Hypercortisolism
Conditions
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
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 (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.
Interventions
DRUGRelacorilant
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.
OTHERPlacebo
Placebo is supplied as blister-packed capsules for oral dosing. Each dose consists of 4 capsules containing placebo.
Sponsors
Corcept Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Average 24-hour SBP | 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. | Baseline and up to Week 26 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Average Heart Rate (HR) | Baseline and Week 22 | 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. |
| Change in Average Daytime and Nighttime SBP | Baseline and Week 22 | 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. |
| Change in Hemoglobin HbA1c for Patients With HbA1c ≥5.7% at Baseline | Baseline and Week 22 | — |
| Change in HbA1c for Patients With HbA1c ≥6.5% at Baseline | Baseline and Week 22 | — |
| Number of Patients With DM Who Achieved 2-hour oGTT Glucose <140 mg/dL | 2 hours post glucose drink at Week 22 | Glucose was measured using the 2 hour timepoint of the 2-hour oGTT. |
| Number of Patients With IGT Who Achieved 2-hour oGTT Glucose <140 mg/dL | 2 hours post glucose drink at Week 22 | Glucose was measured using the 2 hour timepoint of the 2-hour oGTT. |
| Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose) | Before and at time intervals up to 2 hours post glucose drink at Baseline and Week 22 | AUCglucose was calculated based on results of the plasma 2-hour oGTT. |
| Number of Patients With Any Dose Decrease in Diabetes Medication | Baseline and Week 22 | — |
| Number of Patients With Any Dose Increase or Switch in Antihypertensive Medication | Baseline and Week 22 | — |
| Number of Patients With Any Dose Increase or Switch in Diabetes Medication | Baseline and Week 22 | — |
| Number of Patients With HbA1c ≥6.5% at Baseline Who Achieved HbA1c <6.5% | Baseline and Week 22 | — |
| Number of Patients With Normalization of the 24-hour Average SBP (<130 mm Hg) | Baseline and Week 22 | 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. |
| Number of Patients With a Reduction in 24-hour Average SBP by ≥5 mm Hg | Baseline and Week 22 | 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. |
| Number of Patients With Any Dose Decrease in Antihypertensive Medication | Baseline and Week 22 | — |
| Change in Average Diastolic Blood Pressure (DBP) | Baseline and Week 22 | 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. |
Countries
Austria, Bulgaria, Germany, Israel, Italy, Poland, Romania, Spain, United States
Participant flow
Pre-assignment details
A total of 307 patients were screened and 137 were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Relacorilant Patients will receive relacorilant increased sequentially from 100 mg once daily to a maximum dose of 400 mg once daily. | 68 |
| Placebo Patients will receive placebo matched to study drug once daily. | 69 |
| Total | 137 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 2 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Subject does not want to continue with Pi | 0 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 4 |
Baseline characteristics
| Characteristic | Placebo | Total | Relacorilant |
|---|---|---|---|
| Age, Continuous | 63.0 years STANDARD_DEVIATION 9 | 62.7 years STANDARD_DEVIATION 9.02 | 62.5 years STANDARD_DEVIATION 9.11 |
| Diabetes mellitus (DM) or impaired glucose tolerance (IGT) only | 27 Participants | 53 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 10 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 63 Participants | 127 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HTN and DM/IGT | 21 Participants | 43 Participants | 22 Participants |
| Hypertension (HTN) only | 21 Participants | 41 Participants | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 65 Participants | 128 Participants | 63 Participants |
| Sex: Female, Male Female | 49 Participants | 99 Participants | 50 Participants |
| Sex: Female, Male Male | 20 Participants | 38 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 68 | 0 / 69 |
| other Total, other adverse events | 65 / 68 | 60 / 69 |
| serious Total, serious adverse events | 15 / 68 | 4 / 69 |
Outcome results
Primary
Change in Average 24-hour SBP
Blood pressure was measured by 24-hour ABPM. The 24-hour average SBP is reported.
Time frame: Baseline and Week 22
Population: The analysis population was patients in the ITT Population who had HTN with or without DM/IGT at Baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Relacorilant | Change in Average 24-hour SBP | -5.56 mm Hg |
| Placebo | Change in Average 24-hour SBP | -2.89 mm Hg |
p-value: 0.41695% CI: [-9.096, 3.766]Mixed Models Analysis
Primary
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
Population: The analysis population was patients in the Safety Population which included all randomized patients who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Relacorilant | Number of Patients With 1 or More Treatment-emergent Adverse Events (TEAEs) as Graded by CTCAE v5.0. | 67 Participants |
| Placebo | Number of Patients With 1 or More Treatment-emergent Adverse Events (TEAEs) as Graded by CTCAE v5.0. | 60 Participants |
Secondary
Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose)
AUCglucose was calculated based on results of the plasma 2-hour oGTT.
Time frame: Before and at time intervals up to 2 hours post glucose drink at Baseline and Week 22
Population: The analysis population was patients in the ITT Population who had DM/IGT with or without HTN at Baseline and had an available assessment at Week 22.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Relacorilant | Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose) | -1.566 hours x mmol/L |
| Placebo | Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose) | 1.008 hours x mmol/L |
Secondary
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.
Time frame: Baseline and Week 22
Population: The analysis population was patients in the ITT Population who had HTN with or without DM/IGT at Baseline and had an available assessment at Week 22.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Relacorilant | Change in Average Daytime and Nighttime SBP | Daytime Average | -4.5 mm Hg |
| Relacorilant | Change in Average Daytime and Nighttime SBP | Nighttime Average | -4.6 mm Hg |
| Placebo | Change in Average Daytime and Nighttime SBP | Daytime Average | -2.5 mm Hg |
| Placebo | Change in Average Daytime and Nighttime SBP | Nighttime Average | -3.0 mm Hg |
Secondary
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.
Time frame: Baseline and Week 22
Population: The analysis population was patients in the ITT Population who had HTN with or without DM/IGT at Baseline and had an available assessment at Week 22.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Relacorilant | Change in Average Diastolic Blood Pressure (DBP) | 24-hour Average | -3.3 mm Hg |
| Relacorilant | Change in Average Diastolic Blood Pressure (DBP) | Daytime Average | -3.1 mm Hg |
| Relacorilant | Change in Average Diastolic Blood Pressure (DBP) | Nighttime Average | -3.0 mm Hg |
| Placebo | Change in Average Diastolic Blood Pressure (DBP) | 24-hour Average | -1.4 mm Hg |
| Placebo | Change in Average Diastolic Blood Pressure (DBP) | Daytime Average | -1.0 mm Hg |
| Placebo | Change in Average Diastolic Blood Pressure (DBP) | Nighttime Average | -0.6 mm Hg |
Secondary
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.
Time frame: Baseline and Week 22
Population: The analysis population was patients in the ITT Population who had HTN with or without DM/IGT at Baseline and had an available assessment at Week 22.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Relacorilant | Change in Average Heart Rate (HR) | 24-hour Average | 2.0 Beats per minute |
| Relacorilant | Change in Average Heart Rate (HR) | Daytime Average | 1.7 Beats per minute |
| Relacorilant | Change in Average Heart Rate (HR) | Nighttime Average | 2.2 Beats per minute |
| Placebo | Change in Average Heart Rate (HR) | 24-hour Average | -2.0 Beats per minute |
| Placebo | Change in Average Heart Rate (HR) | Daytime Average | -1.5 Beats per minute |
| Placebo | Change in Average Heart Rate (HR) | Nighttime Average | -2.7 Beats per minute |
Secondary
Change in HbA1c for Patients With HbA1c ≥6.5% at Baseline
Time frame: Baseline and Week 22
Population: The analysis population was patients in the ITT Population who had DM/IGT with HbA1c ≥6.5% at Baseline and had an available assessment at Week 22.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Relacorilant | Change in HbA1c for Patients With HbA1c ≥6.5% at Baseline | -0.57 Percentage |
| Placebo | Change in HbA1c for Patients With HbA1c ≥6.5% at Baseline | -0.19 Percentage |
Secondary
Change in Hemoglobin HbA1c for Patients With HbA1c ≥5.7% at Baseline
Time frame: Baseline and Week 22
Population: The analysis population was patients in the ITT Population who had DM/IGT with HbA1c ≥5.7% at Baseline and had an available assessment at Week 22.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Relacorilant | Change in Hemoglobin HbA1c for Patients With HbA1c ≥5.7% at Baseline | -0.29 Percentage |
| Placebo | Change in Hemoglobin HbA1c for Patients With HbA1c ≥5.7% at Baseline | 0.00 Percentage |
Secondary
Number of Patients With Any Dose Decrease in Antihypertensive Medication
Time frame: Baseline and Week 22
Population: The analysis population was patients in the ITT Population who had HTN with or without DM/IGT at Baseline, received antihypertension medication both at Baseline and postbaseline, and had an available assessment at Week 22.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Relacorilant | Number of Patients With Any Dose Decrease in Antihypertensive Medication | 7 Participants |
| Placebo | Number of Patients With Any Dose Decrease in Antihypertensive Medication | 5 Participants |
Secondary
Number of Patients With Any Dose Decrease in Diabetes Medication
Time frame: Baseline and Week 22
Population: The analysis population was patients in the ITT Population who had DM/IGT at Baseline, received diabetes medication both at Baseline and postbaseline, and had an available assessment at Week 22.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Relacorilant | Number of Patients With Any Dose Decrease in Diabetes Medication | 0 Participants |
| Placebo | Number of Patients With Any Dose Decrease in Diabetes Medication | 0 Participants |
Secondary
Number of Patients With Any Dose Increase or Switch in Antihypertensive Medication
Time frame: Baseline and Week 22
Population: The analysis population was patients in the ITT Population who had HTN with or without DM/IGT at Baseline, received antihypertension medication both at Baseline and postbaseline, and had an available assessment at Week 22.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Relacorilant | Number of Patients With Any Dose Increase or Switch in Antihypertensive Medication | 1 Participants |
| Placebo | Number of Patients With Any Dose Increase or Switch in Antihypertensive Medication | 5 Participants |
Secondary
Number of Patients With Any Dose Increase or Switch in Diabetes Medication
Time frame: Baseline and Week 22
Population: The analysis population was patients in the ITT Population who had DM/IGT at Baseline, received diabetes medication both at Baseline and postbaseline, and had an available assessment at Week 22.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Relacorilant | Number of Patients With Any Dose Increase or Switch in Diabetes Medication | 4 Participants |
| Placebo | Number of Patients With Any Dose Increase or Switch in Diabetes Medication | 3 Participants |
Secondary
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.
Time frame: Baseline and Week 22
Population: The analysis population was patients in the ITT Population who had HTN with or without DM/IGT at Baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Relacorilant | Number of Patients With a Reduction in 24-hour Average SBP by ≥5 mm Hg | 10 Participants |
| Placebo | Number of Patients With a Reduction in 24-hour Average SBP by ≥5 mm Hg | 13 Participants |
Secondary
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.
Time frame: 2 hours post glucose drink at Week 22
Population: The analysis population was patients in the ITT Population who had DM with or without HTN at Baseline and had an available assessment at Week 22.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Relacorilant | Number of Patients With DM Who Achieved 2-hour oGTT Glucose <140 mg/dL | 1 Participants |
| Placebo | Number of Patients With DM Who Achieved 2-hour oGTT Glucose <140 mg/dL | 0 Participants |
Secondary
Number of Patients With HbA1c ≥6.5% at Baseline Who Achieved HbA1c <6.5%
Time frame: Baseline and Week 22
Population: The analysis population was patients in the ITT Population who had DM with HbA1c ≥6.5% at Baseline and had an available assessment at Week 22.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Relacorilant | Number of Patients With HbA1c ≥6.5% at Baseline Who Achieved HbA1c <6.5% | 3 Participants |
| Placebo | Number of Patients With HbA1c ≥6.5% at Baseline Who Achieved HbA1c <6.5% | 4 Participants |
Secondary
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.
Time frame: 2 hours post glucose drink at Week 22
Population: The analysis population was patients in the ITT Population who had IGT with or without HTN at Baseline and had an available assessment at Week 22.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Relacorilant | Number of Patients With IGT Who Achieved 2-hour oGTT Glucose <140 mg/dL | 6 Participants |
| Placebo | Number of Patients With IGT Who Achieved 2-hour oGTT Glucose <140 mg/dL | 7 Participants |
Secondary
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.
Time frame: Baseline and Week 22
Population: The analysis population was patients in the ITT Population who had HTN with or without DM/IGT at Baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Relacorilant | Number of Patients With Normalization of the 24-hour Average SBP (<130 mm Hg) | 9 Participants |
| Placebo | Number of Patients With Normalization of the 24-hour Average SBP (<130 mm Hg) | 13 Participants |