Efficacy and Safety Evaluation of Cariprazine in Adolescents with Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study

The primary objective of this study is to evaluate the **efficacy** of cariprazine at doses of 1.5 mg/day and 4.5 mg/day compared to placebo in the treatment of adolescents aged 13 to 17 years with schizophrenia. This is clinically relevant as it aims to determine the therapeutic potential of cariprazine in managing symptoms of schizophrenia in this specific age group, which can significantly impact their quality of life and long-term prognosis.

Secondary objectives include:

• Evaluating the **safety** and tolerability of cariprazine at the specified doses compared to placebo in the same adolescent population. This is crucial for understanding the risk-benefit profile of cariprazine in treating schizophrenia in adolescents, ensuring that the treatment is not only effective but also safe for long-term use.

The clinical trial involved a total of **215 participants**, specifically targeting **adolescent patients** aged 13 to 17 years diagnosed with **schizophrenia**. The study population included both male and female subjects, encompassing a vulnerable population due to the age group and medical condition. Participants were selected based on specific inclusion criteria, such as being inpatients or outpatients within the specified age range, having a DSM-5 primary diagnosis of schizophrenia, and meeting certain scores on the PANSS and CGI-S scales. The trial did not specify any particular lifestyle considerations such as diet or physical activity. The selection process ensured that the participants had a confirmed diagnosis of schizophrenia, as verified by the K-SADS-PL administered by a trained clinician. The sponsor did not provide additional information regarding the general health status or lifestyle habits of the participants.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of **cariprazine** in treating adolescent participants aged 13 to 17 years with **schizophrenia**. The trial will span a duration of six weeks, during which participants will be randomly assigned to receive either cariprazine at doses of 1.5 mg/day or 4.5 mg/day, or a placebo. The primary objective is to assess the change from baseline to Week 6 on the Positive and Negative Syndrome Scale (PANSS) total score, which serves as the primary efficacy endpoint. Secondary endpoints include the comparison of adverse events, clinical laboratory measures, vital signs, and other assessments between cariprazine and placebo groups.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit where eligibility is confirmed based on criteria such as a DSM-5 primary diagnosis of schizophrenia and a PANSS score of ≥ 70. This is followed by a baseline visit where initial assessments are conducted. Throughout the trial, follow-up visits will be scheduled to monitor the participants' response to treatment and any adverse effects. The end-of-study visit will occur at the conclusion of the six-week treatment period, where final assessments will be made to evaluate the overall efficacy and safety of the treatment.

The expected length of participant involvement is six weeks, aligning with the trial's treatment duration. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial aims to provide valuable insights into the treatment of schizophrenia in adolescents, contributing to the understanding of cariprazine's therapeutic potential in this population.

The clinical trial involves the administration of several **experimental medications** and a placebo to evaluate the efficacy and safety of **cariprazine** in adolescents with **schizophrenia**. The first experimental medication is Cariprazine 0.5 mg capsules, hard, containing the active substance **cariprazine hydrochloride**. This medication is manufactured by Gedeon Richter PLC and is presented in a hard capsule form. The route of administration is oral, with a maximum daily dose of 1.5 mg and a total maximum dose of 60 mg over a treatment period of 6 weeks. The pharmaceutical form is a hard capsule, and the medication is not a pediatric formulation.

Another experimental medication used in the trial is Reagila 3 mg hard capsules, which also contains the active substance **cariprazine**. This product is similarly manufactured by Gedeon Richter PLC and is administered orally. The maximum daily dose for this formulation is 4.5 mg, with a total maximum dose of 160.5 mg over the 6-week treatment period. The pharmaceutical form remains a hard capsule, and it is not specifically formulated for pediatric use.

Reagila 4.5 mg hard capsules are also included in the study, containing the same active substance, **cariprazine**. Manufactured by Gedeon Richter PLC, these capsules are administered orally with a maximum daily dose of 4.5 mg and a total maximum dose of 160.5 mg over the 6-week period. The pharmaceutical form is a hard capsule, and it is not a pediatric formulation.

Additionally, Reagila 1.5 mg hard capsules are utilized, containing **cariprazine** as the active substance. These capsules are produced by Gedeon Richter PLC and are administered orally. The maximum daily dose is 1.5 mg, with a total maximum dose of 60 mg over the 6-week treatment period. The pharmaceutical form is a hard capsule, and it is not a pediatric formulation.

For the purpose of the clinical study, a **placebo** formulation was prepared using the same white hard gelatin capsule shell. This placebo is used as a comparator treatment in the study to evaluate the efficacy of the experimental medications. The placebo does not contain any active substance and is designed to match the appearance of the active medication capsules to maintain the double-blind nature of the trial.

The efficacy of cariprazine in the treatment of adolescents with **schizophrenia** will be assessed in a 6-week, international, multicenter, randomized, double-blind, parallel-group, placebo-controlled clinical trial. The primary efficacy endpoint is the change from baseline to Week 6 on the Positive and Negative Syndrome Scale (PANSS) total score. This scale is a validated tool used to measure symptom severity in individuals with schizophrenia. The PANSS will be administered at baseline and at the end of the treatment period to evaluate the efficacy of cariprazine compared to placebo.

Secondary endpoints include the comparison of adverse events (AEs), clinical laboratory measures, vital signs, electrocardiograms (ECG), Columbia-Suicide Severity Rating Scale (C-SSRS), Calgary Depression Scale for Schizophrenia (CDSS), Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), Simpson-Angus Scale (SAS), UKU Side Effect Rating Scale, menstrual cycle assessment, physical examination, and Tanner staging between participants exposed to cariprazine and those receiving placebo. These assessments will provide a comprehensive evaluation of the safety and tolerability of cariprazine in the study population.