Long-term Safety Evaluation of Iclepertin in Schizophrenia Patients Post-Completion of Phase III Trials

The primary objective of this clinical trial is to collect additional **safety** data for patients with cognitive impairment due to **schizophrenia** who have completed a 26-week treatment period with **Iclepertin** or a matching placebo in one of the Phase III clinical trials (trial # 1346-0011, 1346-0012, 1346-0013). This objective is clinically relevant as it aims to ensure the long-term safety of Iclepertin, a medication intended to address cognitive deficits associated with schizophrenia, thereby potentially improving patient outcomes and quality of life.

The clinical trial involves a total of **1113 participants** diagnosed with **schizophrenia**, specifically those with cognitive impairment who have completed a 26-week treatment period with Iclepertin or a matching placebo in a previous phase III clinical trial. The study population includes both male and female participants, aged 18 to 65 years, who are clinically stable outpatients. Participants were selected based on their completion of the parent trial and their ability to enter the extension trial within specified timeframes. The trial does not focus on a vulnerable population, and participants are required to have a study partner capable of understanding trial-related procedures. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data. The selection criteria ensure that participants are well-suited to provide additional safety data for the ongoing evaluation of Iclepertin's effects.

The clinical trial is designed as an open-label, single-arm extension study to evaluate the long-term safety of **Iclepertin** in patients with **schizophrenia** who have completed previous Phase III trials. The primary objective is to collect additional safety data in patients with cognitive impairment due to schizophrenia. Participants eligible for this trial are clinically stable outpatients diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). They must have completed a 26-week treatment period in a parent trial and enter the extension trial within specified timeframes post-treatment. The trial is expected to run from March 2022 to February 2026, with the maximum treatment period for participants being 12 months.

Study visits are structured to ensure comprehensive monitoring and data collection. The inclusion visit, or screening, confirms eligibility based on the principal inclusion criteria. Follow-up visits are scheduled to monitor the occurrence of treatment-emergent adverse events (TEAEs) and assess changes from baseline in Clinical Global Impressions – Severity (CGI-S) and hemoglobin levels. The end-of-study visit marks the conclusion of the participant's involvement, where final assessments are conducted. Participants are expected to remain in the study for up to 12 months unless conditions such as significant adverse events or withdrawal of consent necessitate early termination. The trial's design ensures rigorous safety monitoring while providing valuable data on the long-term effects of Iclepertin in the target population.

The clinical trial involves the administration of **Iclepertin**, an experimental medication developed by Boehringer Ingelheim International. Iclepertin is provided in the form of a **film-coated tablet** and is intended for oral administration. The dosage regimen for Iclepertin is a maximum daily dose of 10 mg, with a total maximum dose of 3650 mg over a treatment period of up to 12 months. The active substance, Iclepertin, is of chemical origin and is specifically designed for patients with cognitive impairment due to schizophrenia. The trial aims to assess the long-term safety of Iclepertin in participants who have completed previous Phase III trials.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of Iclepertin to evaluate its safety profile over an extended period. Participants' compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial is structured as an open-label, single-arm extension study, allowing for the collection of additional safety data in the specified patient population.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint focuses on the occurrence of treatment emergent adverse events (TEAEs) throughout the extension study. Secondary endpoints include the change from baseline in Clinical Global Impressions – Severity (CGI-S) to the end of treatment (EOT) and the change from baseline in hemoglobin (Hb) levels to EOT. These parameters will be measured and collected at specified timepoints, ensuring a comprehensive evaluation of the treatment's impact on patients with schizophrenia. The CGI-S is a validated scale used to assess the severity of a patient's condition, providing a standardized method for evaluating changes in clinical status. The trial is designed to collect additional safety data in patients with cognitive impairment due to schizophrenia, who have completed a previous 26-week treatment period with **Iclepertin** or a matching placebo in one of the phase III clinical trials. The data collection and analysis will adhere to rigorous clinical trial standards to ensure the reliability and validity of the findings.