Compassionate Use of CORLUX® (Mifepristone) in the Treatment of Signs and Symptoms of Endogenous Cushing's Syndrome

• Sponsor: Corcept Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01371565
• Collaborator: (none)
• Enrollment: 4
• Locations: 5
• Arm: 1
• Duration (Months): 22
• Patients Per Site: 0.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a compassionate use study. In addition to providing compassionate use access to mifepristone, objectives of the study will be to evaluate the safety and utility of mifepristone in the treatment of the signs and symptoms of endogenous Cushing's syndrome when given on a compassionate use basis. The study will only enroll subjects whose physicians have determined that medical treatment is needed to control the symptoms or signs of hypercortisolemia.

Condition or Disease	Intervention/Treatment	Phase
Cushing's Disease; Cushing's Syndrome	Drug: Mifepristone	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Compassionate Use Protocol for the Administration of CORLUX® (Mifepristone) in the Treatment of the Signs and Symptoms of Endogenous Cushing's Syndrome
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: mifepristone	Drug: Mifepristone; mifepristone at doses from 300mg/day up to 1200mg/day; Other Names: CORLUX®

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events [6 months]

   Safety was assessed at all visits and adverse events were recorded.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Have a confirmed diagnosis of endogenous hypercortisolemia caused by ACTH dependent or

ACTH independent etiologies including:

• Cushing's Disease that (more than one may apply)

• has recurred after primary pituitary surgery

• has persisted despite pituitary surgery (failed pituitary surgery)

• has been treated with radiation therapy to the pituitary

• is not treatable with surgery

• exists in subjects who are not candidates for or who refuse surgery

• Ectopic ACTH

• Ectopic CRF secretion

• Adrenal adenoma

• Adrenal carcinoma

• Adrenal autonomy

1. Have documented biochemical evidence of endogenous hypercortisolemia which includes elevated urinary free cortisol.

2. Require medical treatment of hypercortisolemia.

Exclusion Criteria:

Individuals not eligible to be enrolled into the study are those who:

• Have de novo Cushing's disease and are surgical candidates for pituitary surgery.

• Have an acute or unstable medical problem, which could be aggravated by mifepristone treatment.

• Taking medications within 14 days of the baseline visit (Day 1) that a) have a large first pass metabolism largely mediated by CYP3A4 and a narrow therapeutic margin and/or b) are strong CYP3A4 inhibitors.

• Female patients of reproductive potential, who are pregnant or who are unable or unwilling to use medically acceptable, non-hormonal methods of contraception during the study.

• Have received investigational treatment (drug, biological agent or device) within 30 days of Screening

• Have a history of an allergic reaction or intolerance to CORLUX (mifepristone)

• Have a non-endogenous source of hypercortisolemia such as factious hypercortisolemia (exogenous source of glucocorticoid, iatrogenic Cushing's syndrome), factious or therapeutic use of ACTH

• Have Pseudo-Cushing's syndrome.

• Postmenopausal women with an intact uterus who have experienced unexplained vaginal bleeding within 12 months of Screening are excluded.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Center for Diabetes and Endocrine Care	Hollywood	Florida	United States	33021
2	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
3	University of Michigan Medical Center	Ann Arbor	Michigan	United States	48109
4	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
5	The Ohio State University, Division of Endocrinology Diabetes and Metabolism	Columbus	Ohio	United States	43210

Sponsors and Collaborators

• Corcept Therapeutics

Investigators

• Study Director: Coleman Gross, M.D., Corcept Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Corcept Therapeutics
• ClinicalTrials.gov Identifier: NCT01371565
• Other Study ID Numbers: C1073-405
• First Posted: Jun 13, 2011
• Last Update Posted: Mar 18, 2014
• Last Verified: Feb 1, 2014

• Keywords provided by Corcept Therapeutics: Cushing's Disease; Cushing's Syndrome; Cushings; Pituitary; Ectopic ACTH secretion
• Additional relevant MeSH terms: ACTH-Secreting Pituitary Adenoma; Pituitary ACTH Hypersecretion; Cushing Syndrome; Syndrome; Mifepristone

Study Results

Participant Flow

Recruitment Details	Eligible patients were men or non-pregnant women 18 yrs or older requiring medical treatment for symptoms of endogenous Cushing's syndrome due to ectopic ACTH, adrenal tumors/adrenal hyperplasia, or Cushing's disease if not candidates for pituitary surgery. Pts w/de novo Cushing's disease who were candidates for surgery were not enrolled.
Pre-assignment Detail	All patients received active drug (no placebo).

Arm/Group Title	Mifepristone
Arm/Group Description	At doses from 300mg/day up to 1200mg/day
Period Title: Overall Study
STARTED	4
COMPLETED	1
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Mifepristone
Arm/Group Description	At doses from 300mg/day up to 1200mg/day
Overall Participants	4
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	3 75%
>=65 years	1 25%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.8 (17.9)
Sex: Female, Male (Count of Participants)
Female	1 25%
Male	3 75%
Region of Enrollment (participants) [Number]
United States	4 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events
Description	Safety was assessed at all visits and adverse events were recorded.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Due to the small number of patients enrolled (N=4), no formal assessments were planned. All patients who received study drug were included in the safety review.

Arm/Group Title	Mifepristone
Arm/Group Description	At doses from 300mg/day up to 1200mg/day
Measure Participants	4
Number [participants]	4 100%

Adverse Events

Time Frame	From date of consent to final visit.
Adverse Event Reporting Description	All patients who received at least one dose of study drug are included.
Arm/Group Title	Mifepristone
Arm/Group Description	At doses from 300mg/day up to 1200mg/day
All Cause Mortality
	Mifepristone
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Mifepristone
	Affected / at Risk (%)	# Events
Total	1/4 (25%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adrenal carcinoma	1/4 (25%)	1
Psychiatric disorders
Mental status changes	1/4 (25%)	2
Renal and urinary disorders
Haematuria	1/4 (25%)	1
Other (Not Including Serious) Adverse Events
	Mifepristone
	Affected / at Risk (%)	# Events
Total	4/4 (100%)
Blood and lymphatic system disorders
Pancytopenia	1/4 (25%)	1
Eye disorders
Eye irritation	1/4 (25%)	1
Gastrointestinal disorders
Dysphagia	1/4 (25%)	1
Dyspepsia	1/4 (25%)	1
Vomiting	1/4 (25%)	1
General disorders
Influenza like illness	1/4 (25%)	1
Swelling	1/4 (25%)	1
Thirst	1/4 (25%)	1
Asthenia	1/4 (25%)	1
Fatigue	1/4 (25%)	1
Hepatobiliary disorders
Gallbladder polyp	1/4 (25%)	1
Infections and infestations
Influenza	1/4 (25%)	1
Upper respiratory tract infection	1/4 (25%)	1
Investigations
Blood potassium decreased	2/4 (50%)	2
Blood potassium increased	1/4 (25%)	1
Metabolism and nutrition disorders
Hypoglycaemia	2/4 (50%)	2
Decreased appetite	1/4 (25%)	1
Food craving	1/4 (25%)	1
Metabolic alkalosis	1/4 (25%)	1
Musculoskeletal and connective tissue disorders
Arthropathy	1/4 (25%)	2
Back pain	1/4 (25%)	1
Muscle twitching	1/4 (25%)	1
Pain in extremity	1/4 (25%)	1
Nervous system disorders
Dysarthria	1/4 (25%)	1
Headache	1/4 (25%)	2
Hypoaesthesia	1/4 (25%)	1
Restless legs syndrome	1/4 (25%)	1
Restless	1/4 (25%)	1
Somnolence	1/4 (25%)	1
Psychiatric disorders
Anxiety	1/4 (25%)	1
Insomnia	1/4 (25%)	1
Renal and urinary disorders
Haematuria	1/4 (25%)	1
Nocturia	1/4 (25%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/4 (25%)	1
Cough	1/4 (25%)	1
Pleural effusion	1/4 (25%)	1
Pneumonia aspiration	1/4 (25%)	1
Skin and subcutaneous tissue disorders
Alopecia	1/4 (25%)	1
Drug eruption	1/4 (25%)	1
Skin erosion	1/4 (25%)	1
Vascular disorders
Epistaxis	1/4 (25%)	1
Haemorrhage	1/4 (25%)	1
Hypertension	1/4 (25%)	1
Hypotension	1/4 (25%)	2
Jugular vein thrombosis	1/4 (25%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.