Treatment of Cushing’s syndrome MedDRA version: 20.0 Level: PT Classification code 10011652 Term: Cushing's syndrome System Organ Class: 10014698 - Endocrine disorders
Conditions
Interventions
Trade Name: Metopirone 250 mg capsules
Product Name: metyrapone
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: METYRAPONE
CAS Number: 54-36-4
Concentration unit: mg milligram(s)
Concentration
Sponsors
Laboratoire HRA Pharma
Eligibility
Sex/Gender
All
Inclusion criteria
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
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 ( 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess the efficacy of metyrapone (MTP) to normalize cortisol levels (Urinary Free Cortisol – UFC) after 12 weeks of treatment in patients with endogenous Cushing’s syndrome (CS).;Secondary Objective: A)To assess the effects of metyrapone after 12 weeks of treatment on: 1)Salivary and serum cortisol levels 2)Hormonal and biochemical parameters that are associated with Cushing’s syndrome or represent safety measurements 3)Clinical signs of Cushing’s syndrome 4)Quality of life as judged by Cushing’s Quality of Life (CushingQoL) questionnaire and Tuebingen Cushing's disease quality of life inventory 5)Safety and tolerability B)To identify factors that predict the success rate defined as eucortisolemia achievement at 12 weeks. Parameters for identifying these factors will include age, gender, mean baseline UFC and cause of CS. C) To assess the effects of long-term MTP treatment on efficacy and safety parameters (up to 36 weeks of treatment) ;Primary end point(s): mean 24-hour UFC;Timepoint(s) of evaluation of this end point: after 12 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Morning serum cortisol (except for women taking an estrogen-containing oral contraceptive), salivary cortisol day curve, laboratory tests (fasting glucose, fasting insulin levels, Oral Glucose Tolerance Test (OGTT), Insulin Sensitivity Index (ISI), HbA1c, lipids, blood pressure, clinical signs of Cushing’s syndrome and the results of the quality of life questionnaires. The dosage of treatments for hypertension, diabetes and hypokalemia will be recorded and assessed for efficacy evaluation.;Timepoint(s) of evaluation of this end point: after 36 weeks of treatment | — |
Countries
Belgium, Germany, Hungary, Italy, Poland, Romania, Spain, Turkey
Contacts
Public ContactAna
Laboratoire HRA Pharma
Outcome results
None listed