Long-Term Safety Evaluation of Adjunctive Troriluzole in Patients with Obsessive Compulsive Disorder Unresponsive to SSRI, Clomipramine, Venlafaxine, or Desvenlafaxine

The primary objective of this study is to evaluate the long-term **safety** and tolerability of **troriluzole** as an adjunctive therapy in subjects with **Obsessive Compulsive Disorder** (OCD) who have had an inadequate response to selective serotonin reuptake inhibitors (SSRIs), clomipramine, venlafaxine, or desvenlafaxine treatment. This is clinically relevant as it addresses the need for effective treatment options for patients with OCD who do not respond adequately to standard pharmacological therapies. The study aims to provide insights into the safety profile of troriluzole over an extended period, which is crucial for understanding its potential role in the management of treatment-resistant OCD.

The clinical trial involves a total of **1157 participants** diagnosed with **Obsessive Compulsive Disorder** (OCD). The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on their completion of prior studies BHV4157-302 or BHV4157-303, and their medical stability as determined by the investigator. The trial includes individuals who have had an inadequate response to treatments such as SSRIs, clomipramine, venlafaxine, or desvenlafaxine. The study population is characterized by a requirement for medically stable individuals, as assessed through medical history, physical examination, laboratory tests, and electrocardiogram results. Additionally, women of childbearing potential and fertile men with female partners of childbearing potential are required to use highly effective birth control methods throughout the study. The trial also considers vulnerable populations, ensuring comprehensive safety and ethical standards are maintained.

The clinical trial is designed to evaluate the long-term safety and tolerability of **troriluzole** as an adjunctive therapy in subjects with **Obsessive Compulsive Disorder** (OCD) who have shown an inadequate response to selective serotonin reuptake inhibitors (SSRIs), clomipramine, venlafaxine, or desvenlafaxine. This is a multicenter, open-label study, which means that both the researchers and participants know which treatment is being administered. The trial is expected to run until February 14, 2030, with recruitment having started on May 3, 2021. Participants will be involved in the study for a maximum treatment period of 144 weeks.

Study visits are structured to ensure comprehensive monitoring and data collection. The inclusion visit, or screening, will determine eligibility based on criteria such as completion of prior studies BHV4157-302 or BHV4157-303, medical stability, and agreement to use effective contraception methods. Follow-up visits will occur regularly to assess safety and tolerability, with primary endpoints focusing on the frequency of serious adverse events (SAEs), adverse events (AEs) leading to discontinuation, AEs related to the study medication, and clinically significant laboratory abnormalities. The end-of-study visit will conclude the participant's involvement, ensuring all safety assessments are completed.

Participants may be withdrawn from the study early if they experience significant adverse effects, fail to adhere to the study protocol, or if the investigator determines that continued participation is not in the participant's best interest. The study employs a robust methodology to ensure the collection of reliable data, contributing to the understanding of **troriluzole**'s safety profile in the treatment of OCD.

The clinical trial involves the administration of **Troriluzole**, an investigational medication developed by Biohaven Pharmaceuticals, Inc. **Troriluzole** is provided in a **capsule** form and is intended for oral administration. The trial includes two dosing regimens of **Troriluzole**. The first regimen involves a maximum daily dose of 140 mg, with a total maximum dose of 280 mg over the course of the treatment period. The second regimen involves a maximum daily dose of 100 mg, with a total maximum dose of 200 mg. The treatment period for both regimens is set at 144 days. The active substance in **Troriluzole** is of chemical origin, and the medication is not formulated for pediatric use. The trial aims to assess the long-term safety and tolerability of **Troriluzole** as an adjunctive therapy in subjects with Obsessive Compulsive Disorder (OCD) who have shown an inadequate response to standard treatments such as SSRIs, clomipramine, venlafaxine, or desvenlafaxine.

In addition to the experimental medication, participants in the study may continue to receive standard-of-care therapy as deemed necessary by their healthcare providers. This may include the aforementioned SSRIs, clomipramine, venlafaxine, or desvenlafaxine, which are commonly used in the management of OCD. The trial does not utilize a placebo or comparator treatment. Compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen. Participants' adherence to the medication schedule will be assessed through regular follow-ups and medication counts, ensuring the integrity of the trial data.

Efficacy in the clinical trial will be assessed through the primary endpoint of safety and tolerability. This will be evaluated by monitoring the frequency of unique subjects experiencing serious adverse events (SAEs), adverse events (AEs) leading to discontinuation, AEs judged to be related to the study medication, and clinically significant laboratory abnormalities. These parameters will be observed over the course of treatment with **troriluzole** in subjects with Obsessive Compulsive Disorder (OCD) who have had an inadequate response to selective serotonin reuptake inhibitors (SSRIs), clomipramine, venlafaxine, or desvenlafaxine treatment. The trial is designed as a long-term, open-label safety study, and the data collection will be conducted in a multicenter setting. The study aims to provide comprehensive safety data to support the use of **troriluzole** as an adjunctive therapy in this patient population.