A Global, Phase 3, Multicenter, Open-Label Study to Assess the Long-Term Safety and Tolerability of NBI-1117568 in Adults with Schizophrenia

The primary objective of this study is to evaluate the long-term safety of **NBI-1117568** in adults with **schizophrenia**. This assessment is clinically relevant as it aims to characterize the **safety profile** and **tolerability** of the investigational compound during extended treatment periods, which is essential for determining the **risk-benefit ratio** in chronic psychiatric conditions requiring prolonged pharmacotherapy.

The secondary objective is to evaluate the long-term maintenance of effect of NBI-1117568 in adults with schizophrenia. This evaluation addresses the clinical need to assess sustained **therapeutic efficacy** over time, which is critical for managing a chronic disorder characterized by potential symptom recurrence and the necessity for continuous antipsychotic treatment.

This clinical trial enrolled a total of **545 participants** diagnosed with **schizophrenia**. The study population consisted of both **male and female** subjects. Participants were required to be between **18 and 65 years of age** at the time of enrollment, with direct rollover participants from a parent study maintaining this age requirement from their initial screening. The trial included individuals classified as **adults and elderly** populations. A **vulnerable population** was included in this study. The primary inclusion criterion specified that participants must have a primary diagnosis of schizophrenia. The sponsor did not provide detailed information regarding specific lifestyle considerations such as diet, physical activity, or habits of the trial participants.

This is a global, multicenter, open-label, Phase 3 clinical trial designed to evaluate the long-term safety and tolerability of NBI-1117568 in adults with schizophrenia. The study employs an open-label design, meaning that both participants and investigators are aware of the treatment being administered. The investigational medicinal product contains the active substance direclidine and is formulated as hard capsules for oral administration. The primary objective is to assess the long-term safety profile of NBI-1117568 in the target population through monitoring the occurrence of adverse events during the open-label treatment period.

Eligible participants must be adults aged 18 to 65 years with a primary diagnosis of schizophrenia. Direct rollover participants from parent studies must have met the age criteria at the time of screening for the parent study. The maximum treatment period for individual participants is 156 weeks. The estimated recruitment start date is October 30, 2025, with an estimated study completion date of January 16, 2032, reflecting the extended duration required to evaluate long-term safety outcomes in this chronic condition.

The study involves sequential visits throughout the treatment period to monitor safety and tolerability parameters. Participants will undergo regular assessments including clinical evaluations, laboratory tests, and adverse event monitoring at scheduled follow-up visits. The frequency and content of these visits are designed to capture comprehensive safety data over the extended treatment duration. An end-of-study visit will be conducted upon completion of the treatment period or upon early discontinuation. Participants may be withdrawn from the study based on predefined criteria, including the occurrence of unacceptable adverse events, withdrawal of consent, protocol violations, or investigator decision based on safety concerns.

The experimental medication evaluated in this clinical trial is **NBI-1117568**, which contains the active substance **direclidine**. Direclidine is also known by the synonyms Ethyl cis-2-[4-(1-methyl-1H-pyrazol-5-yl)piperidin-1-yl]-6-azaspiro[3.4]octane-6-carboxylate and HTL0016878. The active substance is of chemical origin. NBI-1117568 is manufactured by Neurocrine Biosciences Inc.

Two formulations of NBI-1117568 are utilized in this study, identified by the sponsor product codes MFS-1117568-103 and MFS-1117568-105. Both formulations are presented as **hard capsules** intended for **oral administration**. The **pharmaceutical form** is identical for both product codes, consisting of hard capsules suitable for oral use. The maximum treatment period for both formulations is 156 weeks.

The study is designed as an open-label trial to assess the long-term safety and tolerability of NBI-1117568 in adults with **schizophrenia**. Both formulations are classified as test products in this clinical trial. Neither formulation is designated as a **paediatric formulation**, and neither holds orphan drug designation for this indication.

The primary endpoint for this clinical trial is the occurrence of adverse events during the Open-Label Treatment Period. Safety will be monitored throughout the treatment period, which extends up to 156 weeks. The trial focuses on evaluating the long-term safety profile of direclidine (NBI-1117568) administered as hard capsules via oral route in adults diagnosed with schizophrenia. The assessment will capture all adverse events that occur during the open-label treatment phase to characterize the safety and tolerability of the investigational medicinal product over an extended duration of exposure.