Trial Outcomes & Findings for Glucocorticoid Receptor Blockade With Mifepristone in Patients With Mild Adrenal Hypercortisolism (NCT NCT01990560)

NCT ID: NCT01990560

Last Updated: 2018-03-02

Results Overview

Change in hyperglycemia assessed by HbA1c, also known as glycated hemoglobin

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 8 participants
• Primary outcome timeframe: Baseline, 3 months, and 6 months
• Results posted on: 2018-03-02

Participant Flow

Participant milestones

Measure	Mifepristone Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Overall Study STARTED	8
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Mifepristone Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Glucocorticoid Receptor Blockade With Mifepristone in Patients With Mild Adrenal Hypercortisolism

Baseline characteristics by cohort

Measure	Mifepristone n=8 Participants Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Age, Continuous	65.5 years STANDARD_DEVIATION 10.6 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 3 months, and 6 months

Change in hyperglycemia assessed by HbA1c, also known as glycated hemoglobin

Outcome measures

Measure	Mifepristone n=8 Participants Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
A1C Level Baseline	6.2 percentage of red blood cells Standard Deviation 0.58
A1C Level 3 months	6.1375 percentage of red blood cells Standard Deviation 0.49
A1C Level 6 months	6.125 percentage of red blood cells Standard Deviation 0.72

PRIMARY outcome

Timeframe: Baseline and 6 months

Population: one participant on insulin. another participant had data missing at 6 months.

Change in hyperglycemia assessed by Homeostatic Model Assessment of Insulin Resistance, HOMA-IR (a validated assessment of insulin resistance). HOMA-IR = fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5.

Outcome measures

Measure	Mifepristone n=6 Participants Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
HOMA-IR Baseline	2.418 HOMA-IR score Standard Deviation 1.64
HOMA-IR 6 months	1.465 HOMA-IR score Standard Deviation 1.19

SECONDARY outcome

Timeframe: Baseline and 6 months

Change in metabolic syndrome as assessed by waist circumference

Outcome measures

Measure	Mifepristone n=8 Participants Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Waist Circumference Baseline	103.25 cm Standard Deviation 17.43
Waist Circumference 6 months	99.3125 cm Standard Deviation 101.25

SECONDARY outcome

Timeframe: Baseline and 6 months

Change in metabolic syndrome as assessed by BMI

Outcome measures

Measure	Mifepristone n=8 Participants Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Body Mass Index (BMI) Baseline	35.1538 kg/m2 Standard Deviation 15.02
Body Mass Index (BMI) 6 months	34.5463 kg/m2 Standard Deviation 15.84

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: one participant data missing at 6 month

Change in metabolic syndrome as assessed by fasting lipid profile which includes Low-density lipoproteins ( LDL), High-density lipoproteins (HDL), and Triglycerides (Trigs) levels, and total cholesterol which is the sum of HDL plus LDL and 20% of trigs.

Outcome measures

Measure	Mifepristone n=8 Participants Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Fasting Lipid Profile Trigs Baseline	107.88 mg/dL Standard Deviation 43.90
Fasting Lipid Profile Total Cholesterol Baseline	178.63 mg/dL Standard Deviation 31.35
Fasting Lipid Profile Total Cholesterol 6 months	171.43 mg/dL Standard Deviation 54.62
Fasting Lipid Profile LDL baseline	97.88 mg/dL Standard Deviation 22.34
Fasting Lipid Profile LDL 6 months	104.37 mg/dL Standard Deviation 44.69
Fasting Lipid Profile HDL Baseline	59.13 mg/dL Standard Deviation 19.50
Fasting Lipid Profile HDL 6 months	46.86 mg/dL Standard Deviation 14.26
Fasting Lipid Profile Trigs 6 months	100.29 mg/dL Standard Deviation 20.21

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: one participant had data missing at 6 months

Change in metabolic syndrome as assessed by weight

Outcome measures

Measure	Mifepristone n=8 Participants Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Weight Baseline	99.57 kg Standard Deviation 38.68
Weight 6 months	97.75 kg Standard Deviation 41.15

SECONDARY outcome

Timeframe: Baseline and 6 months

Change in Quality of Life - as assessed by the Cushing's Quality of Life questionnaire (CushingQoL). Patient completed questionnaire, 12 items, each scored on a 5 point score, resulting in a score of 12 (worst) to 60 (best) where higher scores indicate more favorable QOL.

Outcome measures

Measure	Mifepristone n=7 Participants Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
CushingQoL Baseline	37.2857 units on a scale Standard Deviation 9.86
CushingQoL 6 months	38.7857 units on a scale Standard Deviation 10.20

SECONDARY outcome

Timeframe: Baseline and 6 months

Change in Quality of Life as assessed by the Nottingham Health Profile (NHP) which is a patient reported questionnaire to measure a patient's view of their own health status. There are 6 sections (Energy level, Pain, Emotional Reaction, Sleep, Social Isolation, and Physical Abilities. All questions have only yes/no answer options and each section score is weighted so that the possible score range for any section is 0-100. The higher the score, the greater the number and severity of problems.

Outcome measures

Measure	Mifepristone n=7 Participants Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Nottingham Health Profile (NHP) Energy Level (EL) Baseline	32.60 units on a scale Interval 0.0 to 38.0
Nottingham Health Profile (NHP) EL 6 months	45.40 units on a scale Interval 18.0 to 72.4
Nottingham Health Profile (NHP) Pain (P) Baseline	24.88 units on a scale Interval 0.0 to 25.1
Nottingham Health Profile (NHP) P 6 months	32.08 units on a scale Interval 0.0 to 44.5
Nottingham Health Profile (NHP) Emotional Reaction (ER) Baseline	27.03 units on a scale Interval 0.0 to 38.7
Nottingham Health Profile (NHP) ER 6 months	35.09 units on a scale Interval 7.3 to 54.6
Nottingham Health Profile (NHP) Sleep (S) Baseline	24.87 units on a scale Interval 5.4 to 38.8
Nottingham Health Profile (NHP) S 6 months	31.15 units on a scale Interval 0.0 to 46.3
Nottingham Health Profile (NHP) Social Isolation (SI) Baseline	20.09 units on a scale Interval 0.0 to 21.0
Nottingham Health Profile (NHP) SI 6 months	31.15 units on a scale Interval 0.0 to 46.29
Nottingham Health Profile (NHP) Physical Abilities (PA) Baseline	23.06 units on a scale Interval 0.0 to 48.2
Nottingham Health Profile (NHP) PA 6 months	27.49 units on a scale Interval 17.6 to 42.2

SECONDARY outcome

Timeframe: Baseline and 6 months

Change in Quality of Life as assessed by the Hospital Anxiety and Depression Scale (HADS). Questionnaire with 7 items for anxiety and 7 items for depression, each item is scored on a 4 point response 0 - 3, with full range from 0 to 42, with higher score indicating more severe anxiety or depression

Outcome measures

Measure	Mifepristone n=7 Participants Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Hospital Anxiety and Depression Scale (HADS) Baseline	16.2857 units on a scale Standard Deviation 10.90
Hospital Anxiety and Depression Scale (HADS) 6 months	11.1667 units on a scale Standard Deviation 8.23

SECONDARY outcome

Timeframe: Baseline and 6 months

Change in Quality of Life as assessed by the Beck Depression Inventory. a 21-question multiple choice, self-report inventory that is used for measuring the severity of anxiety. Scoring is from a 0 (not at all) to 3 (severe) with a total score range of 0-63. Higher total scores indicate more severe anxiety symptoms.

Outcome measures

Measure	Mifepristone n=7 Participants Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Quality of Life Baseline	16.1429 units on a scale Standard Deviation 10.32
Quality of Life 6 months	11.7143 units on a scale Standard Deviation 11.70

SECONDARY outcome

Timeframe: Baseline and 6 months

Change in Quality of Life - as assessed by the State Trait Anxiety Inventory (STAI). The State-Trait Anxiety Inventory both state and trait anxiety separately. Each type of anxiety has its own scale of 20 different questions that are scored and averaged. Total scores range from 20 to 80, with higher scores correlating with greater anxiety.

Outcome measures

Measure	Mifepristone n=7 Participants Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
State Trait Anxiety Inventory (STAI) Baseline	25.4286 units on a scale Standard Deviation 17.61
State Trait Anxiety Inventory (STAI) 6 months	28.8571 units on a scale Standard Deviation 10.92

Adverse Events

Mifepristone

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Mifepristone n=8 participants at risk Mifepristone 300mg tablets taken once daily with dose increase of no more than 300mg once monthly and to a maximum dose of 1200mg daily as indicated by symptom response
Skin and subcutaneous tissue disorders Drug Rash	12.5% 1/8 • Number of events 1
Metabolism and nutrition disorders Hypokalemia	12.5% 1/8 • Number of events 1

Additional Information

Dr. Alice C. Levine

Ichan School of Medicine at Mount Sinai

Phone: 212-241-1500

Email: alice.levine@mountsinai.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place