Cushing SyndromePhase 3GRACENCT03697109
A Study of the Efficacy and Safety of Relacorilant in Patients With Endogenous Cushing Syndrome
A Phase 3 study testing Relacorilant in people with Cushing Syndrome, run by Corcept Therapeutics at 64 sites in 11 countries.
Trial summary
This is a Phase 3, double-blind, placebo-controlled, randomized-withdrawal study to assess the efficacy, safety and pharmacokinetics (PK) of relacorilant in patients with endogenous Cushing syndrome and concurrent type 2 diabetes mellitus/impaired glucose tolerance (DM/IGT) and/or uncontrolled hypertension (HTN). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cushing Syndrome
- What is being tested?
- Relacorilant
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 152 participants
- Where
- 64 sitesin 11 countries
- Study dates
- 15 Nov 2018to 15 Apr 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has a confirmed diagnosis of endogenous Cushing syndrome
- Meets at least 1 of the following criteria:
- Has Type 2 diabetes mellitus
- Has impaired glucose tolerance
- Has hypertension.
Who cannot join
- Has non-endogenous source of hypercortisolism
- Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism
- Has poorly controlled hypertension
- Has poorly controlled diabetes mellitus
- Has severe renal insufficiency.
Trial locations and contacts
64 sites in 11 countries.
64 sites in 11 countries
United States32 sites
Site 8
Albany, New York, 12203
Site 20
Ann Arbor, Michigan, 48109
Site 14
Atlanta, Georgia, 30318
Site 45
Baltimore, Maryland, 21205
Site 46
Boston, Massachusetts, 02115
Site 41
Chicago, Illinois, 60611
Site 17
Columbus, Ohio, 43210
Site 51
Dallas, Texas, 75390
Site 3
El Paso, Texas, 79935
Site 31
Everett, Washington, 98201
Site 65
Houston, Texas, 77079
Site 7
Indianapolis, Indiana, 46202
Site 4
Jackson, Mississippi, 39202
Site 6
Jamaica, New York, 11432
Site 36
Los Angeles, California, 90095
Site 2
Metairie, Louisiana, 70006
Site 10
Miami, Florida, 33136
Site 57
New York, New York, 10021
Site 35
New York, New York, 10029
Site 39
New York, New York, 10065
Site 11
Oklahoma City, Oklahoma, 73104
Site 53
Omaha, Nebraska, 68198
Site 62
Philadelphia, Pennsylvania, 19107
Site 21
Phoenix, Arizona, 85013
Site 19
Pittsburgh, Pennsylvania, 15212
Site 71
Pittsburgh, Pennsylvania, 15213
Site 72
Reno, Nevada, 89511
Site 56
Shavano Park, Texas, 78231
Site 13
St Louis, Missouri, 63110
Site 5
Summerville, South Carolina, 29485
Site 68
Torrance, California, 90502
Site 1
Wilmington, North Carolina, 28401
Italy8 sites
Site 43
Ancona, 60030
Site 15
Messina, 98125
Site 26
Milan, 20149
Site 12
Naples, 80131
Site 38
Orbassano, 10043
Site 67
Padova, 35128
Site 40
Roma, 00161
Site 16
Roma, 00189
Spain5 sites
Site 75
Alicante, 03010
Site 25
Girona, 17007
Site 24
Madrid, 28007
Site 22
Málaga, 29006
Site 23
Seville, 41013
Israel4 sites
Site 30
Jerusalem, 911120
Site 29
Kfar Saba, 4428164
Site 28
Petah Tikva, 4941480
Site 69
Tel Aviv
Poland4 sites
Site 77
Bialystok
Site 37
Chrzanów, 32-500
Site 59
Krakow, 31- 501
Site 33
Lublin, 20-412
Romania4 sites
Site 66
Bucharest, 010825
Site 63
Bucharest, 011863
Site 64
Bucharest, 011863
Site 73
Iași, 700106
About this study
Official title: Glucocorticoid Receptor Antagonism in the Treatment of Cushing Syndrome (GRACE): A Phase 3, Double-Blind, Placebo-Controlled, Randomized-Withdrawal Study of the Efficacy and Safety of Relacorilant
This is a Phase 3, double-blind, placebo-controlled, randomized-withdrawal study to assess the efficacy, safety and pharmacokinetics (PK) of relacorilant in patients with endogenous Cushing syndrome and concurrent type 2 diabetes mellitus/impaired glucose tolerance (DM/IGT) and/or uncontrolled hypertension (HTN).
Read the detailed description
The primary outcome is the assessment of efficacy of relacorilant treatment based on sustained blood pressure control during the Randomized-withdrawal (RW) Phase, wherein patients who had achieved the blood pressure response criteria during the Open-label (OL) Phase are randomized to receive either relacorilant or placebo for 12 weeks.
Patients in the OL Phase will dose-escalate in 100 mg increments to a maximum dose of 400 mg orally once daily. Patients will remain on OL treatment until Week 22 at which time they will be evaluated for the RW Phase based on predefined hyperglycemia and hypertension response criteria. Eligible patients will then be randomized to receive either relacorilant or placebo at a 1:1 ratio for 12 weeks. Patients who do not meet the criteria for the RW Phase will end treatment and may be eligible to roll over into an extension safety study. Patients who complete the RW Phase of the study may also be eligible to roll over into an extension study.
- Conditions
- Cushing Syndrome
- Being tested
- Relacorilant, Placebo
- Keywords
- Cushing syndrome, Cushing disease, Hypercortisolemia, Cushingoid, Type 2 Diabetes, Impaired Glucose Intolerance, Hypertension, Adrenocorticotropic hormone, Primary Pigmented Nodular Adrenal Disease, Moon Facies, Dorsocervical Fat Pad, Adrenal Adenoma, Adrenal Autonomy, Cortisol, Cushing
- Medical subject headings
- Cushing Syndrome, Pituitary ACTH Hypersecretion, ACTH Syndrome, Ectopic, Diabetes Mellitus, Type 2, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RelacorilantDrug
Also called CORT125134
Relacorilant is supplied as 100 mg capsules for oral dosing.
PlaceboOther
Placebo matched to study drug
| Study group | Role | What they receive |
|---|---|---|
| Relacorilant (OL Phase) | Experimental | Patients will receive relacorilant increased sequentially from 100 mg once daily to a maximum dose of 400 mg once daily. Receives: Drug: Relacorilant |
| Relacorilant (RW Phase) | Experimental | Patients who meet any of the response criteria will advance to the RW Phase of the study and receive the same dose of relacorilant as the last dose administered in the OL Phase. Receives: Drug: Relacorilant |
| Placebo (RW Phase) | Placebo comparator | Patients who meet any of the response criteria will advance to the RW Phase of the study and receive placebo matched to study drug. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase.
Loss of response with respect to HTN was measured using 6 criteria: 1) an increase in SBP of at least 5 mm Hg, 2) an increase in DBP of at least 5 mm Hg, 3) an increase in SBP and/or DBP of at least 5 mm Hg, 4) use of HTN rescue medication, 5) treatment discontinuation, and 6) missing 24-hour ambulatory blood pressure monitoring (ABPM) measurement at the end of the RW Phase. Blood pressure was measured using ABPM. Use of rescue medication was defined as any increase, modification, or addition of antihypertensive medication due to worsening HTN. Treatment discontinuation reports the number of patients who discontinued study treatment in the RW Phase for any reason.
Measured: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Number of Patients With 1 or More Treatment-emergent Adverse Events (TEAEs) as Graded by CTCAE v5.0.
Measured: OL Phase: Up to 22 weeks; RW Phase: up to 18 weeks after completion of the OL Phase
Secondary outcomes (6)
Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose) During the RW Phase
Measured: Before and at time intervals up to 2 hours post glucose drink at Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Change in Hemoglobin HbA1c During the RW Phase
Measured: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Change in 2-hour Plasma Glucose During the RW Phase
Plasma glucose was measured using the 2-hour Oral Glucose Tolerance Test (oGTT).
Measured: Before and 2 hours post glucose drink at Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Change in SBP and DBP During the RW Phase
Blood pressure was measured by 24-hour ABPM.
Measured: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Change in Body Weight During the RW Phase
Measured: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Number of Patients With Any Increase or Modification in Diabetes Medication During the RW Phase
Measured: Week 22 (end of OL Phase) and up to Week 36 (Week 12 of RW Phase)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2018
- Study start15 Nov 2018
- Primary completion8 Apr 2024
- Study completion15 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cushing SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 152 participants (actual)
Sponsor and investigators
- Lead sponsor
- Corcept Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Andreas Moraitis, MD, Study director, Corcept Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03697109
- Sponsor's protocol ID
- CORT125134-455
- Acronym
- GRACE
- Status last verified
- Apr 2025
- First submitted
- 27 Sep 2018
- Last updated
- 16 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pivonello R, Arnaldi G, Auchus RJ, Badiu C, Busch RS, Cannavo S, Dischinger U, Dobri GA, Donegan DM, Elenkova A, Fazeli PK, Feelders RA, Garcia-Centeno R, Gilis-Januszewska A, Hamidi O, Hannoush ZC, Kargi AY, Miller HJ, Ranetti AE, Recasens M, Reincke M, Rovner S, Salvatori R, Silverstein J, Stigliano A, Terzolo M, Wang C, Yuen KCJ, Kesner-Hays A, Hand AL, Tudor IC, Araque KA, Moraitis AG; GRACE Study Investigators. Efficacy and safety of relacorilant for the treatment of patients with Cushing's syndrome (GRACE): a multicentre, phase 3, double-blind, placebo-controlled, randomised-withdrawal study. Lancet Diabetes Endocrinol. 2026 Apr;14(4):291-304. doi: 10.1016/S2213-8587(25)00362-6. Epub 2026 Feb 20.
PubMed 41730814Pivonello 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.
PubMed 35058882
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glucocorticoid Receptor Antagonism in the Treatment of Cushing Syndrome (GRACE): A Phase 3, Double-Blind, Placebo-Controlled, Randomized-Withdrawal Study of the Efficacy and Safety of Relacorilant
- ClinicalTrials.gov ID
- NCT03697109
- Acronym / sponsor ID
- GRACE / CORT125134-455
- Conditions
- Cushing Syndrome
- Keywords
- Cushing syndrome, Cushing disease, Hypercortisolemia, Cushingoid, Type 2 Diabetes, Impaired Glucose Intolerance, Hypertension, Adrenocorticotropic hormone
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 152 participants (actual)
- Lead sponsor
- Corcept TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 15 Nov 2018 (actual)
- Primary completion
- 8 Apr 2024 (actual)
- Study completion
- 15 Apr 2024 (actual)
- First posted
- 5 Oct 2018 (actual)
- Results
- Posted 24 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 3, double-blind, placebo-controlled, randomized-withdrawal study to assess the efficacy, safety and pharmacokinetics (PK) of relacorilant in patients with endogenous Cushing syndrome and concurrent type 2 diabetes mellitus/impaired glucose tolerance (DM/IGT) and/or uncontrolled hypertension (HTN).
Detailed description
The primary outcome is the assessment of efficacy of relacorilant treatment based on sustained blood pressure control during the Randomized-withdrawal (RW) Phase, wherein patients who had achieved the blood pressure response criteria during the Open-label (OL) Phase are randomized to receive either relacorilant or placebo for 12 weeks.
Patients in the OL Phase will dose-escalate in 100 mg increments to a maximum dose of 400 mg orally once daily. Patients will remain on OL treatment until Week 22 at which time they will be evaluated for the RW Phase based on predefined hyperglycemia and hypertension response criteria. Eligible patients will then be randomized to receive either relacorilant or placebo at a 1:1 ratio for 12 weeks. Patients who do not meet the criteria for the RW Phase will end treatment and may be eligible to roll over into an extension safety study. Patients who complete the RW Phase of the study may also be eligible to roll over into an extension study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Relacorilant (OL Phase) | Experimental | Drug: RelacorilantPatients will receive relacorilant increased sequentially from 100 mg once daily to a maximum dose of 400 mg once daily. |
| Relacorilant (RW Phase) | Experimental | Drug: RelacorilantPatients who meet any of the response criteria will advance to the RW Phase of the study and receive the same dose of relacorilant as the last dose administered in the OL Phase. |
| Placebo (RW Phase) | Placebo comparator | Other: PlaceboPatients who meet any of the response criteria will advance to the RW Phase of the study and receive placebo matched to study drug. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Has a confirmed diagnosis of endogenous Cushing syndrome
- Meets at least 1 of the following criteria:
Key exclusion criteria (5 listed)
- Has non-endogenous source of hypercortisolism
- Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism
- Has poorly controlled hypertension
- Has poorly controlled diabetes mellitus
- Has severe renal insufficiency.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RelacorilantAlso: CORT125134Relacorilant is supplied as 100 mg capsules for oral dosing. | Drug | Relacorilant (OL Phase), Relacorilant (RW Phase) |
| PlaceboPlacebo matched to study drug | Other | Placebo (RW Phase) |
Primary outcome
Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase.
Time frame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Loss of response with respect to HTN was measured using 6 criteria: 1) an increase in SBP of at least 5 mm Hg, 2) an increase in DBP of at least 5 mm Hg, 3) an increase in SBP and/or DBP of at least 5 mm Hg, 4) use of HTN rescue medication, 5) treatment discontinuation, and 6) missing 24-hour ambulatory blood pressure monitoring (ABPM) measurement at the end of the RW Phase. Blood pressure was measured using ABPM. Use of rescue medication was defined as any increase, modification, or addition of antihypertensive medication due to worsening HTN. Treatment discontinuation reports the number of patients who discontinued study treatment in the RW Phase for any reason.
Number of Patients With 1 or More Treatment-emergent Adverse Events (TEAEs) as Graded by CTCAE v5.0.
Time frame: OL Phase: Up to 22 weeks; RW Phase: up to 18 weeks after completion of the OL Phase
6 secondary outcomes
Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose) During the RW Phase
Time frame: Before and at time intervals up to 2 hours post glucose drink at Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Change in Hemoglobin HbA1c During the RW Phase
Time frame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Change in 2-hour Plasma Glucose During the RW Phase
Time frame: Before and 2 hours post glucose drink at Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Change in SBP and DBP During the RW Phase
Time frame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Change in Body Weight During the RW Phase
Time frame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Number of Patients With Any Increase or Modification in Diabetes Medication During the RW Phase
Time frame: Week 22 (end of OL Phase) and up to Week 36 (Week 12 of RW Phase)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41730814Pivonello R, Arnaldi G, Auchus RJ, Badiu C, Busch RS, Cannavo S, Dischinger U, Dobri GA, Donegan DM, Elenkova A, Fazeli PK, Feelders RA, Garcia-Centeno R, Gilis-Januszewska A, Hamidi O, Hannoush ZC, Kargi AY, Miller HJ, Ranetti AE, Recasens M, Reincke M, Rovner S, Salvatori R, Silverstein J, Stigliano A, Terzolo M, Wang C, Yuen KCJ, Kesner-Hays A, Hand AL, Tudor IC, Araque KA, Moraitis AG; GRACE Study Investigators. Efficacy and safety of relacorilant for the treatment of patients with Cushing's syndrome (GRACE): a multicentre, phase 3, double-blind, placebo-controlled, randomised-withdrawal study. Lancet Diabetes Endocrinol. 2026 Apr;14(4):291-304. doi: 10.1016/S2213-8587(25)00362-6. Epub 2026 Feb 20.
- Derived from this study: PubMed 35058882Pivonello 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andreas Moraitis, MD study director
Corcept Therapeutics
64 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Relacorilant in people with Cushing Syndrome, run by Corcept Therapeutics at 64 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 64 sites in United States, Italy, Spain, Israel, Poland and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase. (time frame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03697109, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2025.