Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06430528
Other study ID # HUM00246263
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date May 2024
Est. completion date August 2027

Study information

Verified date May 2024
Source University of Michigan
Contact Eyad Alsafadi
Phone 734-647-5661
Email alsafade@med.umich.edu
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

The major goal of this study is to determine the incidence of adrenal insufficiency in patients with endogenous Cushing syndrome receiving osilodrostat treatment combined with a replacement of glucocorticoid (block-and-replace approach). The investigators are also evaluating new biomarker steroids to reflect adequate osilodrostat dosing, the durability and safety, and clinical improvement during treatment.


Description:

Phase 1 (Titration): Participants will provide written informed consent and receive the first dose of osilodrostat (1-2 mg) in the evening. The following morning, participants will add treatment with at least a physiologic replacement dose of methylprednisolone (4-6 mg/d based on body size in not more than 2 divided doses) and concurrently continue 1-2 mg BID of osilodrostat. Frequent communication is maintained with each participant, at least twice weekly for the first 3 months and weekly thereafter until target osilodrostat dose is reached. Study personnel will ask targeted questions related to the primary endpoint with parameters to notify the study physicians for early signs of adrenal insufficiency. Participants are instructed to double their methylprednisolone dose for intercurrent illness and for symptoms of cortisol deficiency or withdrawal that do not resolve with pausing osilodrostat dosing. Every 4-12 weeks, an AM cortisol, as well as a research sample for steroid profiling (including 11OHA4), is obtained prior to the first doses of methylprednisolone and osilodrostat. The osilodrostat dose is up-titrated as necessary to achieve an AM cortisol goal of <5 µg/dL. Once the AM cortisol is at goal, a late-night saliva cortisol (LNSC) and 24 h urine free cortisol (UFC) is obtained per standard of care. Osilodrostat titration is continued if necessary until the UFC is also at goal of <10 µg/24h. Once the AM cortisol and UFC are at goals (<5 µg/dL and <10 µg/24h, respectively), the primary endpoint measures are completed, and the participant enters Phase 2. Phase 2 (Maintenance): Once the participant reaches what the investigator considers the maintenance doses of osilodrostat and methylprednisolone, participants are followed for a total of 48 weeks from the first osilodrostat dose before being considered at the end of study. The AM serum cortisol, UFC, and LNSC are repeated at the end of the 48-week period and as clinically indicated throughout Phase 2, generally every 3-6 months.


Recruitment information / eligibility

Status Recruiting
Enrollment 12
Est. completion date August 2027
Est. primary completion date May 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility Inclusion Criteria: - Endogenous Cushing syndrome, either following surgery or not candidates for surgery - Under consideration to receive osilodrostat as part of their clinical care - Able to provide informed consent. Exclusion Criteria: - Treatment with other investigational drugs within 30 days or five half-lives (whichever is longer). - A history of hypersensitivity to osilodrostat or therapies of a similar chemical class.

Study Design


Intervention

Drug:
Osilodrostat
Add methylprednisolone to osilodrostat therapy after first dose and continue during osilodrostat titration.

Locations

Country Name City State
United States University of Michigan Ann Arbor Michigan

Sponsors (2)

Lead Sponsor Collaborator
University of Michigan Recordati Rare Diseases

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Percent of participants who experience an adrenal insufficiency event during Phase 1 (titration phase) based on evidence of hypotension (systolic BP <90 mmHg) and/or hypoglycemia (glucose <45 mg/dL) with antecedent symptoms (examples: anorexia, nausea, abdominal pain, orthostasis) and with a resolution of signs upon receiving rescue glucocorticoid therapy Through phase 1, approximately 24 weeks
Secondary Correlation between AM cortisol and 11OHA4 measurements compare biomarkers measured by mass spectrometry. This may be calculated Upon 12 participants completing phase 1 or at the end of the study, whichever comes first. Up to end of study, approximately 48 weeks
Secondary Adrenal insufficiency episodes during Phase 2 (maintenance) based on evidence of hypotension (systolic BP <90 mmHg) and/or hypoglycemia (glucose <45 mg/dL) with antecedent symptoms (examples: anorexia, nausea, abdominal pain, orthostasis) and with a resolution of signs upon receiving rescue glucocorticoid therapy Up to end of phase 2 (approximately 48 weeks)
Secondary Frequency of cortisol withdrawal symptoms Based on patient-reported outcomes Up to end of phase 2 (approximately 48 weeks)
Secondary Change in weight Based on clinic measurements Baseline, end of phase 2 (approximately 48 weeks)
Secondary Change in diastolic blood pressure Based on clinic measurements Baseline, end of phase 2 (approximately 48 weeks)
Secondary Change in systolic blood pressure Based on clinic measurements Baseline, end of phase 2 (approximately 48 weeks)
Secondary Change in HgbA1c Based on clinical laboratory measurements Baseline, end of phase 2 (approximately 48 weeks)
Secondary Change in number of concomitant medications Based on clinic notes, total number of medications used to treat Cushing syndrome comorbidities Baseline, end of phase 2 (approximately 48 weeks)
Secondary Adrenal Insufficiency Assessment Questionnaire scores Custom questionnaire for adrenal insufficiency- 4 Likert questions with scores ranging from 4-20. Higher scores indicate worse symptoms. Up to end of study, approximately 48 weeks
Secondary RAND Short Form (SF)-36 scores The 36-Item Short Form Health Survey (SF-36) is standard RAND form used clinically. It is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 with higher scores indicating a better Health-related Quality of Life. Up to end of study, approximately 48 weeks
Secondary Ease of titration Investigators' judgment (1-5 scale) Up to end of phase 1 (approximately 48 weeks)
See also
  Status Clinical Trial Phase
Enrolling by invitation NCT03282487 - Optimising Steroid Replacement in Patients With Adrenal Insufficiency Phase 4
Not yet recruiting NCT05716607 - Treatment Study in Patients Treated With Both Insulin & Hydrocortisone N/A
Not yet recruiting NCT06435481 - Tolerability and Acceptance of Two Oral Hydrocortisone Compounding Formulation for Pediatrics Phase 4
Recruiting NCT03399383 - Adherence in Chronic Adrenal Insufficiency N/A
Completed NCT01428336 - Value of 25 mcg Cortrosyn Stimulation Test N/A
Completed NCT00851942 - Determination of Method-specific Normal Cortisol and Adrenal Hormone Responses to the Short Synacthen Test Phase 4
Withdrawn NCT00368381 - Hydrocortisone Versus Hydrocortisone Plus Fludrocortisone for the Treatment of Adrenal Insufficiency in Severe Sepsis Phase 4
Active, not recruiting NCT04519580 - Improved Diagnostics and Monitoring of Polymyalgia Rheumatica
Recruiting NCT06008184 - Real-time Monitoring of Cortisol - Comparison of Cortisol Levels in Four Biological Fluids
Completed NCT03013166 - THIN Database Study: Resource Use and Outcomes in Patients With Adrenal Insufficiency Prescribed Hydrocortisone: Immediate, or Modified Release, or Prednisolone
Enrolling by invitation NCT02282150 - Modified-release Compared to Conventional Hydrocortisone on Diurnal Fatigue in Secondary Hypoadrenalism Phase 4
Completed NCT02934399 - Dynamic Hormone Diagnostics in Endocrine Disease
Completed NCT03000231 - Circadian Function and Cardio-metabolic Risk in Adrenal Insufficiency
Completed NCT01960530 - An Investigational Study of Hydrocortisone Phase 1
Completed NCT00552487 - Isolated ACTH Deficiency in Patients With Hashimoto Thyroiditis N/A
Completed NCT00575341 - Dehydroepiandrosterone Substitution in Adolescent and Young Women With Central Adrenal Insufficiency Phase 3
Completed NCT00471900 - Six Months DHEA Treatment in Female Adrenal Failure N/A
Completed NCT03294876 - Rheumatoid Arthritis Adrenal Recovery Study
Completed NCT03709381 - Effect of Adrenocorticotropic Hormone on Vascular Endothelial Growth Factor Release in Children Study Early Phase 1
Recruiting NCT05639127 - The Treatment of Adrenal Crisis With Inhaled Prednisolone Early Phase 1