Evaluation of Pharmacokinetics, Pharmacodynamics, and Tolerability of Osilodrostat in Pediatric and Adolescent Patients with Cushing's Disease

The primary objective of this phase II, multicenter, open-label, non-comparative study is to evaluate the **pharmacokinetics** (PK) of osilodrostat in children and adolescents aged 6 to less than 18 years with Cushing's disease. Understanding the pharmacokinetics is crucial for determining the appropriate dosing regimen, ensuring therapeutic efficacy, and minimizing potential adverse effects in this pediatric population.

The secondary objectives include the assessment of the pharmacodynamics, safety, and tolerability of osilodrostat. These evaluations are essential to comprehensively understand the drug's action, its safety profile, and its acceptability in the target population, thereby supporting its potential use in clinical practice for managing Cushing's disease in younger patients.

The clinical trial involves a total of **2 participants** diagnosed with **Cushing's disease**. The study population consists of both male and female children and adolescents aged 6 to less than 18 years. Participants are required to have a body weight greater than 30 kg and must be able to swallow study drug tablets whole. The trial population was selected based on the failure of previous surgical interventions, pending surgery, or situations where surgery is not an immediate option. The participants' general health status is characterized by a confirmed diagnosis of Cushing's disease of endogenous origin. The trial includes a vulnerable population, as it involves minors, and requires consent or assent from parents or legal guardians. No specific lifestyle considerations such as diet or physical activity are mentioned for this study.

The clinical trial is a **phase II**, multicenter, open-label, non-comparative study designed to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of **osilodrostat** in children and adolescent patients with **Cushing's disease**. The trial aims to assess the pharmacokinetic parameters of osilodrostat in participants aged 6 to less than 18 years who have either failed surgery, are awaiting surgery, or for whom surgery is not an immediate option. The study will involve the administration of Isturisa film-coated tablets, available in 1 mg, 5 mg, and 10 mg dosages, with a maximum daily dose of 60 mg. The trial is expected to last until November 30, 2025, with participant involvement potentially extending up to 48 weeks.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, body weight, and the ability to swallow tablets. Following the screening, participants will attend regular follow-up visits to monitor pharmacokinetic parameters, safety, and tolerability. The primary endpoint focuses on the pharmacokinetic parameters of osilodrostat, while secondary endpoints include the proportion of patients achieving normal mean urinary free cortisol (mUFC) levels, changes in mUFC from baseline, and overall safety and tolerability.

The trial will conclude with an end-of-study visit, where final assessments will be conducted. Participants may be withdrawn from the study early if they experience adverse effects, fail to comply with the study protocol, or if the investigator deems it necessary for their safety. The study is not categorized as low intervention and is conducted under the authorization of relevant regulatory bodies. The trial's design and procedures ensure a comprehensive evaluation of osilodrostat's effects in the target population, contributing valuable data to the understanding of its use in treating Cushing's disease in pediatric patients.

The clinical trial involves the administration of **Isturisa** film-coated tablets, which contain the active substance **osilodrostat**. Osilodrostat is a chemical compound classified under the ATC code H02CA, indicating its role as an anticorticosteroid. The trial utilizes three different dosages of Isturisa: 1 mg, 5 mg, and 10 mg film-coated tablets. Each tablet is designed for **oral use**. The maximum daily dose for participants is set at 60 mg, with a total treatment period not exceeding 48 weeks. The pharmaceutical form of the medication is consistent across all dosages, ensuring uniformity in administration.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are employed. The focus remains solely on evaluating the pharmacokinetics, pharmacodynamics, and tolerability of osilodrostat in the specified patient population. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial is conducted under the sponsorship of Recordati Rare Diseases, with the medication holding marketing authorization in the European Union.

The efficacy of **osilodrostat** in the clinical trial will be assessed through several key endpoints. The primary endpoint focuses on the pharmacokinetic parameters of osilodrostat in children and adolescents aged 6 to less than 18 years with Cushing's disease. Secondary endpoints include the proportion of patients achieving normal mean urinary free cortisol (mUFC) levels, the absolute values of mUFC, and changes from baseline. Additionally, safety and tolerability will be evaluated as part of the secondary endpoints.

Data collection will involve measuring mUFC levels, which serve as a biomarker for assessing the efficacy of the treatment. The trial is designed as a phase II, multicenter, open-label, non-comparative study, ensuring a comprehensive evaluation of the pharmacokinetics, pharmacodynamics, and tolerability of osilodrostat. The study will include male and female participants who meet specific inclusion criteria, such as a confirmed diagnosis of Cushing's disease and a body weight greater than 30 kg. The trial is expected to conclude by November 30, 2025.