Cushing Disease, Cushing Syndrome, Ectopic ACTH Syndrome
Conditions
Keywords
Cushing Syndrome, Cushing Disease, Ectopic ACTH Syndrome, CRN04894, atumelnant
Brief summary
A Phase 1b/2a, first-in-disease, open-label, multiple-ascending dose exploratory study to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamic biomarker responses associated with CRN04894 (an adrenocorticotropic hormone \[ACTH\] receptor antagonist) in participants with ACTH-dependent Cushing's syndrome (Cushing's disease or Ectopic ACTH Syndrome \[EAS\])
Detailed description
This is a Phase 1b/2a, first-in-disease, open-label, multiple-ascending dose exploratory study to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamic biomarker responses associated with atumelnant (also known as CRN04894) (an adrenocorticotropic hormone \[ACTH\] receptor antagonist) over a 10-day or 14-day treatment period in participants with ACTH-dependent Cushing's syndrome (Cushing's disease or Ectopic ACTH Syndrome \[EAS\]). Participants will receive oral atumelnant once daily for 10 days followed by monitoring during 4 'wash-out' days, or for 14 days.
Interventions
DRUGatumelnant
Atumelnant is an orally active investigational agent which antagonizes the action of ACTH at its receptor administered as oral tablets.
Sponsors
Crinetics Pharmaceuticals Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult male or female, aged 18 years or more 2. Evidence of chronic 'active' ACTH-dependent Cushing's syndrome 3. Evidence of acutely 'active' ACTH-dependent Cushing's syndrome within 10 days of Day 1 4. Participants with documented ACTH-dependent Cushing's syndrome taking short-acting steroidogenesis inhibitors (ketoconazole, levoketoconazole, osilodrostat, or metyrapone) may participate after a washout period of at least 5 days, if they meet other study inclusion criteria, relative to Investigator's judgment. Participants with documented ACTH-dependent Cushing's syndrome taking cabergoline may participate after a washout period of at least 14 days, if they meet other study inclusion criteria
Exclusion criteria
1. Women who are pregnant or lactating 2. History of bilateral adrenalectomy 3. Previous pituitary MRI findings of a putative ACTH-secreting lesion within 3 mm of the optic chiasm 4. Presence of any known malignancy 5. Use of mitotane 6. Previous unsuccessful surgery for Cushing's syndrome within 6 weeks
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of participants with treatment emergent adverse events (TEAEs) | Up to Day 15 |
| Proportion of participants with adrenal insufficiency | Up to Day 15 |
| Proportion of participants with safety findings determined by laboratory testing | Up to Day 15 |
| Assessment of the maximum observed plasma concentration of CRN04894 | Up to Day 15 |
| Assessment of the time to achieve maximum observed plasma concentration of CRN04894 | Up to Day 15 |
| Assessment of the plasma area under the curve of CRN04894 | Up to Day 15 |
Secondary
| Measure | Time frame |
|---|---|
| Change from baseline in early morning serum cortisol | Up to Day 15 |
Countries
United States
Outcome results
None listed