Study to Evaluate CORT125134 in Participants With Cushing's Syndrome

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.

• CORT125134 (Drug)

Primary outcomes

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

Secondary outcomes

• Percentage of Participants With Hypertension Who Experience Improvement in Blood Pressure Following Treatment With CORT125134 [Group 1: Week 12 or last observation; Group 2: Week 16 or last observation]: 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.
• Percentage of Participants With IGT / T2DM Who Experienced a ≥25% Reduction in AUCglucose Following Treatment With CORT125134 [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)]: 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.

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

1. Has a confirmed diagnosis of endogenous Cushing's syndrome.
2. Requires medical treatment of hypercortisolemia.
3. Meets at least one of the following criteria:

   1. Has type 2 diabetes mellitus.
   2. Has impaired glucose tolerance.
   3. Has hypertension.

Exclusion Criteria:

1. Has non-endogenous source of hypercortisolemia
2. Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism
3. Has poorly controlled hypertension
4. Has Stage ≥ 4 renal failure

Participant flow

Outcome results

• Percentage of Participants With One or More Adverse Events (Primary), Count of participants, Participants: Group 1: Low-dose Group 15; Group 2: High-dose Group 18
• Percentage of Participants With One or More Severe (≥Grade 3) Adverse Events (Primary), Count of participants, Participants: Group 1: Low-dose Group 3; Group 2: High-dose Group 7
• Percentage of Participants With Hypertension Who Experience Improvement in Blood Pressure Following Treatment With CORT125134 (Secondary), Number, Percentage of participants: Group 1: Low-dose Group 41.67 (15.17 to 72.33); Group 2: High-dose Group 63.64 (30.79 to 89.07)
• Percentage of Participants With IGT / T2DM Who Experienced a ≥25% Reduction in AUCglucose Following Treatment With CORT125134 (Secondary), Number, Percentage of participants: Group 1: Low-dose Group 23.08 (5.04 to 53.81); Group 2: High-dose Group 0 (0 to 23.16)
• Percentage of Participants With IGT / T2DM Who Experienced Improvement in Glucose Control Following Treatment With CORT125134: Responder Definition Based on Response Criteria for Phase 3 Study NCT03697109 (Post hoc), Number, Percentage of participants: Group 1: Low-dose Group 15.38 (1.92 to 45.45); Group 2: High-dose Group 50.00 (21.09 to 78.91)

Adverse events

Time frame: Group 1: up to Week 16; Group 2: up to Week 20

Serious adverse events by term

Other adverse events by term

52 more terms not shown.

• Results publication: Pivonello R, Munster PN, Terzolo M, Ferrigno R, Simeoli C, Puglisi S, Bali U, Moraitis AG. Glucocorticoid Receptor Antagonism Upregulates Somatostatin Receptor Subtype 2 Expression in ACTH-Producing Neuroendocrine Tumors: New Insight Based on the Selective Glucocorticoid Receptor Modulator Relacorilant. Front Endocrinol (Lausanne). 2022 Jan 4;12:793262. doi: 10.3389/fendo.2021.793262. eCollection 2021. PMID 35058882
• Results publication: Pivonello R, Bancos I, Feelders RA, Kargi AY, Kerr JM, Gordon MB, Mariash CN, Terzolo M, Ellison N, Moraitis AG. Relacorilant, a Selective Glucocorticoid Receptor Modulator, Induces Clinical Improvements in Patients With Cushing Syndrome: Results From A Prospective, Open-Label Phase 2 Study. Front Endocrinol (Lausanne). 2021 Jul 14;12:662865. doi: 10.3389/fendo.2021.662865. eCollection 2021. PMID 34335465

• Study Protocol (PDF, 2018-01-15)
• Statistical Analysis Plan (PDF, 2018-08-30)

• Andreas G Moraitis, MD, Study director, Corcept Therapeutics