Effects of Metyrapone in Patients With Endogenous Cushing's Syndrome

Cushing's Syndrome Clinical Trial

— PROMPT  

Official title:

Prospective, Single Arm, Open-label, Multicenter, International Study to Assess the Effects of Metyrapone in Patients With Endogenous Cushing's Syndrome During a 12-week Treatment Period Followed by an Extension Period of 24 Weeks

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02297945
• Other study ID #: HRA112025-002
• Status: Completed
• Phase: Phase 3
• Start date: April 2015
• Est. completion date: April 29, 2020

Study information

• Verified date: September 2020
• Source: HRA Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: April 29, 2020
• Est. primary completion date: November 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cushing Syndrome
• Cushing's Syndrome
• Syndrome

Intervention

Drug:
• metyrapone
Single arm study

Locations

Country	Name	City	State
Belgium	University hospital Antwerp	Antwerp
Belgium	CHU Erasme	Brussels
Belgium	University hospital Saint Luc	Brussels
Belgium	CHU Liège	Liege
Germany	Charité Berlin	Berlin
Germany	Universitätsklinikum Essen	Essen
Germany	Munich university	Munich
Germany	University hospital Wuerzburg	Wuerzburg
Hungary	Semmelweis Egyetem II. Belgyógyászati Klinika	Budapest
Hungary	State health center	Budapest
Hungary	University Debrecen	Debrecen
Hungary	University of Pecs	Pecs
Hungary	University of Szeged	Szeged
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	San Luigi Gonzaga Hospital, University of Turin	Orbassano	Turin
Italy	University of Padova	Padova
Italy	University of Turin	Turin
Poland	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology	Gliwice
Poland	University Hospital	Krakow
Poland	University Clinical Hospital	Wroclaw
Romania	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 Mures
Romania	Spitalul Clinic Judetean de Urgenta Sibiu	Sibiu
Romania	Spitalul Clinic Judetean Mures	Târgu-Mures
Spain	University hospital clinic of Barcelona	Barcelona
Spain	Hospital Universitario La Ribera	Valencia
Turkey	Ankara Numune Training and Research Hospital	Ankara
Turkey	Dokuz Eylul UMF	Izmir
Turkey	Ondokuz Mayis University Medical Faculty	Samsun
Turkey	Karadeniz Teknik University	Trabzon

Sponsors (1)

Lead Sponsor	Collaborator
HRA Pharma

Countries where clinical trial is conducted

Belgium,  Germany,  Hungary,  Italy,  Poland,  Romania,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Normalization of cortisol levels (urinary free cortisol)		3 months