Effects of Metyrapone in Patients With Endogenous Cushing's Syndrome

NCT02297945 | Completed Phase 3

• 1 other identifier: HRA112025-002
• Study Type: interventional
• Target: 50
• Locations: 8 countries
• Sites: 36

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.

Conditions

Cushing's Syndrome

Outcome Measures

Primary Outcomes (1)

• Normalization of cortisol levels (urinary free cortisol)

  3 months

Study Arms (1)

Metyrapone

EXPERIMENTAL

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.

Drug: metyrapone

Interventions

metyrapone DRUG

Single arm study

Also known as: Metopirone

Metyrapone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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

You may not qualify if:

• Pseudo Cushing's syndrome
• 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
• Advanced adrenocortical carcinoma or ectopic ACTH secretion (EAS) secondary to a small cell lung carcinoma
• Life expectancy less than 3 months
• Pituitary or adrenal surgery or pituitary irradiation or surgery of the ACTH-secreting ectopic tumor or bilateral adrenalectomy planned before the week 12 visit
• Pituitary irradiation within the previous 5 years (for Cushing's disease patients)
• 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
• Severe uncontrolled hypertension (\>180/110 mmHg) despite anti-hypertensive therapy (for otherwise eligible patients, blood pressure medication may be adjusted to meet this criterion)
• Severe hypokalemia (\< 2.5 mmol/L) despite corrective measures
• White blood cell counts \<3 x 109 /L; hemoglobin \<10 g/dL; platelets \<100 x 109 /L
• 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.

Sponsors & Collaborators

• HRA Pharma: lead

Study Sites (36)

University hospital Antwerp

Antwerp, Belgium

Location

CHU Erasme

Brussels, Belgium

Location

University hospital Saint Luc

Brussels, Belgium

Location

CHU Liège

Liège, Belgium

Location

Charité Berlin

Berlin, 10117, Germany

Location

Universitätsklinikum Essen

Essen, Germany

Location

Munich university

Munich, Germany

Location

University hospital Wuerzburg

Würzburg, Germany

Location

State health center

Budapest, 10062, Hungary

Location

Semmelweis Egyetem II. Belgyógyászati Klinika

Budapest, Hungary

Location

University Debrecen

Debrecen, Hungary

Location

University of Pecs

Pécs, Hungary

Location

University of Szeged

Szeged, Hungary

Location

San Luigi Gonzaga Hospital, University of Turin

Orbassano, Turin, 10043, Italy

Location

Grande Ospedale Metropolitano Niguarda

Milan, Italy

Location

Ospedale San Luca IRCCS Istituto Auxologico Italiano

Milan, Italy

Location

S. Giuseppe Hospital

Milan, Italy

Location

Federico II University

Naples, Italy

Location

University of Padova

Padua, Italy

Location

University of Turin

Turin, Italy

Location

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology

Gliwice, Poland

Location

University Hospital

Krakow, Poland

Location

University Clinical Hospital

Wroclaw, Poland

Location

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

Bucharest, Romania

Location

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

Bucharest, Romania

Location

Spitalul Universitar de Urgenta Militar Central 'Dr Carol Davila'

Bucharest, Romania

Location

Spitalul Clinic Judetean de Urgenta Cluj-Napoca

Cluj-Napoca, Romania

Location

S.C Centrul Clinic Mediquest SRL

Sângeorgiu de Mureş, Romania

Location

Spitalul Clinic Judetean de Urgenta Sibiu

Sibiu, Romania

Location

Spitalul Clinic Judetean Mures

Târgu Mureş, Romania

Location

University hospital clinic of Barcelona

Barcelona, Spain

Location

Hospital Universitario La Ribera

Valencia, Spain

Location

Ankara Numune Training and Research Hospital

Ankara, Turkey (Türkiye)

Location

Dokuz Eylul UMF

Izmir, Turkey (Türkiye)

Location

Ondokuz Mayıs University Medical Faculty

Samsun, Turkey (Türkiye)

Location

Karadeniz Teknik University

Trabzon, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Cushing Syndrome

Interventions

Metyrapone

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2014
• First Posted: November 21, 2014
• Study Start: April 1, 2015
• Primary Completion: November 1, 2019
• Study Completion: April 29, 2020
• Last Updated: September 25, 2020

Record last verified: 2020-09

Locations

IT (7); TU (4); HU (5); BE (4); RO (7); PL (3); DE (4); ES (2)