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: 14.0Level: PTClassification code 10011652Term: Cushing's syndromeSystem Organ Class: 10014698 - Endocrine disorders; MedDRA version: 14.0Level: PTClassification code 10014146Term: Ectopic ACTH syndromeSystem Organ Class: 10014698 - Endocrine disorders; Therapeutic area: Diseases [C] - Hormonal diseases [C19]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-10-09
• Last Update Posted: 5 August 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 35

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. Glycemic disorder that is considered to be caused or worsened by the hypercortisolism.
Glycemic disorders will be defined and categorized at pre-inclusion as follows:
oKnown diabetes defined by
?fasting plasma glucose level = 7.0 mmol/l (126 mg/dL)
? or treated diabetes. In addition, treatment should be stable, i.e.
-for thiazolidinediones, patients must have been on stable therapy for at least four months prior to study entry
-for all other diabetes treatments, patients must have been on stable therapy for at least two weeks prior to study entry, for insulin the dose should be stable as long as possible before study entry
oDiabetes diagnosed at pre-inclusion visit and defined by:
?2-hour glucose plasma level after 75 g OGTT = 11.1 mmol/L (200 mg/dL)
oImpaired Glucose Tolerance (IGT) defined at pre-inclusion visit by:
?2-hour glucose plasma level after 75 g OGTT = 7.8 mmol/L (140 mg/dL) and < 11 mmol/L (200 mg/dL)
oImpaired Fasting Glucose (IFG) defined at pre-inclusion visit by:
?fasting plasma glucose level = 5.5 mmol/L (100 mg/dL) and < 7 mmol/L (126 mg/dL)
AND
3. At least one of the following clinical symptoms attributable to the Cushing’s syndrome:
oIncreased weight gain = 5% within 1 year
oOverweight defined by BMI > 25 kg/m2
oTruncal obesity defined by waist circumference = 94 cm for men or = 80 cm for women (IDF definition) and/or documented by truncal fat mass at DEXA scan
oDepression (treated or not) defined by a BDI-II score > 1
oProximal muscle weakness as assessed by straight leg lift clinical test < 120 sec
oBruising evaluated at clinical examination and with photos if possible
oViolaceous striae evaluated at clinical examination and with photos if possible
oFacial plethora evaluated at clinical examination and with photos if possible
oDorsocervical fat pad evaluated at clinical examination and with photos if possible

In addition, the following criteria should be met:
-Written informed consent to participate in the study (including taking photos)
-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 85 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 any measurement of Urinary Free Cortisol over the previous 2 months < 2 times the upper normal limit
-Children (age less than 18) and patients over 85 years
-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 two months
-Surgery planned within 8 weeks after inclusion, especially bilateral adrenalectomy
-Uncontrolled diabetes (plasma glucose > 15.0 mmol/ (270 mg/dL) and/or HbA1c > 10%)
-Uncontrolled hypertension (blood pressure > 180/110 mmHg)
-Recent (less than two weeks prior to inclusion) initiation of corrective treatments for 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)
-Severe hypokalemia (plasma K < 3.0 mm/L).
-Uncontrolled severe active infection
-In women, known endometrial cancer, history of endometrial hyperplasia or vaginal bleeding of unknown cause
-Premenopausal women with hemorrhagic disorders or on anticoagulants
-Recent (less than two weeks prior to inclusion) initiation of or significant change in dose of anti-tumor therapy
-Previous treatment with approved or experimental steroidogenesis inhibitors, somatostatin analogues within one week of admission (eight weeks for patients on octreotide LAR or on lanreotide autogel).
-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
-Inherited porphyria
-Positive pregnancy test at inclusion
-Use of antiretroviral agents, midazolam, cabergoline, erythromycin, or grapefruit juice within two weeks of the study

Study & Design

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