Clinical trial NCT02297945: Effects of Metyrapone in Patients With Endogenous Cushing's Syndrome
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cushing's Syndrome
Lead sponsor: HRA Pharma
Sponsor class: INDUSTRY
First posted: 2014-11-21
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Normalization of cortisol levels (urinary free cortisol)
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: University hospital Antwerp
city: Brussels
country: Belgium
facility: CHU Erasme
city: Brussels
country: Belgium
facility: University hospital Saint Luc
city: Liege
country: Belgium
facility: CHU Liège
city: Berlin
country: Germany
facility: Charité Berlin
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Munich
country: Germany
facility: Munich university
city: Wuerzburg
country: Germany
facility: University hospital Wuerzburg
city: Budapest
country: Hungary
facility: State health center
city: Budapest
country: Hungary
facility: Semmelweis Egyetem II. Belgyógyászati Klinika
city: Debrecen
country: Hungary
facility: University Debrecen
city: Pecs
country: Hungary
facility: University of Pecs
city: Szeged
country: Hungary
facility: University of Szeged
city: Orbassano
country: Italy
facility: San Luigi Gonzaga Hospital, University of Turin
state: Turin
city: Milan
country: Italy
facility: Grande Ospedale Metropolitano Niguarda
city: Milan
country: Italy
facility: Ospedale San Luca IRCCS Istituto Auxologico Italiano
city: Milan
country: Italy
facility: S. Giuseppe Hospital
city: Naples
country: Italy
facility: Federico II University
city: Padova
country: Italy
facility: University of Padova
city: Turin
country: Italy
facility: University of Turin
city: Gliwice
country: Poland
facility: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
city: Krakow
country: Poland
facility: University Hospital
city: Wrocław
country: Poland
facility: University Clinical Hospital
city: Bucharest
country: Romania
facility: Institutul National de Endocrinologie 'C.I Parhon' - Endocrinologie II
city: Bucharest
country: Romania
facility: Institutul National de Endocrinologie 'C.I Parhon' - Endocrinologie VI
city: Bucharest
country: Romania
facility: Spitalul Universitar de Urgenta Militar Central 'Dr Carol Davila'
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Cluj-Napoca
city: Sibiu
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Sibiu
city: Sângeorgiu De Mureş
country: Romania
facility: S.C Centrul Clinic Mediquest SRL
city: Târgu-Mureş
country: Romania
facility: Spitalul Clinic Judetean Mures
city: Barcelona
country: Spain
facility: University hospital clinic of Barcelona
city: Valencia
country: Spain
facility: Hospital Universitario La Ribera
city: Ankara
country: Turkey
facility: Ankara Numune Training and Research Hospital
city: Izmir
country: Turkey
facility: Dokuz Eylul UMF
city: Samsun
country: Turkey
facility: Ondokuz Mayıs University Medical Faculty
city: Trabzon
country: Turkey
facility: Karadeniz Teknik University
Study officials:
References: