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Osilodrostat

Osilodrostat is an investigational drug being studied as a potential treatment for Cushing’s syndrome, a rare hormonal disorder caused by excessive cortisol production. Clinical trials are evaluating osilodrostat’s safety and efficacy in reducing cortisol levels and improving symptoms in patients with various forms of Cushing’s syndrome. This article summarizes key findings from recent clinical trials of osilodrostat.

Table of Contents

What is Osilodrostat?

Osilodrostat is a medication used to treat certain hormonal disorders. It is also known by the brand name Isturisa and was previously called LCI699 during its development.[1] Osilodrostat comes in the form of tablets that are taken by mouth.[2]

What Conditions Does Osilodrostat Treat?

Osilodrostat is primarily used to treat Cushing’s syndrome, especially a type called Cushing’s disease. Cushing’s syndrome is a condition where the body produces too much of a hormone called cortisol.[2] Cortisol is normally produced by the adrenal glands and helps regulate many important functions in the body. However, when too much cortisol is produced, it can cause a variety of symptoms and health problems.

Specifically, osilodrostat has been studied for use in:[3][4]

  • Cushing’s disease (caused by a tumor in the pituitary gland)
  • Ectopic Cushing’s syndrome (caused by tumors outside the pituitary gland)
  • Adrenal tumors causing excess cortisol

How Does Osilodrostat Work?

Osilodrostat works by blocking an enzyme called 11β-hydroxylase, which is involved in producing cortisol in the adrenal glands. By inhibiting this enzyme, osilodrostat reduces the amount of cortisol the body makes.[1] This helps bring cortisol levels back to a normal range in people with Cushing’s syndrome.

How Effective is Osilodrostat?

Clinical trials have shown osilodrostat to be effective in treating Cushing’s syndrome:

  • In one study, about 86% of patients had normal cortisol levels after 24 weeks of treatment.[1]
  • Another trial found that 77% of patients maintained normal cortisol levels for 36 weeks while on osilodrostat.[5]
  • Osilodrostat has also been shown to improve many of the symptoms and health problems associated with Cushing’s syndrome, such as high blood pressure, diabetes, and weight gain.[3]

How is Osilodrostat Taken?

Osilodrostat is taken as tablets by mouth, usually twice a day. The dose is typically started low and then gradually increased over time based on cortisol levels and how well the medication is tolerated.[2] Common doses range from 2 mg to 30 mg twice daily, but the exact dose varies for each patient. Regular blood and urine tests are done to monitor cortisol levels and adjust the dose as needed.

What are the Side Effects of Osilodrostat?

Common side effects of osilodrostat may include:[1][5]

  • Nausea
  • Headache
  • Fatigue
  • Adrenal insufficiency (low cortisol levels)
Adrenal insufficiency can occur if cortisol levels drop too low. Symptoms may include weakness, dizziness, nausea, and low blood pressure. It’s important to monitor for these symptoms and contact your doctor if they occur.

Use in Special Populations

Studies have looked at how osilodrostat is processed by the body in people with liver or kidney problems:

  • For patients with mild to moderate liver problems, no dose adjustment is typically needed.[6]
  • For patients with kidney problems, the medication may stay in the body longer, so dose adjustments may be necessary.[7]
Always inform your doctor about any liver or kidney conditions you have before starting osilodrostat.

Ongoing Research on Osilodrostat

Research on osilodrostat is ongoing to learn more about its long-term use and effectiveness in different types of Cushing’s syndrome. Some current studies are:

  • Looking at the long-term safety and effectiveness of osilodrostat in patients with various types of Cushing’s syndrome[2]
  • Studying a treatment approach that combines osilodrostat with steroid replacement therapy[8]
  • Evaluating osilodrostat in patients with Cushing’s syndrome not caused by Cushing’s disease[4]
These ongoing studies will help doctors better understand how to use osilodrostat and who might benefit most from this treatment.

Aspect Details
Study Designs Phase II and III trials, including open-label, randomized withdrawal, and long-term extension studies
Patient Populations Adults with various forms of Cushing’s syndrome, including Cushing’s disease and ectopic Cushing’s syndrome
Primary Endpoints Normalization of urinary free cortisol (UFC) levels, typically defined as mUFC ≤ upper limit of normal (ULN)
Secondary Endpoints Changes in clinical signs/symptoms, cardiovascular risk factors, quality of life measures, and long-term safety assessments
Dosing Oral administration, typically starting at low doses (1-2 mg twice daily) with gradual titration based on UFC levels and tolerability
Treatment Duration Initial periods of 24-48 weeks, with some studies including extension phases up to 3 years or more
Safety Monitoring Adverse events, laboratory tests, ECGs, and special assessments for adrenal insufficiency and hormone-related effects
Pharmacokinetics Evaluation of osilodrostat concentrations in plasma, including studies in patients with hepatic and renal impairment

FAQ

  • What is osilodrostat and how does it work? Osilodrostat is an oral medication that inhibits an enzyme involved in cortisol production. It works by blocking the final step of cortisol synthesis in the adrenal glands, helping to reduce excessive cortisol levels in patients with Cushing's syndrome.
  • What types of Cushing's syndrome is osilodrostat being studied for? Clinical trials are evaluating osilodrostat for various forms of Cushing's syndrome, including Cushing's disease (pituitary-dependent Cushing's syndrome), ectopic Cushing's syndrome, and adrenal-dependent Cushing's syndrome.
  • What are the main outcomes being measured in osilodrostat clinical trials? Key outcomes include changes in urinary free cortisol (UFC) levels, clinical signs and symptoms of Cushing's syndrome, quality of life measures, and safety assessments. Many trials are looking at the percentage of patients achieving normal UFC levels with osilodrostat treatment.
  • How long do the clinical trials of osilodrostat typically last? The duration of osilodrostat trials varies, but many include an initial treatment period of 24-48 weeks, followed by longer-term extension periods to assess safety and efficacy for up to several years in some cases.
  • What are some of the potential side effects of osilodrostat being monitored? Common side effects being monitored include nausea, headache, fatigue, and adrenal insufficiency. Trials are also assessing cardiovascular effects, changes in hormone levels, and long-term safety with extended use of osilodrostat.

Ongoing Clinical Trials on Osilodrostat

  • Study of Osilodrostat for Children and Adolescents with Cushing’s Disease

    Not recruiting

    1 1 1
    Investigated drugs:
    Belgium France Italy

Glossary

  • Cushing's syndrome: A hormonal disorder caused by prolonged exposure to high levels of cortisol. It can result from various causes, including pituitary tumors, adrenal tumors, or long-term use of corticosteroid medications.
  • Urinary free cortisol (UFC): A measure of cortisol levels in a 24-hour urine sample. It is commonly used to diagnose and monitor Cushing's syndrome.
  • Mean UFC (mUFC): The average of multiple 24-hour urinary free cortisol measurements, often used as a key endpoint in clinical trials.
  • Upper limit of normal (ULN): The highest value of a physiological measurement that is considered normal. In Cushing's syndrome trials, UFC levels are often compared to the ULN.
  • Adrenal insufficiency: A condition in which the adrenal glands do not produce enough steroid hormones, particularly cortisol. It can occur as a side effect of treatments that lower cortisol levels.
  • Pharmacokinetics (PK): The study of how a drug is absorbed, distributed, metabolized, and eliminated by the body. PK studies help determine appropriate dosing and potential drug interactions.
  • Quality of life (QoL): A measure of an individual's overall well-being and ability to function in daily life. QoL assessments are important in evaluating the impact of Cushing's syndrome and its treatments.
  • Randomized withdrawal: A study design where participants who respond to a treatment are randomly assigned to continue the treatment or switch to placebo, used to evaluate long-term efficacy and potential for relapse.
  • Extension period: An additional phase of a clinical trial that allows participants to continue receiving the study treatment after the main study period ends, often used to gather long-term safety and efficacy data.
  • Dose titration: The process of adjusting the dose of a medication to find the optimal balance between effectiveness and side effects for each individual patient.

References

  1. https://clinicaltrials.gov/study/NCT02180217
  2. https://clinicaltrials.gov/study/NCT05382156
  3. https://clinicaltrials.gov/study/NCT02468193
  4. https://clinicaltrials.gov/study/NCT05633953
  5. https://clinicaltrials.gov/study/NCT02697734
  6. https://clinicaltrials.gov/study/NCT02372084
  7. https://clinicaltrials.gov/study/NCT02399202
  8. https://clinicaltrials.gov/study/NCT06430528