Back to resultsEffects of Metyrapone in Patients With Endogenous Cushing's Syndrome (PROMPT)
Primary Purpose
Cushing's Syndrome
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
metyrapone
Sponsored by
About this trial
This is an interventional treatment trial for 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:
- 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.
Sites / Locations
- University hospital Antwerp
- CHU Erasme
- University hospital Saint Luc
- CHU Liège
- Charité Berlin
- Universitätsklinikum Essen
- Munich university
- University hospital Wuerzburg
- State health center
- Semmelweis Egyetem II. Belgyógyászati Klinika
- University Debrecen
- University of Pecs
- University of Szeged
- San Luigi Gonzaga Hospital, University of Turin
- Grande Ospedale Metropolitano Niguarda
- Ospedale San Luca IRCCS Istituto Auxologico Italiano
- S. Giuseppe Hospital
- Federico II University
- University of Padova
- University of Turin
- Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
- University Hospital
- University Clinical Hospital
- Institutul National de Endocrinologie 'C.I Parhon' - Endocrinologie II
- Institutul National de Endocrinologie 'C.I Parhon' - Endocrinologie VI
- Spitalul Universitar de Urgenta Militar Central 'Dr Carol Davila'
- Spitalul Clinic Judetean de Urgenta Cluj-Napoca
- Spitalul Clinic Judetean de Urgenta Sibiu
- S.C Centrul Clinic Mediquest SRL
- Spitalul Clinic Judetean Mures
- University hospital clinic of Barcelona
- Hospital Universitario La Ribera
- Ankara Numune Training and Research Hospital
- Dokuz Eylul UMF
- Ondokuz Mayıs University Medical Faculty
- Karadeniz Teknik University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Metyrapone
Arm Description
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.
Outcomes
Primary Outcome Measures
Normalization of cortisol levels (urinary free cortisol)
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02297945
Brief Title
Effects of Metyrapone in Patients With Endogenous Cushing's Syndrome
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
April 2015 (Actual)
Primary Completion Date
November 2019 (Actual)
Study Completion Date
April 29, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
HRA Pharma
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cushing's Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Metyrapone
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
metyrapone
Other Intervention Name(s)
Metopirone
Intervention Description
Single arm study
Primary Outcome Measure Information:
Title
Normalization of cortisol levels (urinary free cortisol)
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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:
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.
Facility Information:
Facility Name
University hospital Antwerp
City
Antwerp
Country
Belgium
Facility Name
CHU Erasme
City
Brussels
Country
Belgium
Facility Name
University hospital Saint Luc
City
Brussels
Country
Belgium
Facility Name
CHU Liège
City
Liege
Country
Belgium
Facility Name
Charité Berlin
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Universitätsklinikum Essen
City
Essen
Country
Germany
Facility Name
Munich university
City
Munich
Country
Germany
Facility Name
University hospital Wuerzburg
City
Wuerzburg
Country
Germany
Facility Name
State health center
City
Budapest
ZIP/Postal Code
10062
Country
Hungary
Facility Name
Semmelweis Egyetem II. Belgyógyászati Klinika
City
Budapest
Country
Hungary
Facility Name
University Debrecen
City
Debrecen
Country
Hungary
Facility Name
University of Pecs
City
Pecs
Country
Hungary
Facility Name
University of Szeged
City
Szeged
Country
Hungary
Facility Name
San Luigi Gonzaga Hospital, University of Turin
City
Orbassano
State/Province
Turin
ZIP/Postal Code
10043
Country
Italy
Facility Name
Grande Ospedale Metropolitano Niguarda
City
Milan
Country
Italy
Facility Name
Ospedale San Luca IRCCS Istituto Auxologico Italiano
City
Milan
Country
Italy
Facility Name
S. Giuseppe Hospital
City
Milan
Country
Italy
Facility Name
Federico II University
City
Naples
Country
Italy
Facility Name
University of Padova
City
Padova
Country
Italy
Facility Name
University of Turin
City
Turin
Country
Italy
Facility Name
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
City
Gliwice
Country
Poland
Facility Name
University Hospital
City
Krakow
Country
Poland
Facility Name
University Clinical Hospital
City
Wrocław
Country
Poland
Facility Name
Institutul National de Endocrinologie 'C.I Parhon' - Endocrinologie II
City
Bucharest
Country
Romania
Facility Name
Institutul National de Endocrinologie 'C.I Parhon' - Endocrinologie VI
City
Bucharest
Country
Romania
Facility Name
Spitalul Universitar de Urgenta Militar Central 'Dr Carol Davila'
City
Bucharest
Country
Romania
Facility Name
Spitalul Clinic Judetean de Urgenta Cluj-Napoca
City
Cluj-Napoca
Country
Romania
Facility Name
Spitalul Clinic Judetean de Urgenta Sibiu
City
Sibiu
Country
Romania
Facility Name
S.C Centrul Clinic Mediquest SRL
City
Sângeorgiu De Mureş
Country
Romania
Facility Name
Spitalul Clinic Judetean Mures
City
Târgu-Mureş
Country
Romania
Facility Name
University hospital clinic of Barcelona
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario La Ribera
City
Valencia
Country
Spain
Facility Name
Ankara Numune Training and Research Hospital
City
Ankara
Country
Turkey
Facility Name
Dokuz Eylul UMF
City
Izmir
Country
Turkey
Facility Name
Ondokuz Mayıs University Medical Faculty
City
Samsun
Country
Turkey
Facility Name
Karadeniz Teknik University
City
Trabzon
Country
Turkey
12. IPD Sharing Statement
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Effects of Metyrapone in Patients With Endogenous Cushing's Syndrome
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