Study to assess the effects of metyrapone in patients with Cushing’s syndrome during a 12-week treatment period

Phase 1

• Conditions: Treatment of Cushing’s syndrome; MedDRA version: 20.0Level: PTClassification code 10011652Term: Cushing's syndromeSystem Organ Class: 10014698 - Endocrine disorders; Therapeutic area: Diseases [C] - Hormonal diseases [C19]

• Registration Number: EUCTR2014-000162-22-DE
• Lead Sponsor: aboratoire HRA Pharma

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-10-30
• Last Update Posted: 2 August 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

1. Any men and women = 18 years
2.Patients with endogenous Cushing’s syndrome for whom the following criteria apply:
•Newly diagnosed Cushing’s disease patients who are unsuitable for early surgery or wish to defer surgery;
•Or recurrent or persistent Cushing’s disease after pituitary surgery;
•Or patients with ectopic ACTH syndrome either occult or after surgery failure or inoperable or metastatic;
•Or patients with Cushing’s syndrome from adrenal causes who are unsuitable for early surgery or wish to defer surgery;
3.For patients receiving previous medical therapy, the following wash-out periods should be completed:
•Steroidogenesis inhibitors excluding mitotane (e.g. ketoconazole), 1 week
•Dopamine agonists (bromocriptine, cabergoline), 4 weeks
•Pasireotide S/C, 1 week
•Pasireotide LAR (formulated for once-monthly dosing), 12 weeks
•Mifepristone, 4 weeks
4.UFC = 1.5-fold ULN on each of the three 24-hour urinary sampling measurements (after previous treatment withdrawal if applicable or in non-treated patients) provided that the diagnosis of Cushing’s syndrome has been confirmed. Urine collections for UFC measurements will be done within 5 weeks before the baseline visit.
5.Female patients should not be at risk of pregnancy (could be included if sterilized, post-menopausal, sexually inactive or using methods of contraception throughout the study)
6.Able and willing to give voluntary, written informed consent to participate in the study
7.Agree to observe all study requirements and be available for all planned study visits

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 65
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

1.Pseudo Cushing’s syndrome
2.Cyclic Cushing’s syndrome defined by at least one normal UFC value among at least three 24-hour urinary sampling measurements over the previous 2 months
3.Advanced adrenocortical carcinoma or ectopic ACTH secretion (EAS) secondary to a small cell lung carcinoma
4. Life expectancy less than 3 months
5. Pituitary or adrenal surgery or pituitary irradiation or surgery of the ACTH-secreting ectopic tumor or bilateral adrenalectomy planned before the week 12 visit
6.Pituitary irradiation within the previous 5 years (for Cushing’s disease patients)
7. Enlarged pituitary adenoma (greater than 1 cm in vertical diameter and leaving less than 2 mm from the chiasma) or compression of the optic chiasma on the pituitary MRI for patients with Cushing’s disease
8. Severe uncontrolled hypertension (>180/110 mmHg) despite anti-hypertensive therapy (for otherwise eligible patients, blood pressure medication may be adjusted to meet this criterion)
9. Severe hypokalemia (< 2.5 mmol/L) despite corrective measures
10. White blood cell count <3 milliard /L; hemoglobin <10 g/dL; platelets <100 milliard/L
11. Any other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that in the judgment of the investigator, would present excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
12. Pregnant or positive pregnancy test at entrance or breast-feeding women
13. Current alcohol or drug abuse
14. Acute or chronic severe uncontrolled infections
15. Known hypersensitivity to metyrapone or to any of its excipients namely glycerol, disodium edentate, sodium hydroxide and phosphoric acid
16.Patients with mitotane (Lysodren®) plasma concentration > 3 mg/L
17.Participation in another treatment study or receiving any investigational treatment (drug, biological agent or device) within 30 days
18.Prohibited treatments

Study & Design

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