Cushing's SyndromePhase 2NCT02804750
Study to Evaluate CORT125134 in Participants With Cushing's Syndrome
A Phase 2 study testing CORT125134 in people with Cushing's Syndrome, run by Corcept Therapeutics at 25 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cushing's Syndrome
- What is being tested?
- CORT125134
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 25 sitesin 5 countries
- Study dates
- Jun 2016to Sep 2018
- Phase
- Phase 2
- 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's syndrome.
- Requires medical treatment of hypercortisolemia.
- Meets at least one of the following criteria:
- Has type 2 diabetes mellitus.
- Has impaired glucose tolerance.
- Has hypertension.
Who cannot join
- Has non-endogenous source of hypercortisolemia
- Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism
- Has poorly controlled hypertension
- Has Stage ≥ 4 renal failure
Trial locations and contacts
25 sites in 5 countries.
25 sites in 5 countries
United States12 sites
Study site
Aurora, Colorado, 80045
Study site
Cleveland, Ohio, 44195
Study site
Covington, Kentucky, 41011
Study site
Fort Lauderdale, Florida, 33312
Study site
Indianapolis, Indiana, 46202
Study site
Laguna Hills, California, 92653
Study site
Miami, Florida, 33136
Study site
New York, New York, 10016
Study site
Pittsburgh, Pennsylvania, 15212
Study site
Richmond, Virginia, 23119
Study site
Rochester, Minnesota, 55905
Study site
St Louis, Missouri, 63110
Italy8 sites
Study site
Cuneo
Study site
Messina
Study site
Milan
Study site
Naples
Study site
Orbassano
Study site
Roma
Study site
Siena
Study site
Torino
About this study
Official title: Phase 2 Study of the Safety and Efficacy of CORT125134 in the Treatment of Endogenous Cushing's Syndrome
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.
Read the 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.
- Conditions
- Cushing's Syndrome
- Being tested
- CORT125134
- 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
- Medical subject headings
- Cushing Syndrome, Pituitary ACTH Hypersecretion, ACTH Syndrome, Ectopic, Diabetes Mellitus, Type 2, Hypertension, Adrenocortical Carcinoma, Adrenal Cortex Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CORT125134Drug
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Low-dose Group | Experimental | 100 mg/day for 4 weeks in Period 1, then 150 mg/day for 4 weeks in Period 2, then 200 mg/day for 4 weeks in Period 3. There was no washout between treatment periods. Period 3 was followed by a 4-week follow-up period. Per-protocol, Group 1 did not participate in treatment Period 4. Receives: Drug: CORT125134 |
| Group 2: High-dose Group | Experimental | 250 mg/day for 4 weeks in Period 1, then 300 mg/day for 4 weeks in Period 2, then 350 mg/day for 4 weeks in Period 3, then 400 mg/day for 4 weeks in Period 4. There was no washout between treatment periods. Period 4 was followed by a 4-week follow-up period. Receives: Drug: CORT125134 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With One or More Adverse Events
All treatment-emergent adverse events were recorded and summarized.
Measured: Group 1: up to Week 16; Group 2: up to Week 20
Percentage of Participants With One or More Severe (≥Grade 3) Adverse Events
All treatment-emergent adverse events with Common Terminology Criteria for Adverse Events (CTCAE) ≥Grade 3 (severe) were recorded and summarized.
Measured: Group 1: up to Week 16; Group 2: up to Week 20
Secondary outcomes (2)
Percentage of Participants With Hypertension Who Experience Improvement in Blood Pressure Following Treatment With CORT125134
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.
Measured: Group 1: Week 12 or last observation; Group 2: Week 16 or last observation
Percentage of Participants With IGT / T2DM Who Experienced a ≥25% Reduction in AUCglucose Following Treatment With CORT125134
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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2016 (estimated)
- Study startJun 2016
- Primary completionSep 2018
- Study completionSep 2018
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's 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Corcept Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Andreas G Moraitis, MD, Study director, Corcept Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02804750
- Sponsor's protocol ID
- CORT125134-451
- Status last verified
- Oct 2019
- First submitted
- 15 Jun 2016
- Last updated
- 15 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 35058882Pivonello 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.
PubMed 34335465
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of the Safety and Efficacy of CORT125134 in the Treatment of Endogenous Cushing's Syndrome
- ClinicalTrials.gov ID
- NCT02804750
- Acronym / sponsor ID
- CORT125134-451
- Conditions
- Cushing's Syndrome
- Keywords
- Cushing's Syndrome, Cushing's Disease, Cushing's, Hypercortisolemia, Cushingoid, Type 2 Diabetes, Impaired Glucose Intolerance, Hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Corcept TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Jun 2016 (actual)
- Primary completion
- Sep 2018 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 17 Jun 2016 (estimated)
- Results
- Posted 25 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1: Low-dose Group | Experimental | Drug: CORT125134100 mg/day for 4 weeks in Period 1, then 150 mg/day for 4 weeks in Period 2, then 200 mg/day for 4 weeks in Period 3. There was no washout between treatment periods. Period 3 was followed by a 4-week follow-up period. Per-protocol, Group 1 did not participate in treatment Period 4. |
| Group 2: High-dose Group | Experimental | Drug: CORT125134250 mg/day for 4 weeks in Period 1, then 300 mg/day for 4 weeks in Period 2, then 350 mg/day for 4 weeks in Period 3, then 400 mg/day for 4 weeks in Period 4. There was no washout between treatment periods. Period 4 was followed by a 4-week follow-up period. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Has a confirmed diagnosis of endogenous Cushing's syndrome.
- Requires medical treatment of hypercortisolemia.
- Meets at least one of the following criteria:
Key exclusion criteria (4 listed)
- Has non-endogenous source of hypercortisolemia
- Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism
- Has poorly controlled hypertension
- Has Stage ≥ 4 renal failure
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 |
|---|---|---|
| CORT125134 | Drug | Group 1: Low-dose Group, Group 2: High-dose Group |
Primary outcome
Percentage of Participants With One or More Adverse Events
Time frame: 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
Time frame: 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.
2 secondary outcomes
Percentage of Participants With Hypertension Who Experience Improvement in Blood Pressure Following Treatment With CORT125134
Time frame: Group 1: Week 12 or last observation; Group 2: Week 16 or last observation
Percentage of Participants With IGT / T2DM Who Experienced a ≥25% Reduction in AUCglucose Following Treatment With CORT125134
Time frame: 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
- Derived from this study: PubMed 34335465Pivonello 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.
- Individual participant dataSharing planned: No
Related trials for Cushing's Syndrome
Not yet recruitingPhase 2
Osilodrostat for Glycemic Control in Mild Autonomous Cortisol Secretion (MACS) With Difficult-To-Control Type 2 Diabetes - A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study
Mild Autonomous Cortisol Secretion (MACS), Diabetes Mellitus (Type 2)
Active, not recruitingPhase 2
Extension Study to Evaluate the Safety of Long-Term Use of Relacorilant in Patients With Cushing Syndrome
Cushing Syndrome
RecruitingPhase 1/2
Diagnostic Value of CXCR4-targeted PET/CT in ACTH-dependent and Independent Cushing's Syndrome
Cushing s Syndrome
RecruitingPhase 4
Osilodrostat in Patients With Hypertension Caused by Hypercortisolaemia Due to Cushing's Syndrome
Hypertension, Hypercortisolemia
RecruitingObservational study
Collecting Information About Treatment Results for Patients With Cushing's Syndrome
Cushing's Disease, Cushing Syndrome
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 G Moraitis, MD study director
Corcept Therapeutics
25 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CORT125134 in people with Cushing's Syndrome, run by Corcept Therapeutics at 25 sites in 5 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 6 inclusion and 4 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 15 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, Italy, Hungary, Netherlands, United Kingdom. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 25 Sep 2019). 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?
Percentage of Participants With One or More Adverse Events (time frame: Group 1: up to Week 16; Group 2: up to Week 20). 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 NCT02804750, 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 15 Oct 2019.