Effects of Metyrapone in Patients With Endogenous Cushing's Syndrome (PROMPT)

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

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.

Study Overview

• Status: Completed
• Conditions: Cushing's Syndrome
• Intervention / Treatment: Drug: metyrapone

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium
    • University Hospital Antwerp
  • Brussels, Belgium
    • CHU Erasme
  • Brussels, Belgium
    • University Hospital Saint Luc
  • Liege, Belgium
    • Chu Liege
• Germany
  • Berlin, Germany, 10117
    • Charite Berlin
  • Essen, Germany
    • Universitätsklinikum Essen
  • Munich, Germany
    • Munich university
  • Wuerzburg, Germany
    • University Hospital Wuerzburg
• Hungary
  • Budapest, Hungary, 10062
    • State Health Center
  • Budapest, Hungary
    • Semmelweis Egyetem II. Belgyógyászati Klinika
  • Debrecen, Hungary
    • University Debrecen
  • Pecs, Hungary
    • University of Pecs
  • Szeged, Hungary
    • University of Szeged
• Italy
  • Milan, Italy
    • Grande Ospedale Metropolitano Niguarda
  • Milan, Italy
    • Ospedale San Luca IRCCS Istituto Auxologico Italiano
  • Milan, Italy
    • S. Giuseppe Hospital
  • Naples, Italy
    • Federico II University
  • Padova, Italy
    • University of Padova
  • Turin, Italy
    • University of Turin
  • Turin
    • Orbassano, Turin, Italy, 10043
      • San Luigi Gonzaga Hospital, University of Turin
• Poland
  • Gliwice, Poland
    • Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
  • Krakow, Poland
    • University Hospital
  • Wrocław, Poland
    • University Clinical Hospital
• Romania
  • Bucharest, 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'
  • Cluj-Napoca, Romania
    • Spitalul Clinic Judetean de Urgenta Cluj-Napoca
  • Sibiu, Romania
    • Spitalul Clinic Judetean de Urgenta Sibiu
  • Sângeorgiu De Mureş, Romania
    • S.C Centrul Clinic Mediquest SRL
  • Târgu-Mureş, Romania
    • Spitalul Clinic Judetean Mures
• Spain
  • Barcelona, Spain
    • University Hospital Clinic of Barcelona
  • Valencia, Spain
    • Hospital Universitario La Ribera
• Turkey
  • Ankara, Turkey
    • Ankara Numune Training and Research Hospital
  • Izmir, Turkey
    • Dokuz Eylul UMF
  • Samsun, Turkey
    • Ondokuz Mayıs University Medical Faculty
  • Trabzon, Turkey
    • Karadeniz Teknik University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: metyrapone; Single arm study; Other Names: Metopirone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Normalization of cortisol levels (urinary free cortisol)	3 months

Collaborators and Investigators

• Sponsor: HRA Pharma

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): November 1, 2019
• Study Completion (Actual): April 29, 2020

Study Registration Dates

• First Submitted: November 19, 2014
• First Submitted That Met QC Criteria: November 19, 2014
• First Posted (Estimate): November 21, 2014

Study Record Updates

• Last Update Posted (Actual): September 25, 2020
• Last Update Submitted That Met QC Criteria: September 24, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Endocrine System Diseases; Disease; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Syndrome; Cushing Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Metyrapone
• Other Study ID Numbers: HRA112025-002