GRADIENT: Efficacy and Safety of Relacorilant in Patients With Cortisol-Secreting Adrenal Adenomas

• Sponsor: Corcept Therapeutics (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04308590
• Collaborator: (none)
• Enrollment: 130
• Locations: 51
• Arms: 2
• Anticipated Duration (Months): 26.4
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a Phase 3, randomized, double-blind, placebo-controlled study to assess the efficacy, and safety of relacorilant to treat hypercortisolism in patients with cortisol-secreting adrenal adenoma or hyperplasia associated with diabetes mellitus/ impaired glucose tolerance and/or uncontrolled systolic hypertension.

Condition or Disease	Intervention/Treatment	Phase
Hypercortisolism	Drug: relacorilant; Other: Placebo	Phase 3

Detailed Description

This Phase 3 study patients will be randomized in a 1:1 ratio to treatment with relacorilant (active drug) or placebo. Patients will receive relacorilant or placebo for 22 weeks. Patients who complete the study may also be eligible to roll over into an extension study.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 130 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Glucocorticoid Receptor Antagonism in the Treatment of Hypercortisolism in Patients With Cortisol-Secreting Adrenal Adenomas or Hyperplasia: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Relacorilant
• Actual Study Start Date: May 19, 2020
• Anticipated Primary Completion Date: Jul 1, 2022
• Anticipated Study Completion Date: Aug 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Relacorilant The dose of relacorilant will be increased sequentially from 100 mg orally once daily to a target dose of 400 mg once daily.	Drug: relacorilant; Relacorilant is supplied as 100 mg capsules for oral dosing.
Placebo Comparator: Placebo Placebo matched to study drug	Other: Placebo; Placebo is supplied as 100 mg capsules for oral dosing.

Outcome Measures

Primary Outcome Measures

1. In patients with diabetes/ impaired glucose tolerance (DM/IGT), the mean change in AUC glucose as compared between relacorilant and placebo arm [Baseline to week 22]

2. In patients with systolic hypertension, the change in mean systolic blood pressure (SBP) based on 24-hour ambulatory blood pressure monitor (ABPM) as compared between relacorilant and placebo arms [Baseline to week 22]

3. Rate of safety based TEAEs [Baseline to week 22]

   Assessment of safety based on treatment-emergent adverse events (TEAEs) as graded by CTCAE v5.0.

Secondary Outcome Measures

1. In patients with DM at baseline the mean change in HbA1c and fasting glucose [Baseline to week 22/ET]

2. Proportion of patients with IGT at Baseline who achieved normalization of 2-hour oGTT glucose [Week 22/ET]

3. Proportion of patients with normalization of the mean SBP [Baseline to week 22/ET]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Shows lack of cortisol suppression

• Suppressed or low early-morning ACTH levels

• A radiologically confirmed adrenal lesion

• Has IGT or DM

• Has uncontrolled hypertension

Exclusion Criteria:

• Has severe, uncontrolled hypertension

• Has poorly controlled DM

• Has DM Type 1

• Has significantly abnormal liver test results or severe renal insufficiency

• Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 27	Birmingham	Alabama	United States	35294
2	Site 17	Stanford	California	United States	94305
3	Site 07	Atlanta	Georgia	United States	30318
4	Site 16	Indianapolis	Indiana	United States	46202
5	Site 09	Metairie	Louisiana	United States	70006
6	Site 36	Baltimore	Maryland	United States	21287
7	Site 11	Fall River	Massachusetts	United States	02721
8	Site 45	Ann Arbor	Michigan	United States	48109
9	Site 33	Rochester	Minnesota	United States	55905
10	Site 06	Jackson	Mississippi	United States	39202
11	Site 19	Albany	New York	United States	12206
12	Site 10	Jamaica	New York	United States	11432
13	Site 44	New York	New York	United States	10021
14	Site 01	Wilmington	North Carolina	United States	28401
15	Site 30	Cleveland	Ohio	United States	44195
16	Site 21	Columbus	Ohio	United States	43201-3209
17	Site 39	Philadelphia	Pennsylvania	United States	19107
18	Site 12	Pittsburgh	Pennsylvania	United States	15202
19	Site 02	Summerville	South Carolina	United States	29485
20	Site 20	Dallas	Texas	United States	75390
21	Site 03	El Paso	Texas	United States	79935
22	Site 05	Fort Worth	Texas	United States	76132
23	Site 08	Houston	Texas	United States	77079
24	Site 04	Shavano Park	Texas	United States	78231
25	Site 15	Spokane	Washington	United States	99202
26	Site 49	Graz	Styria	Austria	8036
27	Site 25	Wien	Vienna	Austria	1090
28	Site 22	Sofia		Bulgaria	01431
29	Site 50	Munich	Bavaria	Germany	80336
30	Site 46	Wuerzburg		Germany	97080
31	Site 24	Kfar-Saba		Israel	44281
32	Site 18	Petach Tikva		Israel	4941480
33	Site 32	Ramat Gan		Israel	5265601
34	Site 23	Tel Aviv		Israel
35	Site 40	Milan	Milano	Italy	20122
36	Site 31	Rome	Roma	Italy	00189
37	Site 43	Orbassano	Torino	Italy
38	Site 34	Milan		Italy
39	Site 28	Napoli		Italy	80131
40	Site 51	Padova		Italy	35128
41	Site 37	Rome		Italy	00161
42	Site 48	Gliwice		Poland	44-102
43	Site 47	Krakow		Poland	31-501
44	Site 35	Lublin		Poland
45	Site 42	Bucharest		Romania	010825
46	Site 38	Bucharest		Romania	011863
47	Site 41	Bucharest		Romania	011863
48	Site 29	Girona		Spain	17007
49	Site 14	Malaga		Spain	29006
50	Site 13	Sevilla		Spain	41013
51	Site 26	Valencia		Spain	46026

Sponsors and Collaborators

• Corcept Therapeutics

Investigators

• Study Director: Andreas Moraitis, MD, Corcept Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Corcept Therapeutics
• ClinicalTrials.gov Identifier: NCT04308590
• Other Study ID Numbers: CORT125134-456
• First Posted: Mar 16, 2020
• Last Update Posted: Jun 13, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Corcept Therapeutics: Cushing syndrome; Cushing; Hypercortisolemia; Type 2 Diabetes; Impaired Glucose Intolerance; Hypertension; Adrenocorticotropic hormone; Primary Pigmented Nodular Adrenal Disease; Macronodular adrenal hyperplasia; Adrenal Adenoma; Adrenal Autonomy; Cortisol; Autonomous cortisol secretion
• Additional relevant MeSH terms: Adenoma; Adrenocortical Adenoma; Cushing Syndrome; Adrenocortical Hyperfunction

Study Results

No Results Posted as of Jun 13, 2022