Study to Evaluate CORT125134 in Participants With Cushing's Syndrome

Study Overview
=================
Brief Summary
-----------------
Cushing's syndrome is a relatively rare disorder caused by prolonged exposure to high levels of the glucocorticoid hormone cortisol. Cushing's syndrome may result from elevated endogenous or exogenous sources of cortisol. Endogenous Cushing's syndrome resulting from cortisol overproduction by the adrenal glands is the subject of this protocol. Patients with exogenous Cushing's syndrome, which develops as a side effect of chronic administration of high doses of glucocorticoids, were not eligible for enrollment in this study. The purpose of this study was to evaluate the safety and efficacy of CORT125134 for treatment of endogenous Cushing's syndrome. The multicenter study was conducted in the United States and in Europe.

Detailed Description
-----------------
This was a Phase 2, open-label study with two dose groups, each with a two-step dose escalation, designed to evaluate the safety and efficacy of CORT125134 for the treatment of endogenous Cushing's syndrome. CORT125134 was administered orally once daily for 16 weeks with dose escalations occurring every 4 weeks. Pharmacokinetics (PK) profiles were generated at every dose level. A data review committee reviewed PK and safety data and recommended the final plan for dose escalation in Group 2.

Official Title
-----------------
Phase 2 Study of the Safety and Efficacy of CORT125134 in the Treatment of Endogenous Cushing's Syndrome

Conditions
-----------------
Cushing's Syndrome

Intervention / Treatment
-----------------
* Drug: CORT125134


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Has a confirmed diagnosis of endogenous Cushing's syndrome. Requires medical treatment of hypercortisolemia. Meets at least one of the following criteria: Has type 2 diabetes mellitus. Has impaired glucose tolerance. Has hypertension. Exclusion Criteria: Has non-endogenous source of hypercortisolemia Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism Has poorly controlled hypertension Has Stage ≥ 4 renal failure

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Low-dose Group<br>100 mg/day for 4 weeks in Period 1, then 150 mg/day for 4 weeks in Period 2, then 200 mg/day for 4 weeks in Period 3. There was no washout between treatment periods. Period 3 was followed by a 4-week follow-up period. Per-protocol, Group 1 did not participate in treatment Period 4. | Drug: CORT125134<br> <br> |
| Experimental: Group 2: High-dose Group<br>250 mg/day for 4 weeks in Period 1, then 300 mg/day for 4 weeks in Period 2, then 350 mg/day for 4 weeks in Period 3, then 400 mg/day for 4 weeks in Period 4. There was no washout between treatment periods. Period 4 was followed by a 4-week follow-up period. | Drug: CORT125134<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With One or More Adverse Events | All treatment-emergent adverse events were recorded and summarized. | Group 1: up to Week 16; Group 2: up to Week 20 | 
| Percentage of Participants With One or More Severe (≥Grade 3) Adverse Events | All treatment-emergent adverse events with Common Terminology Criteria for Adverse Events (CTCAE) ≥Grade 3 (severe) were recorded and summarized. | Group 1: up to Week 16; Group 2: up to Week 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Hypertension Who Experience Improvement in Blood Pressure Following Treatment With CORT125134 | Improvement in blood pressure was defined as a participant who experiences at least a 5 mmHg decrease in mean diastolic or systolic BP from baseline who has not taken an additional antihypertensive medication during the treatment period or increased the dosage of a concurrent antihypertensive medication. | Group 1: Week 12 or last observation; Group 2: Week 16 or last observation | 
| Percentage of Participants With IGT / T2DM Who Experienced a ≥25% Reduction in AUCglucose Following Treatment With CORT125134 | Improvement in glucose control was defined as a participant who experiences at least a 25% decrease from baseline in area under the concentration-time curve for blood glucose (AUCglucose) who has not taken an additional diabetes medication during the treatment period or increased the dosage of a concurrent diabetes medication. | Before and 0.5, 1, 1.5, and 2 hours after a glucose drink at Week 12 or last observation (Group 1) or Week 16 or last observation (Group 2) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cushing's Syndrome, Cushing's Disease, Cushing's, Hypercortisolemia, Cushingoid, Type 2 Diabetes, Impaired Glucose Intolerance, Hypertension, Adrenal Corticotrophic Hormone (ACTH), Adrenocortical Carcinoma, Primary Pigmented Nodular Adrenal Disease (PPNAD), Moon Facies, Dorsocervical Fat Pad, Adrenal Adenoma, Adrenal Carcinoma, Adrenal Autonomy, Cortisol