Long-Term Evaluation of Safety, Tolerability, and Treatment Durability of ALKS 2680 in Patients with Narcolepsy Type 1 and Type 2

The primary objective of this study is to evaluate the **safety** and **tolerability** of ALKS 2680 in subjects diagnosed with narcolepsy. This is clinically relevant as it aims to ensure that the treatment is safe for long-term use in managing narcolepsy, a chronic sleep disorder characterized by excessive daytime sleepiness and sudden muscle weakness (cataplexy).

Secondary objectives include:

• To evaluate the safety and tolerability of ALKS 2680 in subjects with narcolepsy.
• To assess the efficacy and durability of the effect of ALKS 2680 for the treatment of excessive daytime sleepiness (EDS) in subjects with narcolepsy and the treatment of cataplexy in subjects with Narcolepsy Type 1 (NT1).

The clinical trial involves a total of **129 participants** diagnosed with **narcolepsy** Type 1 and Type 2. The study population includes both male and female subjects, with an age range that encompasses adults and adolescents. Participants were selected based on their completion of an ALKS 2680 eligible parent study, specifically ALKS 2680-201 or ALKS 2680-202, and their ability to comply with the study's protocol requirements. The trial includes a vulnerable population, indicating that special considerations are in place to ensure their safety and well-being. Participants are required to adhere to certain lifestyle considerations, including contraception guidance and medication discontinuation, as applicable. The trial aims to evaluate the safety and tolerability of ALKS 2680 in this specific population.

The clinical trial is designed to evaluate the **safety** and tolerability of **ALKS 2680** in subjects diagnosed with **narcolepsy** Type 1 and Type 2. This is an open-label, long-term extension study, which means that both the researchers and participants are aware of the treatment being administered, and it extends the duration of treatment for participants who have completed a prior study involving ALKS 2680. The trial is expected to run until December 31, 2027, with recruitment starting on June 1, 2025. Participants will be involved in the study for a maximum treatment period of 96 weeks.

The trial involves a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as previous participation in an ALKS 2680 study and the ability to comply with protocol requirements. Following the screening, participants will undergo regular follow-up visits to monitor treatment-emergent adverse events (TEAEs) and secondary endpoints, including clinical laboratory assessments, vital signs, safety electrocardiograms (ECGs), and changes in sleep-related measures. The end-of-study visit will conclude the participant's involvement, assessing the overall safety and efficacy of the treatment.

Participants are expected to adhere to specific lifestyle considerations and medication restrictions throughout the study. Conditions that may lead to early termination from the study include non-compliance with the protocol, withdrawal of consent, or any adverse events that, in the opinion of the investigator, warrant discontinuation of the treatment. The study aims to provide comprehensive data on the long-term effects of ALKS 2680, contributing to the understanding of its role in managing narcolepsy symptoms.

The clinical trial involves the administration of **ALKS 2680**, a chemical compound developed by Alkermes, Inc. The experimental medication is provided in the form of a **tablet** and is intended for oral administration. The study includes multiple dosing regimens of ALKS 2680, with the maximum daily doses ranging from 4 mg to 18 mg, depending on the specific formulation used. The maximum total dose for the treatment period, which spans up to 96 weeks, varies from 2,688 mg to 12,096 mg. The active substance in all formulations is chemically derived and is consistently referred to as ALKS 2680, with alternative identifiers including RDC-264177, RDC-264177-00, and CMG-177BFD00.

Throughout the trial, participant compliance with the dosing schedule is monitored to ensure adherence to the prescribed regimen. The study does not incorporate any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments. The primary objective of the trial is to evaluate the safety and tolerability of ALKS 2680 in subjects diagnosed with **narcolepsy** type 1 and type 2. The trial is designed as an open-label, long-term extension study, focusing on the durability of the treatment effect alongside safety assessments.

The efficacy of the investigational product **ALKS 2680** in the treatment of narcolepsy will be assessed through several secondary endpoints. These include changes in the mean sleep latency (MSL) on the Maintenance of Wakefulness Test (MWT) from baseline to Week 24, changes in the Epworth Sleepiness Scale (ESS) from baseline through the treatment period, and changes in the weekly cataplexy rate (WCR) from baseline through the treatment period for subjects with Narcolepsy Type 1 (NT1). These parameters will be measured at specified timepoints to evaluate the treatment's impact on sleep latency, daytime sleepiness, and cataplexy frequency.

The collection and analysis of these efficacy parameters will involve the use of validated scales and tests. The MWT will be employed to assess the ability to stay awake in a conducive environment, while the ESS will be used to evaluate the general level of daytime sleepiness. For NT1 subjects, the WCR will be monitored to determine the frequency of cataplexy episodes. These assessments will be conducted at baseline and at designated intervals throughout the treatment period to track changes and determine the efficacy of **ALKS 2680**.