Prospective, open-label, multicenter, international study of mifepristone for symptomatic treatment of Cushing's syndrome caused by ectopic Adrenal Corticotrophin Hormone (ACTH) secretion. - HRA052015 in EAS

• Conditions: Treatment of Cushing's syndrome caused by ectopic Adrenal Corticotrophin Hormone (ACTH) secretion.; MedDRA version: 8.1Level: LLTClassification code 10014155Term: Ectopic corticotrophin syndrome

• Registration Number: EUCTR2006-004679-36-NL
• Lead Sponsor: aboratoire HRA Pharma

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-01-31
• Last Update Posted: 29 May 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

Subjects will be included if they have ALL of the three following criteria:

1. Hypercortisolism from Cushing’s syndrome caused by ectopic ACTH secretion confirmed by:
- Inferior petrosal sinus sampling (IPSS) with a central to peripheral ACTH ratio of less than 2.0 before CRH administration and less than 3.0 after CRH administration.
- or biopsy with ACTH immunoreactivity.
- or presence of a tumor evidenced by imaging combined with both a negative CRH test and a negative 8 mg dexamethasone suppression test.
No major change in tumor status/anti-tumor therapy should be expected during the study

AND
2. Glucose intolerance AND/OR hypertension that is considered to be caused or worsened by the hypercortisolism:
oDiabetes defined by
?fasting plasma glucose level = 7.0 mmol/l (126 mg/dl)
? or 2-hour glucose plasma level after 75 g OGTT = 11.1 mmol/l (200 mg/dl)
?or treated diabetes
or glucose intolerance defined by:
?fasting plasma glucose values between 5.5 mmol/l (100 mg/dl) and 7.0 mmol/l (126 mg/dl) or 2-hour glucose plasma level after 75 g OGTT = 7.8 mmol/l (140 mg/dl) ) and < 11.1 mmol/l (200 mg/dl)
?Prior to study entry, fasting blood sugar must be less than 11.1 mmol/l (200 mg/dl) for at least two weeks
oHypertension defined by
?systolic BP = 140 mm Hg and/or diastolic BP = 90 mm Hg
?Prior to study entry, BP must be less than 180/110 mmHg for at least two weeks
?or treated hypertension

AND
3. At least one of the following symptoms attributable to the Cushing’s syndrome:
oBody weight increase or truncal obesity
oDepression or treated depression or psychiatric disorder
oFatigue
oProximal muscle weakness
o Hirsutism
o Hypokalemia
o Bruising
o Violaceous striae
o In men, gynecomastia or libido decrease
o Impaired cognition or memory
oHyperpigmentation
oAmenorrhea
oOsteopenia or osteoporosis

In addition, the following criteria should be met:
-Written informed consent to participate in the study
-Female subjects should be sterilized, post-menopausal, sexually inactive or willing to use barrier methods of contraception throughout the study.
-Subject willing to return to investigational site during the full course of the study
-Age in the range of 18 to 75 years inclusive
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Evidence for Cushing’s disease as judged by positive inferior petrosal sinus sampling or a lesion on pituitary MRI with positive CRH test
- Suspected or known adrenocortical cancer or adenomas, as judged by ACTH values < 10 pg/ml and adrenal mass
- Subjects with cyclic Cushing’s syndrome defined by at least 3 measurements of Urinary Free Cortisol over the previous two months without normal values.
- Children (age less than 18) and subject of more than 75 years of age
- Pregnant or lactating women. A urinary pregnancy test will be performed in women of childbearing potential unless they have a history of menopause prior to Cushing’s syndrome or hysterectomy
- Life expectancy less than three months
- Severe uncontrolled diabetes
- Grade III or IV hypertension
- Recent (less than two weeks prior to inclusion) initiation of corrective treatments for diabetes, hypertension or depression
- Clinically significantly impaired cardiovascular function (e.g. stage IV cardiac failure)
- Severe liver disease (liver enzymes = 3 x the institutional upper limit of normal range)
- Severe renal impairment (serum creatinine = 2.2 mg/dl or creatinine clearance < 30 ml/min)
- Uncontrolled severe active infection
- In women, known endometrial cancer, history of endometrial hyperplasia or vaginal bleeding of unknown cause
- Recent (less than two weeks prior to inclusion) initiation of or significant change in dose of anti-tumor therapy
- Treatment with approved or experimental steroidogenesis inhibitors, adrenolytic agents or somatostatin analogues within four weeks of admission
- Plasma mitotane concentration > 5 µg/ml
- Impaired mental capacity or markedly abnormal psychiatric evaluation that precludes informed consent
- Body weight over 136 kg, which is the limit for the tables used in the scanning areas

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified