Evaluation of Long-Term Safety and Tolerability of Cariprazine in Adolescent Patients with Schizophrenia: A 2-Year, Multicenter, Open-Label Study

The primary objective of this study is to evaluate the long-term **safety** and **tolerability** of cariprazine, administered at doses ranging from 1.5 mg/day to 6.0 mg/day, in the treatment of adolescents aged 13 to less than 18 years with schizophrenia. This is clinically relevant as it aims to ensure that cariprazine is a safe and well-tolerated treatment option for this specific age group, which is crucial for managing schizophrenia effectively in adolescents.

Secondary objectives include:

• Evaluating the long-term effectiveness of cariprazine in treating adolescents with schizophrenia.
• Assessing health-related outcomes during long-term treatment with cariprazine in this patient population.

The clinical trial involves **adolescent patients** aged 13 to less than 18 years, diagnosed with **schizophrenia**. Both male and female participants are included in the study, and the trial population is considered vulnerable. The sponsor has not provided information regarding the total number of participants. Participants were selected based on specific criteria, including a primary diagnosis of schizophrenia confirmed by the K-SADS-PL, and a PANSS total score of 60 or less at screening and baseline. The study aims to evaluate the long-term safety and tolerability of cariprazine, with dosages ranging from 1.5 mg to 6.0 mg per day. Participants are required to adhere to certain lifestyle considerations, such as agreeing to sexual abstinence or using highly effective contraceptive methods during the study and for 10 weeks after the last dose of the investigational medicinal product. The trial includes both new patients and those who turn 18 during the study, provided they meet the age criteria at screening.

The clinical trial is designed to evaluate the long-term safety and tolerability of **cariprazine** in adolescent patients aged 13 to 17 years with schizophrenia. This is a two-year, multicenter, open-label, flexible-dose study. The trial involves the administration of cariprazine in doses ranging from 1.5 mg to 6.0 mg per day, delivered in hard capsule form for oral use. The study is not categorized as low intervention and is classified as a Phase III trial. The trial is expected to commence recruitment on June 14, 2024, and conclude by November 30, 2024.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of schizophrenia according to DSM-5, and specific scores on the PANSS and CGI-S scales. Following the screening, eligible participants will be enrolled in the study and will attend regular follow-up visits to monitor safety and efficacy outcomes. These visits will include assessments of adverse events, clinical laboratory tests, vital signs, weight, physical examinations, and various psychiatric scales such as the PANSS, CGI-S, and CGI-I. The end-of-study visit will mark the completion of the participant's involvement, which is anticipated to last up to 104 weeks.

Participants are expected to adhere to the study protocol, including the use of effective contraceptive methods and abstaining from sperm donation for a specified period. Conditions that may lead to early termination from the study include non-compliance with the protocol, withdrawal of consent, or the occurrence of significant adverse events. The primary outcome measures focus on safety parameters, while secondary outcomes assess the effectiveness of the treatment and health-related quality of life. The trial aims to provide comprehensive data on the safety profile of cariprazine in the adolescent population with schizophrenia.

The clinical trial involves the administration of several **experimental medications** containing the active substance **cariprazine**. The primary investigational product is Reagila, available in various dosages: 6 mg, 4.5 mg, 3 mg, and 1.5 mg, all formulated as hard capsules. These capsules are intended for **oral use** and are manufactured by Gedeon Richter PLC. The maximum daily dose for each formulation is 6 mg, with a treatment period extending up to 104 weeks. The administration schedule is flexible, allowing for dose adjustments within the specified range to evaluate the long-term safety and tolerability in adolescent patients with **schizophrenia**.

Additionally, the trial includes Cariprazine 0.5 mg capsules, also in hard capsule form, containing the active substance **cariprazine hydrochloride**. This formulation is similarly administered orally, with a maximum daily dose of 6 mg and a treatment duration of up to 104 weeks. The capsules are produced by Gedeon Richter PLC and are part of the flexible dosing regimen designed to assess the safety and tolerability of cariprazine in the target population.

Throughout the study, participant compliance with the dosing schedule will be monitored to ensure adherence to the prescribed regimen. The trial does not include any non-experimental treatments such as placebo or comparator therapies, focusing solely on the evaluation of cariprazine's safety profile in the specified patient group.

The efficacy of **cariprazine** in the treatment of adolescent patients with schizophrenia will be assessed using a range of secondary outcome measures. These include the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions-Severity (CGI-S), Clinical Global Impressions-Improvement (CGI-I), Children's Global Assessment Scale (C-GAS), and the Clinical Decision Rule (CDR) system. Health-related outcomes will be evaluated using the Caregiver Strain Questionnaire (CGSQ) and the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q). These assessments will be conducted at various timepoints throughout the study to monitor changes in symptom severity and overall patient well-being.