Clinical trial NCT02804750: Study to Evaluate CORT125134 in Participants With Cushing's Syndrome
Official title: Phase 2 Study of the Safety and Efficacy of CORT125134 in the Treatment of Endogenous Cushing's Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cushing's Syndrome
Keywords: 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
Lead sponsor: Corcept Therapeutics
Sponsor class: INDUSTRY
First posted: 2016-06-17
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With One or More Adverse Events
timeFrame: Group 1: up to Week 16; Group 2: up to Week 20
measure: Percentage of Participants With One or More Severe (≥Grade 3) Adverse Events
timeFrame: Group 1: up to Week 16; Group 2: up to Week 20
Secondary outcomes:
measure: Percentage of Participants With Hypertension Who Experience Improvement in Blood Pressure Following Treatment With CORT125134
timeFrame: Group 1: Week 12 or last observation; Group 2: Week 16 or last observation
measure: Percentage of Participants With IGT / T2DM Who Experienced a ≥25% Reduction in AUCglucose Following Treatment With CORT125134
timeFrame: 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)
Other outcomes:
Locations:
city: Laguna Hills
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Fort Lauderdale
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Indianapolis
country: United States
state: Indiana
city: Covington
country: United States
state: Kentucky
city: Rochester
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: New York
country: United States
state: New York
city: Cleveland
country: United States
state: Ohio
city: Pittsburgh
country: United States
state: Pennsylvania
city: Richmond
country: United States
state: Virginia
city: Budapest
country: Hungary
city: Pecs
country: Hungary
city: Cuneo
country: Italy
city: Messina
country: Italy
city: Milano
country: Italy
city: Naples
country: Italy
city: Orbassano
country: Italy
city: Roma
country: Italy
city: Siena
country: Italy
city: Torino
country: Italy
city: Leiden
country: Netherlands
city: Rotterdam
country: Netherlands
city: Salford
country: United Kingdom
state: Manchester
Study officials:
affiliation: Corcept Therapeutics
name: Andreas G Moraitis, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.