Effects of Metyrapone in Patients With Endogenous Cushing's Syndrome

NCT ID: NCT02297945

Last Updated: 2020-09-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2020-04-29

Brief Summary

The purpose of this prospective, international phase III/IV study is to assess the efficacy and safety of metyrapone in patients with endogenous Cushing's syndrome during up to 36 weeks of treatment. The ability of metyrapone (250 mg capsules) to normalize urinary free cortisol (UFC) levels will be assessed during up to 36 weeks (9 months) of treatment.

Detailed Description

This study will include Cushing disease patients with persistent or recurrent disease (after pituitary surgery) or who are newly diagnosed but are unsuitable for early surgery or wish to defer surgery. It will also include patients with ectopic ACTH syndrome (either occult, after surgery failure, or inoperable or metastatic) and patients with Cushing's syndrome from adrenal causes.

The ability of metyrapone to normalize urinary free cortisol levels will be assessed during up to 36 weeks (9 months) of treatment. Patients participating in this study and who are controlled or close to the target at the end of a 3-months period may continue with an optional extension period of 6 months in which the long-term efficacy and safety profiles of metyrapone will be assessed. This extension study is intended to provide new findings to consolidate existing efficacy and safety data on metyrapone in the treatment of Cushing's syndrome.

Conditions

Cushing's Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Metyrapone

Metyrapone will be administered orally in an open-label fashion. Two possible initiation doses will be used depending on the severity of hypercortisolism, dose will then be adjusted (up or down-titrated) during the first month on an individual basis according to clinical tolerance and cortisol levels achieved.

Group Type: EXPERIMENTAL

metyrapone

Intervention Type: DRUG

Single arm study

Interventions

metyrapone

Single arm study

Intervention Type: DRUG

Other Intervention Names

Metopirone

Eligibility Criteria

Inclusion Criteria

1. Patients with endogenous Cushing's syndrome:

• Cushing disease patients with persistent or recurrent disease (after pituitary surgery) or who are newly diagnosed but are unsuitable for early surgery or wish to defer surgery;
• Patients with ectopic ACTH syndrome (either occult, after surgery failure, or inoperable or metastatic);
• Patients with Cushing's syndrome from adrenal causes

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 counts <3 x 109 /L; hemoglobin <10 g/dL; platelets <100 x 109 /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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

HRA Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University hospital Antwerp

Antwerp, , Belgium

CHU Erasme

Brussels, , Belgium

University hospital Saint Luc

Brussels, , Belgium

CHU Liège

Liège, , Belgium

Charité Berlin

Berlin, , Germany

Universitätsklinikum Essen

Essen, , Germany

Munich university

Munich, , Germany

University hospital Wuerzburg

Würzburg, , Germany

State health center

Budapest, , Hungary

Semmelweis Egyetem II. Belgyógyászati Klinika

Budapest, , Hungary

University Debrecen

Debrecen, , Hungary

University of Pecs

Pécs, , Hungary

University of Szeged

Szeged, , Hungary

San Luigi Gonzaga Hospital, University of Turin

Orbassano, Turin, Italy

Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Ospedale San Luca IRCCS Istituto Auxologico Italiano

Milan, , Italy

S. Giuseppe Hospital

Milan, , Italy

Federico II University

Naples, , Italy

University of Padova

Padua, , Italy

University of Turin

Turin, , Italy

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology

Gliwice, , Poland

University Hospital

Krakow, , Poland

University Clinical Hospital

Wroclaw, , Poland

Institutul National de Endocrinologie 'C.I Parhon' - Endocrinologie II

Bucharest, , Romania

Institutul National de Endocrinologie 'C.I Parhon' - Endocrinologie VI

Bucharest, , Romania

Spitalul Universitar de Urgenta Militar Central 'Dr Carol Davila'

Bucharest, , Romania

Spitalul Clinic Judetean de Urgenta Cluj-Napoca

Cluj-Napoca, , Romania

S.C Centrul Clinic Mediquest SRL

Sângeorgiu de Mureş, , Romania

Spitalul Clinic Judetean de Urgenta Sibiu

Sibiu, , Romania

Spitalul Clinic Judetean Mures

Târgu Mureş, , Romania

University hospital clinic of Barcelona

Barcelona, , Spain

Hospital Universitario La Ribera

Valencia, , Spain

Ankara Numune Training and Research Hospital

Ankara, , Turkey (Türkiye)

Dokuz Eylul UMF

Izmir, , Turkey (Türkiye)

Ondokuz Mayıs University Medical Faculty

Samsun, , Turkey (Türkiye)

Karadeniz Teknik University

Trabzon, , Turkey (Türkiye)

Countries

Belgium; Germany; Hungary; Italy; Poland; Romania; Spain; Turkey (Türkiye)

Other Identifiers

HRA112025-002

Identifier Type: -

Identifier Source: org_study_id