HypercortisolismPhase 3GRADIENTNCT04308590
A Study of the Efficacy and Safety of Relacorilant in Patients With Cortisol-Secreting Adrenal Adenomas
A Phase 3 study testing Relacorilant in people with Hypercortisolism, run by Corcept Therapeutics at 45 sites in 9 countries.
Trial 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 (DM/IGT) and/or uncontrolled systolic… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hypercortisolism
- 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
- 137 participants
- Where
- 45 sitesin 9 countries
- Study dates
- 27 Jul 2020to 19 Sep 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
- Shows lack of cortisol suppression on dexamethasone suppression test
- Suppressed or low early-morning adrenocorticotropic hormone (ACTH) levels
- A radiologically confirmed adrenal lesion
- Has IGT or DM
- Has uncontrolled HTN
Who cannot join
- Has severe, uncontrolled HTN
- 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
Trial locations and contacts
45 sites in 9 countries.
45 sites in 9 countries
United States22 sites
Site 07
Atlanta, Georgia, 30318
Site 36
Baltimore, Maryland, 21287
Site 27
Birmingham, Alabama, 35294
Site 30
Cleveland, Ohio, 44195
Site 21
Columbus, Ohio, 43201-3209
Site 20
Dallas, Texas, 75390
Site 03
El Paso, Texas, 79935
Site 11
Fall River, Massachusetts, 02721
Site 05
Fort Worth, Texas, 76132
Site 08
Houston, Texas, 77079
Site 16
Indianapolis, Indiana, 46202
Site 06
Jackson, Mississippi, 39202
Site 10
Jamaica, New York, 11432
Site 09
Metairie, Louisiana, 70006
Site 44
New York, New York, 10021
Site 54
Reno, Nevada, 89511
Site 33
Rochester, Minnesota, 55905
Site 15
Spokane, Washington, 99202
Site 17
Stanford, California, 94305
Site 02
Summerville, South Carolina, 29485
Site 53
Torrance, California, 90502
Site 01
Wilmington, North Carolina, 28401
Italy8 sites
Site 40
Milan, Milano, 20122
Site 34
Milan
Site 28
Naples, 80131
Site 43
Orbassano, Torino
Site 51
Padova, 35128
Site 31
Rome, Roma, 00189
Site 37
Rome, 00161
Site 52
Torino, 10126
Romania3 sites
Site 42
Bucharest, 010825
Site 38
Bucharest, 011863
Site 41
Bucharest, 011863
About this study
Official title: Glucocorticoid Receptor Antagonism in the Treatment of Hypercortisolism in Patients With Cortisol-Secreting Adrenal Adenomas or Hyperplasia (GRADIENT): A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Relacorilant
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 (DM/IGT) and/or uncontrolled systolic hypertension (HTN).
Read the detailed description
The primary outcome measures of the study are 1) to assess the efficacy of relacorilant based on blood pressure control at Week 22 compared with placebo, and 2) to assess the safety of relacorilant based on adverse events. 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.
- Conditions
- Hypercortisolism
- Being tested
- Relacorilant, Placebo
- Keywords
- 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
- Medical subject headings
- Cushing Syndrome, 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 blister-packed capsules for oral dosing. Relacorilant 400 mg dose consists of 4 relacorilant 100-mg capsules. Relacorilant 100-mg, 200-mg, and 300-mg doses are each given as a combination of 4 capsules containing relacorilant 100-mg and placebo as per the assigned dose.
PlaceboOther
Placebo is supplied as blister-packed capsules for oral dosing. Each dose consists of 4 capsules containing placebo.
| Study group | Role | What they receive |
|---|---|---|
| Relacorilant | Experimental | Patients will receive relacorilant increased sequentially from 100 mg once daily to a maximum dose of 400 mg once daily. Receives: Drug: Relacorilant; Other: Placebo |
| Placebo | Placebo comparator | Patients will receive placebo matched to study drug once daily. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Average 24-hour SBP
Blood pressure was measured by 24-hour ABPM. The 24-hour average SBP is reported.
Measured: Baseline and Week 22
Number of Patients With 1 or More Treatment-emergent Adverse Events (TEAEs) as Graded by CTCAE v5.0.
Measured: Baseline and up to Week 26
Secondary outcomes (15)
Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose)
AUCglucose was calculated based on results of the plasma 2-hour oGTT.
Measured: Before and at time intervals up to 2 hours post glucose drink at Baseline and Week 22
Change in Average Diastolic Blood Pressure (DBP)
Blood pressure was measured by 24-hour ABPM. Daytime average DBP was measured from 06:00 to 21:59. Nighttime average DBP was measure from 22:00 to 05:59.
Measured: Baseline and Week 22
Change in Average Heart Rate (HR)
Heart rate was measured by 24-hour ABPM. Daytime average HR was measured from 06:00 to 21:59. Nighttime average HR was measure from 22:00 to 05:59.
Measured: Baseline and Week 22
Change in Average Daytime and Nighttime SBP
Blood pressure was measured by 24-hour ABPM. Daytime average SBP was measured from 06:00 to 21:59. Nighttime average SBP was measure from 22:00 to 05:59.
Measured: Baseline and Week 22
Change in Hemoglobin HbA1c for Patients With HbA1c ≥5.7% at Baseline
Measured: Baseline and Week 22
Change in HbA1c for Patients With HbA1c ≥6.5% at Baseline
Measured: Baseline and Week 22
Number of Patients With DM Who Achieved 2-hour oGTT Glucose <140 mg/dL
Glucose was measured using the 2 hour timepoint of the 2-hour oGTT.
Measured: 2 hours post glucose drink at Week 22
Number of Patients With IGT Who Achieved 2-hour oGTT Glucose <140 mg/dL
Glucose was measured using the 2 hour timepoint of the 2-hour oGTT.
Measured: 2 hours post glucose drink at Week 22
Number of Patients With Any Dose Decrease in Antihypertensive Medication
Measured: Baseline and Week 22
Number of Patients With Any Dose Decrease in Diabetes Medication
Measured: Baseline and Week 22
Number of Patients With Any Dose Increase or Switch in Antihypertensive Medication
Measured: Baseline and Week 22
Number of Patients With Any Dose Increase or Switch in Diabetes Medication
Measured: Baseline and Week 22
Number of Patients With HbA1c ≥6.5% at Baseline Who Achieved HbA1c <6.5%
Measured: Baseline and Week 22
Number of Patients With Normalization of the 24-hour Average SBP (<130 mm Hg)
Blood pressure was measured by 24-hour ABPM Test. Reported is the number of patients with HTN at Baseline who achieved SBP <130 mm Hg at Week 22.
Measured: Baseline and Week 22
Number of Patients With a Reduction in 24-hour Average SBP by ≥5 mm Hg
Blood pressure was measured by 24-hour ABPM. Reported is the number of patients with HTN at Baseline who achieved at least a 5 mm Hg reduction in 24-hour average SBP at Week 22.
Measured: Baseline and Week 22
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2020
- Study start27 Jul 2020
- Primary completion19 Sep 2024
- Study completion19 Sep 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.
- Other trials for HypercortisolismStudies 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
- 137 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
- NCT04308590
- Sponsor's protocol ID
- CORT125134-456
- Acronym
- GRADIENT
- Status last verified
- Aug 2025
- First submitted
- 27 Feb 2020
- Last updated
- 4 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glucocorticoid Receptor Antagonism in the Treatment of Hypercortisolism in Patients With Cortisol-Secreting Adrenal Adenomas or Hyperplasia (GRADIENT): A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Relacorilant
- ClinicalTrials.gov ID
- NCT04308590
- Acronym / sponsor ID
- GRADIENT / CORT125134-456
- Conditions
- Hypercortisolism
- Keywords
- Cushing syndrome, Cushing, Hypercortisolemia, Type 2 Diabetes, Impaired Glucose Intolerance, Hypertension, Adrenocorticotropic hormone, Primary Pigmented Nodular Adrenal Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 137 participants (actual)
- Lead sponsor
- Corcept TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 27 Jul 2020 (actual)
- Primary completion
- 19 Sep 2024 (actual)
- Study completion
- 19 Sep 2024 (actual)
- First posted
- 16 Mar 2020 (actual)
- Results
- Posted 3 Aug 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, 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 (DM/IGT) and/or uncontrolled systolic hypertension (HTN).
Detailed description
The primary outcome measures of the study are 1) to assess the efficacy of relacorilant based on blood pressure control at Week 22 compared with placebo, and 2) to assess the safety of relacorilant based on adverse events. 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Relacorilant | Experimental | Drug: Relacorilant, Other: PlaceboPatients will receive relacorilant increased sequentially from 100 mg once daily to a maximum dose of 400 mg once daily. |
| Placebo | Placebo comparator | Other: PlaceboPatients will receive placebo matched to study drug once daily. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Shows lack of cortisol suppression on dexamethasone suppression test
- Suppressed or low early-morning adrenocorticotropic hormone (ACTH) levels
- A radiologically confirmed adrenal lesion
- Has IGT or DM
- Has uncontrolled HTN
Key exclusion criteria (5 listed)
- Has severe, uncontrolled HTN
- 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
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 blister-packed capsules for oral dosing. Relacorilant 400 mg dose consists of 4 relacorilant 100-mg capsules. Relacorilant 100-mg, 200-mg, and 300-mg doses are each given as a combination of 4 capsules containing relacorilant 100-mg and placebo as per the assigned dose. | Drug | Relacorilant |
| PlaceboPlacebo is supplied as blister-packed capsules for oral dosing. Each dose consists of 4 capsules containing placebo. | Other | Placebo, Relacorilant |
Primary outcome
Change in Average 24-hour SBP
Time frame: Baseline and Week 22
Blood pressure was measured by 24-hour ABPM. The 24-hour average SBP is reported.
Number of Patients With 1 or More Treatment-emergent Adverse Events (TEAEs) as Graded by CTCAE v5.0.
Time frame: Baseline and up to Week 26
15 secondary outcomes
Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose)
Time frame: Before and at time intervals up to 2 hours post glucose drink at Baseline and Week 22
Change in Average Diastolic Blood Pressure (DBP)
Time frame: Baseline and Week 22
Change in Average Heart Rate (HR)
Time frame: Baseline and Week 22
Change in Average Daytime and Nighttime SBP
Time frame: Baseline and Week 22
Change in Hemoglobin HbA1c for Patients With HbA1c ≥5.7% at Baseline
Time frame: Baseline and Week 22
Change in HbA1c for Patients With HbA1c ≥6.5% at Baseline
Time frame: Baseline and Week 22
Number of Patients With DM Who Achieved 2-hour oGTT Glucose <140 mg/dL
Time frame: 2 hours post glucose drink at Week 22
Number of Patients With IGT Who Achieved 2-hour oGTT Glucose <140 mg/dL
Time frame: 2 hours post glucose drink at Week 22
Number of Patients With Any Dose Decrease in Antihypertensive Medication
Time frame: Baseline and Week 22
Number of Patients With Any Dose Decrease in Diabetes Medication
Time frame: Baseline and Week 22
Number of Patients With Any Dose Increase or Switch in Antihypertensive Medication
Time frame: Baseline and Week 22
Number of Patients With Any Dose Increase or Switch in Diabetes Medication
Time frame: Baseline and Week 22
Number of Patients With HbA1c ≥6.5% at Baseline Who Achieved HbA1c <6.5%
Time frame: Baseline and Week 22
Number of Patients With Normalization of the 24-hour Average SBP (<130 mm Hg)
Time frame: Baseline and Week 22
Number of Patients With a Reduction in 24-hour Average SBP by ≥5 mm Hg
Time frame: Baseline and Week 22
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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
45 sites in 9 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 Hypercortisolism, run by Corcept Therapeutics at 45 sites in 9 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 4 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in United States, Italy, Poland, Romania, Spain and 4 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 3 Aug 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?
Change in Average 24-hour SBP (time frame: Baseline and Week 22). 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?
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 4 Sep 2025.