Cushing Syndrome
Conditions
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
Brief 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).
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.
Interventions
DRUGRelacorilant
Relacorilant is supplied as 100 mg capsules for oral dosing.
OTHERPlacebo
Placebo matched to study drug
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
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase. | 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. | OL Phase: Up to 22 weeks; RW Phase: up to 18 weeks after completion of the OL Phase | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in 2-hour Plasma Glucose During the RW Phase | Before and 2 hours post glucose drink at Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase) | Plasma glucose was measured using the 2-hour Oral Glucose Tolerance Test (oGTT). |
| Change in SBP and DBP During the RW Phase | Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase) | Blood pressure was measured by 24-hour ABPM. |
| Change in Body Weight During the RW Phase | 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 | Week 22 (end of OL Phase) and up to Week 36 (Week 12 of RW Phase) | — |
| Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose) During the RW Phase | 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 | Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase) | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Worsened, as Assessed by the Global Clinical Response, During the RW Phase | Week 22 (end of OL Phase) and up to Week 36 (Week 12 of RW Phase) | The Global Clinical Response assessment measures the patient's signs and symptoms of endogenous hypercortisolism in 7 clinical categories: 1) glucose parameters, 2) blood pressure parameters, 3) body composition parameters, 4) clinical appearance, 5) strength parameters, 6) psychiatric health/cognitive function parameters, and 7) quality of life using the Cushing QoL score. The overall response based on the totality of signs and symptoms is rated as +1 for improved, 0 for unchanged, and -1 for worsened. Each patient's final score is the median of ratings given by 3 members of the Data Review Board. |
| Change in Percent Tissue Fat Mass During the OL Phase | Baseline and Week 22 (end of OL Phase) | Tissue fat mass was measured by DXA scan. |
| Change in Cushing QoL Normalized Total Score During the OL Phase | Baseline and Week 22 (end of OL Phase) | The Cushing QoL patient questionnaire, which evaluates the health-related QoL in patients with Cushing syndrome, comprises 12 questions, each with 5 possible answers. The total score ranges from 12-60, with a higher score indicating improvement in QoL. The Cushing QoL instrument addresses known problem areas associated with Cushing syndrome including trouble sleeping, wound healing/bruising, irritability/mood swings/anger, self-confidence, physical changes, ability to participate in activities, interactions with friends and family, memory issues, and future health concerns. |
| Change in Beck Depression Inventory-II (BDI-II) Score During the OL Phase | Baseline and Week 22 (end of OL Phase) | The BDI-II is a 21-question self-report inventory that measures depression. Each answer is scored with values of 0 to 3. The total score ranges from 0 to 63. Scores of 0 to 13 indicate minimal depression, 14 to 19; mild depression; 20 to 28; moderate depression; 29 to 63; severe depression. |
| Mean Change From Baseline in Body Weight During the OL Phase | Baseline and Week 22 (end of OL Phase) | — |
| Change in 2-hour Plasma Glucose During the OL Phase | Baseline and Week 22 (end of OL Phase) | Plasma glucose was measured using the 2-hour oGTT. |
| Change in Hemoglobin HbA1c During the OL Phase | Baseline and Week 22 (end of OL Phase) | — |
| Change in SBP and DBP During the OL Phase | Baseline and Week 22 (end of OL Phase) | Blood pressure was measured by 24-hour ABPM. |
| Percent Change in Tissue Fat Mass During the RW Phase | Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase) | Tissue fat mass was measured by dual energy X-ray absorptiometry (DXA) scan. Reported are change in in absolute tissue fat mass and change in percent tissue fat mass. |
| Change in Cushing Quality of Life (QoL) Normalized Total Score During the RW Phase | Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase) | The Cushing QoL patient questionnaire, which evaluates the health-related QoL in patients with Cushing syndrome, comprises 12 questions, each with 5 possible answers. The total score ranges from 12-60, with a higher score indicating improvement in QoL. The Cushing QoL instrument addresses known problem areas associated with Cushing syndrome including trouble sleeping, wound healing/bruising, irritability/mood swings/anger, self-confidence, physical changes, ability to participate in activities, interactions with friends and family, memory issues, and future health concerns. |
Countries
Austria, Bulgaria, Canada, Germany, Israel, Italy, Netherlands, Poland, Romania, Spain, United States
Participant flow
Pre-assignment details
A total of 404 patients were screened and 152 were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Relacorilant (OL Phase) Patients will receive relacorilant increased sequentially from 100 mg once daily to a maximum dose of 400 mg once daily.
Relacorilant: Relacorilant is supplied as 100 mg capsules for oral dosing. | 152 |
| Total | 152 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Open-label (OL) Phase | Adverse Event | 24 | 0 | 0 |
| Open-label (OL) Phase | Death | 2 | 0 | 0 |
| Open-label (OL) Phase | Lack of Efficacy | 6 | 0 | 0 |
| Open-label (OL) Phase | Lost to Follow-up | 2 | 0 | 0 |
| Open-label (OL) Phase | Physician Decision | 2 | 0 | 0 |
| Open-label (OL) Phase | Withdrawal by Subject | 21 | 0 | 0 |
| Randomized-withdrawal (RW) Phase | Adverse Event | 0 | 1 | 0 |
| Randomized-withdrawal (RW) Phase | Lack of Efficacy | 0 | 1 | 0 |
| Randomized-withdrawal (RW) Phase | Withdrawal by Subject | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Relacorilant (OL Phase) |
|---|---|
| Age, Continuous | 50.4 years STANDARD_DEVIATION 13.23 |
| Body Mass Index (BMI) | 34.738 kg/m^2 STANDARD_DEVIATION 32.675 |
| Body weight | 93.77 kg STANDARD_DEVIATION 24.66 |
| Diabetes mellitus (DM) or impaired glucose tolerance (IGT) only | 50 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 123 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| HTN and DM/IGT | 71 Participants |
| Hypertension (HTN) only | 31 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants |
| Race (NIH/OMB) More than one race | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) White | 121 Participants |
| Sex: Female, Male Female | 127 Participants |
| Sex: Female, Male Male | 25 Participants |
| Waist circumference | 114.85 cm STANDARD_DEVIATION 18.0355 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 152 | 0 / 30 | 0 / 32 |
| other Total, other adverse events | 147 / 152 | 22 / 30 | 27 / 32 |
| serious Total, serious adverse events | 29 / 152 | 5 / 30 | 1 / 32 |
Outcome results
Primary
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
Population: The analysis population was patients in the Safety Population, which included all enrolled patients who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Relacorilant (RW Phase) | Number of Patients With 1 or More Treatment-emergent Adverse Events (TEAEs) as Graded by CTCAE v5.0. | 147 Participants |
| Placebo (RW Phase) | Number of Patients With 1 or More Treatment-emergent Adverse Events (TEAEs) as Graded by CTCAE v5.0. | 23 Participants |
| Placebo (RW Phase) | Number of Patients With 1 or More Treatment-emergent Adverse Events (TEAEs) as Graded by CTCAE v5.0. | 27 Participants |
Primary
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.
Time frame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Population: The analysis population was patients in the Intent-to-Treat (ITT-RW) Population who met the HTN response criteria at conclusion of the OL Phase. The ITT-RW Population included all patients who were randomized in the RW Phase and received at least 1 dose of study drug post randomization.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Relacorilant (RW Phase) | Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase. | SBP | 3 Participants |
| Relacorilant (RW Phase) | Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase. | SBP and/or DBP | 3 Participants |
| Relacorilant (RW Phase) | Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase. | DBP | 1 Participants |
| Relacorilant (RW Phase) | Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase. | Use of rescue medication | 0 Participants |
| Relacorilant (RW Phase) | Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase. | Treatment discontinuation | 2 Participants |
| Relacorilant (RW Phase) | Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase. | Missing ABPM at end of RW Phase | 2 Participants |
| Placebo (RW Phase) | Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase. | Treatment discontinuation | 3 Participants |
| Placebo (RW Phase) | Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase. | Use of rescue medication | 7 Participants |
| Placebo (RW Phase) | Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase. | SBP | 1 Participants |
| Placebo (RW Phase) | Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase. | Missing ABPM at end of RW Phase | 3 Participants |
| Placebo (RW Phase) | Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase. | DBP | 1 Participants |
| Placebo (RW Phase) | Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase. | SBP and/or DBP | 4 Participants |
Comparison: A logistic regression model with logit link function was used in order to detect if there was a significant difference in total number of patients with a loss of response with respect to HTN under treatment with relacorilant compared with treatment with placebo in the RW Phase.p-value: 0.021595% CI: [0.04, 0.77]Chi-squared
Secondary
Change in 2-hour Plasma Glucose During the RW Phase
Plasma glucose was measured using the 2-hour Oral Glucose Tolerance Test (oGTT).
Time frame: Before and 2 hours post glucose drink at Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Population: The analysis population was patients in the ITT-RW Population who had DM/IGT with or without HTN at Baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Relacorilant (RW Phase) | Change in 2-hour Plasma Glucose During the RW Phase | 0.52 mmol/L |
| Placebo (RW Phase) | Change in 2-hour Plasma Glucose During the RW Phase | 2.96 mmol/L |
Secondary
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)
Population: The analysis population was patients in the ITT-RW Population who had DM/IGT with or without HTN at Baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Relacorilant (RW Phase) | Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose) During the RW Phase | 1.91 hours x mmol/L |
| Placebo (RW Phase) | Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose) During the RW Phase | 4.81 hours x mmol/L |
Secondary
Change in Body Weight During the RW Phase
Time frame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Population: The analysis population was patients in the ITT-RW Population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Relacorilant (RW Phase) | Change in Body Weight During the RW Phase | -1.21 kg |
| Placebo (RW Phase) | Change in Body Weight During the RW Phase | 0.54 kg |
Secondary
Change in Hemoglobin HbA1c During the RW Phase
Time frame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Population: The analysis population was patients in the ITT-RW Population who had DM/IGT with or without HTN at Baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Relacorilant (RW Phase) | Change in Hemoglobin HbA1c During the RW Phase | 0.06 Percentage |
| Placebo (RW Phase) | Change in Hemoglobin HbA1c During the RW Phase | 0.28 Percentage |
Secondary
Change in SBP and DBP During the RW Phase
Blood pressure was measured by 24-hour ABPM.
Time frame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Population: The analysis population was patients in the ITT-RW Population who had HTN with or without DM/IGT at Baseline.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Relacorilant (RW Phase) | Change in SBP and DBP During the RW Phase | SBP | 3.95 mm Hg |
| Relacorilant (RW Phase) | Change in SBP and DBP During the RW Phase | DBP | 2.86 mm Hg |
| Placebo (RW Phase) | Change in SBP and DBP During the RW Phase | DBP | 6.53 mm Hg |
| Placebo (RW Phase) | Change in SBP and DBP During the RW Phase | SBP | 10.43 mm Hg |
Secondary
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)
Population: The analysis population was patients in the ITT-RW Population who had DM/IGT at Baseline and received antidiabetic medication during the RW Phase.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Relacorilant (RW Phase) | Number of Patients With Any Increase or Modification in Diabetes Medication During the RW Phase | 1 Participants |
| Placebo (RW Phase) | Number of Patients With Any Increase or Modification in Diabetes Medication During the RW Phase | 0 Participants |
Other Pre-specified
Change in 2-hour Plasma Glucose During the OL Phase
Plasma glucose was measured using the 2-hour oGTT.
Time frame: Baseline and Week 22 (end of OL Phase)
Population: The analysis population was patients in the mITT-OL Population who had DM/IGT with or without HTN at Baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relacorilant (RW Phase) | Change in 2-hour Plasma Glucose During the OL Phase | Baseline oGTT | 14.370 mmol/L | Standard Deviation 4.9402 |
| Relacorilant (RW Phase) | Change in 2-hour Plasma Glucose During the OL Phase | Change from Baseline in oGTT at Week 22 | -2.117 mmol/L | Standard Deviation 4.6354 |
Other Pre-specified
Change in Beck Depression Inventory-II (BDI-II) Score During the OL Phase
The BDI-II is a 21-question self-report inventory that measures depression. Each answer is scored with values of 0 to 3. The total score ranges from 0 to 63. Scores of 0 to 13 indicate minimal depression, 14 to 19; mild depression; 20 to 28; moderate depression; 29 to 63; severe depression.
Time frame: Baseline and Week 22 (end of OL Phase)
Population: The analysis population was patients in the mITT-OL Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relacorilant (RW Phase) | Change in Beck Depression Inventory-II (BDI-II) Score During the OL Phase | Baseline BDI-II Score | 16.0 score on a scale | Standard Deviation 10.24 |
| Relacorilant (RW Phase) | Change in Beck Depression Inventory-II (BDI-II) Score During the OL Phase | Change from Baseline in BDI-II Score at Week 22 | -2.8 score on a scale | Standard Deviation 8.91 |
Other Pre-specified
Change in Cushing QoL Normalized Total Score During the OL Phase
The Cushing QoL patient questionnaire, which evaluates the health-related QoL in patients with Cushing syndrome, comprises 12 questions, each with 5 possible answers. The total score ranges from 12-60, with a higher score indicating improvement in QoL. The Cushing QoL instrument addresses known problem areas associated with Cushing syndrome including trouble sleeping, wound healing/bruising, irritability/mood swings/anger, self-confidence, physical changes, ability to participate in activities, interactions with friends and family, memory issues, and future health concerns.
Time frame: Baseline and Week 22 (end of OL Phase)
Population: The analysis population was patients in the mITT-OL Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relacorilant (RW Phase) | Change in Cushing QoL Normalized Total Score During the OL Phase | Baseline Cushing QoL Score | 41.9 score on a scale | Standard Deviation 19.78 |
| Relacorilant (RW Phase) | Change in Cushing QoL Normalized Total Score During the OL Phase | Change from Baseline in Cushing QoL Score | 7.4 score on a scale | Standard Deviation 14.63 |
Other Pre-specified
Change in Cushing Quality of Life (QoL) Normalized Total Score During the RW Phase
The Cushing QoL patient questionnaire, which evaluates the health-related QoL in patients with Cushing syndrome, comprises 12 questions, each with 5 possible answers. The total score ranges from 12-60, with a higher score indicating improvement in QoL. The Cushing QoL instrument addresses known problem areas associated with Cushing syndrome including trouble sleeping, wound healing/bruising, irritability/mood swings/anger, self-confidence, physical changes, ability to participate in activities, interactions with friends and family, memory issues, and future health concerns.
Time frame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Population: The analysis population was patients in the ITT-RW Population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Relacorilant (RW Phase) | Change in Cushing Quality of Life (QoL) Normalized Total Score During the RW Phase | 0.59 score on a scale |
| Placebo (RW Phase) | Change in Cushing Quality of Life (QoL) Normalized Total Score During the RW Phase | -0.58 score on a scale |
Other Pre-specified
Change in Hemoglobin HbA1c During the OL Phase
Time frame: Baseline and Week 22 (end of OL Phase)
Population: The analysis population was patients in the mITT-OL Population who had DM/IGT at Baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relacorilant (RW Phase) | Change in Hemoglobin HbA1c During the OL Phase | Baseline HbA1c | 7.16 Percentage | Standard Deviation 1.626 |
| Relacorilant (RW Phase) | Change in Hemoglobin HbA1c During the OL Phase | Change from Baseline in HbA1c at Week 22 | -0.29 Percentage | Standard Deviation 1.014 |
Other Pre-specified
Change in Percent Tissue Fat Mass During the OL Phase
Tissue fat mass was measured by DXA scan.
Time frame: Baseline and Week 22 (end of OL Phase)
Population: The analysis population was patients in the modified ITT-OL (mITT-OL) Population including all enrolled patients who received at least 1 dose of study drug and had at least 1 postbaseline efficacy assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relacorilant (RW Phase) | Change in Percent Tissue Fat Mass During the OL Phase | Baseline Percent Tissue Fat Mass | 46.4 Percentage | Standard Deviation 8.39 |
| Relacorilant (RW Phase) | Change in Percent Tissue Fat Mass During the OL Phase | Change from Baseline in Percent Tissue Fat Mass at Week 22 | -1.8 Percentage | Standard Deviation 2.73 |
Other Pre-specified
Change in SBP and DBP During the OL Phase
Blood pressure was measured by 24-hour ABPM.
Time frame: Baseline and Week 22 (end of OL Phase)
Population: The analysis population was patients in the mITT-OL Population who had HTN at Baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relacorilant (RW Phase) | Change in SBP and DBP During the OL Phase | Baseline SBP | 140.66 mm Hg | Standard Deviation 10.66 |
| Relacorilant (RW Phase) | Change in SBP and DBP During the OL Phase | Change from Baseline in SBP at Week 22 | -7.9 mm Hg | Standard Deviation 9.78 |
| Relacorilant (RW Phase) | Change in SBP and DBP During the OL Phase | Baseline DBP | 88.9 mm Hg | Standard Deviation 7.2 |
| Relacorilant (RW Phase) | Change in SBP and DBP During the OL Phase | Change from Baseline in DBP at Week 22 | -5.4 mm Hg | Standard Deviation 6.98 |
Other Pre-specified
Mean Change From Baseline in Body Weight During the OL Phase
Time frame: Baseline and Week 22 (end of OL Phase)
Population: The analysis population was patients in the mITT-OL Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relacorilant (RW Phase) | Mean Change From Baseline in Body Weight During the OL Phase | Baseline Body Weight | 93.82 kg | Standard Deviation 24.734 |
| Relacorilant (RW Phase) | Mean Change From Baseline in Body Weight During the OL Phase | Change from Baseline in Body Weight at Week 22 | -3.31 kg | Standard Deviation 5.861 |
Other Pre-specified
Number of Patients Who Worsened, as Assessed by the Global Clinical Response, During the RW Phase
The Global Clinical Response assessment measures the patient's signs and symptoms of endogenous hypercortisolism in 7 clinical categories: 1) glucose parameters, 2) blood pressure parameters, 3) body composition parameters, 4) clinical appearance, 5) strength parameters, 6) psychiatric health/cognitive function parameters, and 7) quality of life using the Cushing QoL score. The overall response based on the totality of signs and symptoms is rated as +1 for improved, 0 for unchanged, and -1 for worsened. Each patient's final score is the median of ratings given by 3 members of the Data Review Board.
Time frame: Week 22 (end of OL Phase) and up to Week 36 (Week 12 of RW Phase)
Other Pre-specified
Percent Change in Tissue Fat Mass During the RW Phase
Tissue fat mass was measured by dual energy X-ray absorptiometry (DXA) scan. Reported are change in in absolute tissue fat mass and change in percent tissue fat mass.
Time frame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Population: The analysis population was patients in the ITT-RW Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Relacorilant (RW Phase) | Percent Change in Tissue Fat Mass During the RW Phase | Absolute Tissue Fat Mass | -0.64 Percent Change |
| Relacorilant (RW Phase) | Percent Change in Tissue Fat Mass During the RW Phase | Percent Tissue Fat Mass | -0.14 Percent Change |
| Placebo (RW Phase) | Percent Change in Tissue Fat Mass During the RW Phase | Absolute Tissue Fat Mass | 1.67 Percent Change |
| Placebo (RW Phase) | Percent Change in Tissue Fat Mass During the RW Phase | Percent Tissue Fat Mass | 1.66 Percent Change |