Long-Term Safety Study for Cushing's Syndrome

(ISS-CA-2023 Trial)

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Must be taking: Osilodrostat

Disqualifiers: New patients, Pregnant, Nursing, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

Duration: up to 2 years

7 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the study is for patients already on osilodrostat, you will likely need to continue with this medication.

What data supports the effectiveness of the drug Osilodrostat for treating Cushing's syndrome?

Research shows that Osilodrostat is effective in controlling Cushing's disease, a condition related to Cushing's syndrome, by reducing cortisol levels in the body. Studies like the LINC 3 and LINC 4 have demonstrated its long-term efficacy and safety in patients with Cushing's disease. ^{1 2 3 4 5}

What safety information is available for Osilodrostat in humans?

Osilodrostat has been studied for long-term safety in patients with Cushing's disease, showing it can be generally safe but may cause some side effects like increased hormone levels and adrenal gland issues after stopping the drug. It is important to monitor patients closely during and after treatment. ^{2 3 4 5 6}

How is the drug osilodrostat different from other treatments for Cushing's syndrome?

Osilodrostat is unique because it is an oral medication that inhibits cortisol production by blocking an enzyme called 11β-hydroxylase, which is different from other treatments that may involve surgery or different mechanisms. It is particularly useful for patients who cannot undergo surgery or have residual disease after surgery. ^{2 3 4 5 7}

What is the purpose of this trial?

The purpose of this study is to continue the evaluation of long-term safety of osilodrostat in 7 Canadian patients who have already received osilodrostat treatment in a previous Global Recordati-sponsored roll-over study and who, based on investigators' judgement, will continue benefiting with its administration.

Research Team

André Lacroix, MD

Principal Investigator

Centre hospitalier de l'Université de Montréal (CHUM)

Eligibility Criteria

This trial is for Canadian patients with Cushing's Syndrome who have shown good adherence to a previous osilodrostat treatment study, are willing to follow the new study plan, and continue to benefit from osilodrostat as judged by their doctor. It excludes new patients, those discontinued from prior osilodrostat studies, or women who are pregnant or nursing.

Inclusion Criteria

You are already taking osilodrostat as part of another study sponsored by Global Recordati for a condition called endogenous CS and have completed all the requirements for that study.

I am willing and able to follow the study's schedule and treatment plan.

Patient has demonstrated compliance, as assessed by the Investigator, with the parent roll-over study protocol requirements.

Exclusion Criteria

Patient has been permanently discontinued from osilodrostat study treatment in the parent roll-over Recordati-sponsored study.

Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory evaluation.

New patients not previously enrolled in parent roll-over Recordatisponsored study.

Timeline

Treatment

Participants continue treatment with osilodrostat as soon as they are enrolled, with quarterly visits for safety and clinical benefit assessments

up to 2 years

Quarterly visits (every 12 weeks ± 2 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

Open-label extension

Participants continue treatment until they are no longer benefiting, osilodrostat becomes commercially available, or other discontinuation criteria are met

Long-term

Treatment Details

Interventions

• Osilodrostat

Trial Overview The trial aims to assess the long-term safety of continued use of osilodrostat in seven Canadian patients with endogenous Cushing's Syndrome. These individuals have previously participated in another related study and will keep receiving this medication under investigator supervision.

Participant Groups

Group I: Participant Group/Arm Experimental Treatment 1 Intervention

Other: osilodrostat open label, with patients receiving same dose as provided in the parent study

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Recordati Rare Diseases

Industry Sponsor

Trials

14

Recruited

540+

Findings from Research

In a 48-week Phase III clinical trial involving 60 patients with Cushing's disease, osilodrostat demonstrated long-term efficacy, with 72.4% of patients achieving normalized urinary free cortisol levels by the end of the trial.

Osilodrostat was well tolerated and maintained improvements in clinical signs and physical manifestations of hypercortisolism, indicating it is a safe and effective long-term treatment option for Cushing's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of osilodrostat in patients with Cushing's disease: results from the LINC 4 study extension. Gadelha, M., Snyder, PJ., Witek, P., et al.[2023]

Osilodrostat is an effective treatment for Cushing's disease, significantly reducing 24-hour mean urinary free cortisol levels in 86% of participants in a pivotal phase 3 study, compared to 29% in the placebo group.

While osilodrostat is generally safe, it requires careful monitoring for potential side effects like QT interval prolongation and increased cortisol precursors, which can lead to complications such as hypokalemia and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osilodrostat: A Novel Steroidogenesis Inhibitor to Treat Cushing's Disease. Dougherty, JA., Desai, DS., Herrera, JB.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of osilodrostat in patients with Cushing's disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Prolonged adrenocortical blockade following discontinuation of Osilodrostat. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of osilodrostat in patients with Cushing's disease: results from the LINC 4 study extension. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Long-term outcomes of osilodrostat in Cushing's disease: LINC 3 study extension. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Osilodrostat in Cushing's disease: the management of its efficacy and the pitfalls of post-surgical results. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Osilodrostat: A Novel Steroidogenesis Inhibitor to Treat Cushing's Disease. [2021]

7. Japan pubmed.ncbi.nlm.nih.gov

A multicenter, phase 2 study to evaluate the efficacy and safety of osilodrostat, a new 11β-hydroxylase inhibitor, in Japanese patients with endogenous Cushing's syndrome other than Cushing's disease. [2021]