK-861 in Patients with Narcolepsy Type 1

The primary objective of this study is to evaluate the long-term **safety** and **tolerability** of TAK-861 in participants with Narcolepsy with Cataplexy (Narcolepsy Type 1). This is clinically relevant as it aims to ensure that the therapeutic use of TAK-861 is safe for prolonged periods, which is crucial for managing chronic conditions like narcolepsy.

Secondary objectives include:

• Assessing the effect of TAK-861 on excessive daytime sleepiness (EDS) as measured by the mean sleep latency from the Maintenance of Wakefulness Test (MWT).
• Evaluating the effect of TAK-861 on EDS using the Epworth Sleepiness Scale (ESS) total score.
• Assessing the effect of TAK-861 on cataplexy by measuring the weekly cataplexy rate (WCR).

The clinical trial involves a total of **170 participants** diagnosed with **Narcolepsy with Cataplexy (Narcolepsy Type 1)**. The study population includes both male and female subjects, with an age range encompassing adults and older adults. Participants were selected based on their completion of a controlled study with TAK-861, and enrollment was contingent upon the absence of clinical objections from the investigator. The trial does not include a vulnerable population. Lifestyle considerations such as diet, physical activity, or habits are not specified. The primary objective of the trial is to evaluate the long-term safety and tolerability of TAK-861.

The clinical trial is designed to evaluate the long-term safety and tolerability of **TAK-861** in participants diagnosed with **Narcolepsy with Cataplexy (Narcolepsy Type 1)**. This study is a Phase 2/3 long-term extension study, following a randomized, double-blind, controlled methodology. The trial is expected to commence on February 26, 2023, and conclude by February 28, 2028, with a maximum treatment period of 60 days for each participant. Participants eligible for inclusion must have completed a prior controlled study with **TAK-861** and have no clinical objections from the investigator regarding their enrollment.

The study involves a series of visits, beginning with a screening visit to confirm eligibility based on the inclusion criteria. Participants will then undergo regular follow-up visits to monitor the occurrence of any treatment-emergent adverse events (TEAEs), which is the primary endpoint of the study. Secondary endpoints include changes from baseline in the Maintenance of Wakefulness Test (MWT) mean sleep latency, Epworth Sleepiness Scale (ESS) total score, and Weekly Cataplexy Rate (WCR) using the patient-reported Cataplexy Diary. The end-of-study visit will assess the overall safety and tolerability of the treatment.

Participant involvement is expected to last for the duration of the treatment period, with conditions for early termination including the occurrence of significant adverse events or withdrawal of consent. The study will utilize **TAK-861** in tablet form, administered orally, with no specified maximum daily or total dose amount. The trial aims to provide comprehensive data on the long-term effects of **TAK-861** in managing symptoms associated with **Narcolepsy with Cataplexy (Narcolepsy Type 1)**.

The clinical trial involves the administration of the experimental medication **TAK-861**, which is formulated as a **tablet**. The active substance in TAK-861 is chemically synthesized and identified as N-{(2S,3R)-4,4-difluoro-1-(2-hydroxy-2-methylpropanoyl)-2-[(2,3',5'-trifluoro[1,1'-biphenyl]-3-yl)methyl]pyrrolidin-3-yl}ethanesulfonamide. The medication is administered orally. The trial is designed to evaluate the long-term safety and tolerability of TAK-861 in participants with selected central hypersomnia conditions. The maximum treatment period for TAK-861 is 60 days. The dosage is expressed in milligrams, although specific dosing amounts are not provided in the trial data. Participant compliance with the dosing schedule will be monitored throughout the study.

In this study, TAK-861 is the primary investigational product, and no additional non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are mentioned. The trial does not specify any maximum daily or total dose amounts, indicating that the dosing regimen may be flexible or determined based on individual participant needs. The trial is conducted under the sponsorship of Takeda Development Center Americas, Inc., and TAK-861 has been designated as an orphan drug, highlighting its potential use in treating rare conditions. The study does not include a pediatric formulation of the medication.

Efficacy in the clinical trial evaluating TAK-861 for selected central hypersomnia conditions will be assessed using several secondary endpoints. These include the change from baseline in the parent study in the Maintenance of Wakefulness Test (MWT) mean sleep latency, the change from baseline in the Epworth Sleepiness Scale (ESS) total score, and the change from baseline in the Weekly Cataplexy Rate (WCR) using the patient-reported Cataplexy Diary. These parameters will be measured to determine the impact of TAK-861 on sleep latency, daytime sleepiness, and cataplexy episodes, respectively. The assessments will be conducted at specified intervals throughout the trial to monitor changes over time. The data collected will be analyzed to evaluate the efficacy of TAK-861 in improving symptoms associated with central hypersomnia conditions.