Long-Term Safety Study for Cushing's Syndrome

(ISS-CA-2023 Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess the long-term safety of osilodrostat for individuals with Cushing's syndrome, a condition characterized by excessive cortisol production. It specifically targets those already using osilodrostat and who found it beneficial in a previous study. The trial will maintain the same medication dosage as before. Suitable candidates are those already benefiting from osilodrostat treatment in a prior study. As a Phase 4 trial, this research seeks to understand how the FDA-approved treatment benefits a broader patient population.

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 is the safety track record for osilodrostat?

Research has shown that osilodrostat is generally safe for people with Cushing's syndrome. In studies involving over 200 patients, those taking osilodrostat maintained good control of their cortisol levels, crucial for managing the condition. Most patients used osilodrostat for several years without major issues.

Some common side effects included tiredness, nausea, and headache. Despite these, many patients continued using the medication due to its effectiveness in managing their condition. Overall, this treatment has proven safe for long-term use in controlling symptoms of Cushing's syndrome. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Osilodrostat is unique because it specifically inhibits an enzyme called 11β-hydroxylase, which plays a crucial role in cortisol production. Unlike traditional treatments for Cushing's Syndrome, such as surgery or other medications that may not directly target cortisol production, osilodrostat offers a more direct approach to control cortisol levels. Researchers are excited about osilodrostat because it has the potential to effectively manage cortisol levels with precise targeting, offering a promising alternative for patients who might not respond well to existing therapies.

What is the effectiveness track record for osilodrostat in treating Cushing's Syndrome?

Research has shown that osilodrostat effectively lowers cortisol levels in people with Cushing's syndrome. In studies, patients quickly and consistently experienced reduced cortisol levels, a hormone often elevated in Cushing's syndrome. This treatment also helped with related health issues, such as high blood pressure. Over time, patients noticed improvements in their physical health and experienced fewer symptoms. Osilodrostat has proven effective for treating Cushing's syndrome, which is why researchers are using it in this long-term safety study. ^{3 5 6 7 8}

Who Is on the Research Team?

André Lacroix, MD

Principal Investigator

Centre hospitalier de l'Université de Montréal (CHUM)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

RECORDATI GROUP

Industry Sponsor

Trials

13

Recruited

4,500+

Published Research Related to This Trial

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40226519/

Osilodrostat Treatment of Cushing Syndrome in Real- ... In clinical trials, osilodrostat (11β-hydroxylase inhibitor) effectively reduced cortisol levels in patients with endogenous Cushing syndrome (CS).

2. academic.oup.com academic.oup.com/ejendo/advance-article/doi/10.1093/ejendo/lvaf207/8276112

Osilodrostat dose impact on efficacy/safety in Cushing's disease Osilodrostat provided rapid reductions in 24-h mean urinary free cortisol (mUFC) levels, which were maintained for long periods.8,11-15 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02697734

Efficacy and Safety Evaluation of Osilodrostat in Cushing's ... The purpose of this study was to confirm efficacy and safety of osilodrostat for the treatment of patients with Cushing's disease who are candidates for medical ...

4. mdpi.com mdpi.com/2077-0383/14/21/7575

Real-World Data on the Efficacy and Safety of Osilodrostat ... Significant improvement in comorbidities was observed after initiation of osilodrostat, with reductions in both SBP and DBP, along with a decrease in the number ...

5. frontiersin.org frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1236465/full

Long-term efficacy and safety of osilodrostat in patients ... Osilodrostat provided long-term control of cortisol secretion that was associated with sustained improvements in clinical signs and physical manifestations of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12545898/

SUN-054 Long-Term, Real-World, Safety and Effectiveness ... Here, we report AEs in the safety population (≥1 osilodrostat dose; n=206) among pts with Cushing's disease (CD) and non-pituitary CS (non-PCS, ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36219274/

Long-term efficacy and safety of osilodrostat in Cushing's ... In the longest prospective study of a steroidogenesis inhibitor to date, osilodrostat provided sustained reductions in mUFC for up to 6.7 years of treatment ...

8. endocrine-abstracts.org endocrine-abstracts.org/ea/0099/ea0099p521

Assessing long-term safety and efficacy of osilodrostat in ... Osilodrostat is generally well-tolerated in endogenous CS patients and provides control of cortisol production in most prior and new osilodrostat users.