Trial Outcomes & Findings for An Oral GnRH Antagonist to Treat Mild Autonomous Cortisol Excess (MACE) Due to Adrenal Adenomas in Postmenopausal Women (NCT NCT05038878)

Results Overview

Cortisol level after dexamethasone suppression test which measures whether adrenocorticotrophic hormone (ACTH) secretion by the pituitary can be suppressed. Number of participants with interval improvement and normalization of late-night salivary results after 6 months of treatment.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

4 participants

Primary outcome timeframe

baseline and 6 months

Results posted on

2025-03-18

Participant Flow

Participant milestones

Participant milestones
Measure	GnRH Antagonist (Elagolix) Post-menopausal women with benign appearing adrenal adenomas, absence of clinical features of overt Cushing's signs or symptoms and MACE confirmed on either 24 hr urine free cortisol (UFC), late night salivary cortisol and/or abnormal dexamethasone suppression Elagolix: Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months
Overall Study STARTED	4
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GnRH Antagonist (Elagolix) n=4 Participants Post-menopausal women with benign appearing adrenal adenomas, absence of clinical features of overt Cushing's signs or symptoms and MACE confirmed on either 24 hr urine free cortisol (UFC), late night salivary cortisol and/or abnormal dexamethasone suppression Elagolix: Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months
Age, Continuous	64.25 years STANDARD_DEVIATION 5.37 • n=4 Participants
Sex: Female, Male Female	4 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: baseline and 6 months

Cortisol level after dexamethasone suppression test which measures whether adrenocorticotrophic hormone (ACTH) secretion by the pituitary can be suppressed. Number of participants with interval improvement and normalization of late-night salivary results after 6 months of treatment.

Outcome measures

Outcome measures
Measure	GnRH Antagonist (Elagolix) n=4 Participants Post-menopausal women with benign appearing adrenal adenomas, absence of clinical features of overt Cushing's signs or symptoms and MACE confirmed on either 24 hr urine free cortisol (UFC), late night salivary cortisol and/or abnormal dexamethasone suppression Elagolix: Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months
Number of Participants With Change in Cortisol Level	2 Participants

PRIMARY outcome

Timeframe: baseline and 6 months

Cortisol level after dexamethasone suppression test which measures whether adrenocorticotrophic hormone (ACTH) secretion by the pituitary can be suppressed. Cortisol secretion as reported below by assessment of pre-treatment and post-treatment of late-night salivary cortisol levels (normal midnight values: \<0.010 - 0.090)

Outcome measures

Outcome measures
Measure	GnRH Antagonist (Elagolix) n=4 Participants Post-menopausal women with benign appearing adrenal adenomas, absence of clinical features of overt Cushing's signs or symptoms and MACE confirmed on either 24 hr urine free cortisol (UFC), late night salivary cortisol and/or abnormal dexamethasone suppression Elagolix: Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months
Change in Cortisol Level Baseline Salivary #1	0.252 ng/mL Interval 0.192 to 0.347
Change in Cortisol Level Baseline Salivary #2	0.092 ng/mL Interval 0.045 to 0.161
Change in Cortisol Level 6 months Salivary #1	0.092 ng/mL Interval 0.053 to 0.124
Change in Cortisol Level 6 months Salivary #2	0.4355 ng/mL Interval 0.035 to 0.78

PRIMARY outcome

Timeframe: Baseline and 6 months

24 hour urine free cortisol measurements. The cortisol urine test measures the level of cortisol in the urine. Cortisol is a glucocorticoid (steroid) hormone produced by the adrenal gland. Number of participants with improvement in 24-hour urinary free cortisol after treatment (normal 24-hr urinary cortisol is between 6 - 42 ug/24 hr).

Outcome measures

Outcome measures
Measure	GnRH Antagonist (Elagolix) n=4 Participants Post-menopausal women with benign appearing adrenal adenomas, absence of clinical features of overt Cushing's signs or symptoms and MACE confirmed on either 24 hr urine free cortisol (UFC), late night salivary cortisol and/or abnormal dexamethasone suppression Elagolix: Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months
Number of Participants With Change in 24 Hour Urine Free Cortisol Level	1 Participants

PRIMARY outcome

Timeframe: Baseline and 6 months

24 hour urine free cortisol measurements. The cortisol urine test measures the level of cortisol in the urine. Cortisol is a glucocorticoid (steroid) hormone produced by the adrenal gland. Cortisol secretion as reported below by assessment of pre-treatment and post-treatment of 24-hour urinary cortisol levels (normal 24-hr urinary cortisol is between 6 - 42 ug/24 hr).

Outcome measures

Outcome measures
Measure	GnRH Antagonist (Elagolix) n=4 Participants Post-menopausal women with benign appearing adrenal adenomas, absence of clinical features of overt Cushing's signs or symptoms and MACE confirmed on either 24 hr urine free cortisol (UFC), late night salivary cortisol and/or abnormal dexamethasone suppression Elagolix: Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months
24 Hour Urine Free Cortisol Level baseline	14 ug/24 hour Interval 13.0 to 66.0
24 Hour Urine Free Cortisol Level 6 months	23 ug/24 hour Interval 12.0 to 32.0

PRIMARY outcome

Timeframe: Baseline and 6 months

All patients will have baseline imaging (CT or MRI) within 6 months to start of treatment and then will have repeat imaging with CT abdomen without contrast at 6 months to determine the effect of elagolix treatment on adrenal adenoma size and imaging characteristics. The images will be reviewed by a dedicated adrenal radiologist for consistency.

Outcome measures

Outcome measures
Measure	GnRH Antagonist (Elagolix) n=4 Participants Post-menopausal women with benign appearing adrenal adenomas, absence of clinical features of overt Cushing's signs or symptoms and MACE confirmed on either 24 hr urine free cortisol (UFC), late night salivary cortisol and/or abnormal dexamethasone suppression Elagolix: Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months
Number of Participants With Change in Adenoma Size as Compared to Baseline	0 Participants

PRIMARY outcome

Timeframe: Baseline and 6 months

All patients will have baseline imaging (CT or MRI) within 6 months to start of treatment and then will have repeat imaging with CT abdomen without contrast at 6 months to determine the effect of elagolix treatment on adrenal adenoma size and imaging characteristics. The images will be reviewed by a dedicated adrenal radiologist for consistency.

Outcome measures

Outcome measures
Measure	GnRH Antagonist (Elagolix) n=4 Participants Post-menopausal women with benign appearing adrenal adenomas, absence of clinical features of overt Cushing's signs or symptoms and MACE confirmed on either 24 hr urine free cortisol (UFC), late night salivary cortisol and/or abnormal dexamethasone suppression Elagolix: Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months
Change in Adenoma Size as Compared to Baseline baseline (MRI) Right	1.78 cm Standard Deviation 0.26
Change in Adenoma Size as Compared to Baseline 6 months (CT) Right	1.8 cm Standard Deviation 0.22
Change in Adenoma Size as Compared to Baseline baseline (MRI) Left	2.33 cm Standard Deviation 1.27
Change in Adenoma Size as Compared to Baseline 6 months (CT) Left	2.13 cm Standard Deviation 1.29

SECONDARY outcome

Timeframe: baseline and 6 months

Mean percent change in body weight is measured in kilograms at 6 months compared to baseline

Outcome measures

Outcome measures
Measure	GnRH Antagonist (Elagolix) n=4 Participants Post-menopausal women with benign appearing adrenal adenomas, absence of clinical features of overt Cushing's signs or symptoms and MACE confirmed on either 24 hr urine free cortisol (UFC), late night salivary cortisol and/or abnormal dexamethasone suppression Elagolix: Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months
Change in Body Weight as Compared to Baseline	1.86 percent change in body weight Standard Deviation 11.4

SECONDARY outcome

Timeframe: baseline and 6 months

Population: Data for participants who lost weight

Mean percent change in body weight is measured in kilograms at 6 months compared to baseline

Outcome measures

Outcome measures
Measure	GnRH Antagonist (Elagolix) n=3 Participants Post-menopausal women with benign appearing adrenal adenomas, absence of clinical features of overt Cushing's signs or symptoms and MACE confirmed on either 24 hr urine free cortisol (UFC), late night salivary cortisol and/or abnormal dexamethasone suppression Elagolix: Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months
Change in Body Weight for Those Participants Who Lost Weight	-3.86 percent change in body weight Standard Deviation 0.6

SECONDARY outcome

Timeframe: baseline and 6 months

Population: Data for participants who completed dexa scan at both timepoints

Trunk Fat composition assessed by DEXA scans at baseline and at 6 months.

Outcome measures

Outcome measures
Measure	GnRH Antagonist (Elagolix) n=2 Participants Post-menopausal women with benign appearing adrenal adenomas, absence of clinical features of overt Cushing's signs or symptoms and MACE confirmed on either 24 hr urine free cortisol (UFC), late night salivary cortisol and/or abnormal dexamethasone suppression Elagolix: Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months
Trunk Fat Baseline	44.7 percent of total fat Standard Deviation 3.9
Trunk Fat 6 months	42.6 percent of total fat Standard Deviation 1.6

SECONDARY outcome

Timeframe: baseline and 6 months

fasting blood sugar

Outcome measures

Outcome measures
Measure	GnRH Antagonist (Elagolix) n=4 Participants Post-menopausal women with benign appearing adrenal adenomas, absence of clinical features of overt Cushing's signs or symptoms and MACE confirmed on either 24 hr urine free cortisol (UFC), late night salivary cortisol and/or abnormal dexamethasone suppression Elagolix: Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months
Preserved Glucose Baseline	136.5 mg/dL Standard Deviation 51.9
Preserved Glucose 6 months	126.75 mg/dL Standard Deviation 41.6

SECONDARY outcome

Timeframe: baseline and 6 months

Number of participants with vertebral fractures to measure rates will be assessed by lateral X-rays of thoracic and lumbar spine.

Outcome measures

Outcome measures
Measure	GnRH Antagonist (Elagolix) n=4 Participants Post-menopausal women with benign appearing adrenal adenomas, absence of clinical features of overt Cushing's signs or symptoms and MACE confirmed on either 24 hr urine free cortisol (UFC), late night salivary cortisol and/or abnormal dexamethasone suppression Elagolix: Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months
Number of Participants With Vertebral Fractures Baseline	0 Participants
Number of Participants With Vertebral Fractures 6 months	0 Participants

SECONDARY outcome

Timeframe: baseline and 6 months

The Cushing's Quality of Life Questionnaire is converted to a 0-100 scale in which 0 indicates the worse and 100 the best possible quality of life.

Outcome measures

Outcome measures
Measure	GnRH Antagonist (Elagolix) n=4 Participants Post-menopausal women with benign appearing adrenal adenomas, absence of clinical features of overt Cushing's signs or symptoms and MACE confirmed on either 24 hr urine free cortisol (UFC), late night salivary cortisol and/or abnormal dexamethasone suppression Elagolix: Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months
The Cushing's Quality of Life Questionnaire 6 months	83 score on a scale Standard Deviation 7.0
The Cushing's Quality of Life Questionnaire baseline	70 score on a scale Standard Deviation 9.2

SECONDARY outcome

Timeframe: baseline and 6 months

Beck's Depression Scale is scored on a scale of 1 to 40, where the higher score indicates severe or extreme depression.

Outcome measures

Outcome measures
Measure	GnRH Antagonist (Elagolix) n=4 Participants Post-menopausal women with benign appearing adrenal adenomas, absence of clinical features of overt Cushing's signs or symptoms and MACE confirmed on either 24 hr urine free cortisol (UFC), late night salivary cortisol and/or abnormal dexamethasone suppression Elagolix: Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months
Beck's Depression Scale baseline	29 score on a scale Standard Deviation 10.1
Beck's Depression Scale 6 months	22 score on a scale Standard Deviation 8.3

SECONDARY outcome

Timeframe: baseline and 6 months

The State Trait Anxiety Inventory gives a score range from 6-24 with the higher score indicating a higher level of anxiety.

Outcome measures

Outcome measures
Measure	GnRH Antagonist (Elagolix) n=4 Participants Post-menopausal women with benign appearing adrenal adenomas, absence of clinical features of overt Cushing's signs or symptoms and MACE confirmed on either 24 hr urine free cortisol (UFC), late night salivary cortisol and/or abnormal dexamethasone suppression Elagolix: Patients will be given Elagolix 200 mg orally twice daily for a total of 6 months
State Trait Anxiety Inventory (STAI) baseline	17 score on a scale Standard Deviation 5.4
State Trait Anxiety Inventory (STAI) 6 months	12 score on a scale Standard Deviation 3.8

Adverse Events

GnRH Antagonist (Elagolix)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Alice C. Levine

Icahn School of Medicine at Mount Sinai

Phone: (212) 241-3422

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place