Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ongoing, recruiting
Participants planned
50
Countries
1
Sites
3
patients with adrenal incidentalomas and subclinical/mild Cushing’s syndrome
The main aim of the study is to investigate the efficacy of adding Metyrapone to the standard antihypertensive treatment in improving blood pressure control of hypertensive patients with SCS and bilateral adrenal tumors
Key facts
- Sponsor
- Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Hormonal diseases [C19]
- Trial duration
- 22 Sep 2020 → ongoing
- Decision date (initial)
- 2024-11-27
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Ministero della Salute-BANDO RICERCA FINALIZZATA 2018-GR-2018-12365398 · IRCCS AUOBO Policlinico di S.Orsola
External identifiers
- EU CT number
- 2024-518932-34-00
- EudraCT number
- 2019-002008-41
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy
The main aim of the study is to investigate the efficacy of adding Metyrapone to the standard antihypertensive treatment in improving blood pressure control of hypertensive patients with SCS and bilateral adrenal tumors
Secondary objectives 1
- - to identify biomarkers of treatment efficacy and monitoring - to evaluate the adrenal morphology after treatment with Metyrapone
Conditions and MedDRA coding
patients with adrenal incidentalomas and subclinical/mild Cushing’s syndrome
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | SOC | 10014698 | Endocrine disorders | 5 |
Study design 2 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Run in During run-in, patients will receive a standardized antihypertensive treatment, following the current European guidelines. Patients will be evaluated monthly to check blood pressure and identify the minimum effective dose of antihypertensive drug, to keep blood pressure <130/85 mmHg. Blood pressure will be measured during medical evaluation. Home monitoring and 24-hours profile blood pressure, together with complete cardiovascular and metabolic profile assessment will be performed
|
Not Applicable | None | standardized antihypertensive treatment: During run-in, patients will receive a standardized antihypertensive treatment, following the current European guidelines | |
| 2 | Randomization During the intervention period, patients receiving Metyrapone (Group A) will be evaluated weekly to titrate the dose of the drug to the maximum tolerated dose, not exceeding 750 mg die, according to cortisol and cortisone levels. Electrolytes will be monitored, and potential side effects will be investigated. Patients receiving Metyrapone (Group A), who achieved the maximum tolerated dose, and patients not receiving Metyrapone (Group B) will undergo ambulatory and home monitoring blood pressure check at monthly intervals, to optimize antihypertensive treatment and keep blood pressure >100/60 mmHg and <130/85 mmHg. At each evaluation, a complete clinical evaluation will be performed, and blood and saliva samples will be taken to assess the steroid profile by liquid-chromatography tandem mass spectrometry (LC-MS/MS). At the end of the study, cardiovascular and metabolic profiles will be re-assessed, and an abdominal CT scan will be repeated
|
Randomised Controlled | None | Group A: Patients receiving Metyrapone Group B: Patients not receiving Metyrapone |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- Run-in Inclusion criteria for run-in phase: - age >18 years and <75 years - monolateral/bilateral nodules with benign radiological characteristics associated with enlarged adrenal limb width >5 mm at CT scan - SCS (absence of catabolic signs of Cushing’s syndrome) associated with at least one of the following conditions: o Cortisol after 1 mg dexamethasone suppression test >50 nmol/L and baseline ACTH <10 pg/mL o Cortisol after 1 mg dexamethasone suppression test >50 nmol/L and high salivary cortisol at 11 p.m. o Cortisol after 1 mg dexamethasone suppression test >138 nmol/L - Arterial hypertension (blood pressure =140/90 mmHg and/or current treatment with antihypertensive drugs) - Patients who are not candidate for adrenalectomy- Inclusion criteria-randomization (phase 2) - BP >100/60 mmHg and <130/85 mmHg undergoing antihypertensive therapy (lowest effective dose effective dose) within 6-10 months after enrollment-Written informed consent
Exclusion criteria 1
- Body mass index =40 kg/m2 - Pregnancy or breastfeeding - Women in childbearing age who do not use barrier contraceptives. Barrier contraceptives are: o male or female condom with or without spermicide o cap, diaphragm or sponge with spermicide o a combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods) - Glucocorticoid treatment during the last year before enrollment - Drugs known to have interactions with Metyrapone - Drug allergy to Metyrapone or drugs belonging to the same class - Patients with severe illness - Patients with primary adrenal insufficiency and severe hypopituitarism - Patients with reduced liver function - Patients with untreated hypothyroidism or taking drugs acting on the hypothalamuspituitary-adrenal axis - Patients with drug hypersensitivity to Metyrapone or to one of the excipients listed in paragraph 6.1 of the summary of product characteristics (SPCs) – Metyrapone.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary endpoint of the study is the reduction of the number and/or the dose of antihypertensive drugs after 12 months of treatment with Metyrapone, while keeping blood pressure within pre-fixed target range (>100/60 mmHg e <130/85 mmHg)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD7941729 · Product
- Active substance
- Metyrapone
- Pharmaceutical form
- CAPSULE, SOFT
- Route of administration
- ORAL
- Max daily dose
- 750 mg milligram(s)
- Max total dose
- 268.50 g gram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- V04CD01 — METYRAPONE
- Marketing authorisation
- 043094010
- MA holder
- HRA PHARMA RARE DISEASES
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
- Sponsor organisation
- Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
- Address
- Via Pietro Albertoni 15
- City
- Bologna
- Postcode
- 40138
- Country
- Italy
Scientific contact point
- Organisation
- Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
- Contact name
- Guido Di Dalmazi
Public contact point
- Organisation
- Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
- Contact name
- Barbara Lotito
Third parties 2
| Organisation | City, country | Duties |
|---|---|---|
| Fullcro S.r.l. ORG-100053075
|
Rome, Italy | On site monitoring, Other, Data management, E-data capture |
| Clinical Research Technology S.r.l. ORG-100027504
|
Salerno, Italy | Code 8 |
Locations
1 EU/EEA country · 3 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruiting | 50 | 3 |
| Rest of world | — | 0 | — |
Investigational sites
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
MED.CHIR.MALATTIE DIGESTIVE,EPATICHE ENDOCRINO-METABOLICHE,Endocrinologia,prevenzione,cura diabete, Via Pietro Albertoni 15, 40138, Bologna
Azienda Ospedaliera Universitaria Federico II Di Napoli
Dipartimento di Medicina Clinica e Chirurgica, Sezione di Endocrinologia, Via Sergio Pansini 5, 80131, Naples
Azienda Ospedaliera di Padova
Endocrinologia, via Ospedale Civile 105, Via Nicolo' Giustiniani 2, 35128, Padova
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2020-09-22 | 2021-02-23 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 10 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2024-518932-34-00_FP | 1.2 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_placeholder_FP | N.A. |
| Subject information and informed consent form (for publication) | L1_GP LETTER_FP | 1.1 |
| Subject information and informed consent form (for publication) | L1_ICF_data protection_FP | 1.0 |
| Subject information and informed consent form (for publication) | L1_ICF_participation_FP | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS_data protection_FP | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS_participation_FP | 1.1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_METIRAPONE_FP | N.A. |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_EN_2024-518932-34-00_FP | 1.2 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_IT_2024-518932-34-00_FP | 1.2 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-14 | Italy | Acceptable 2024-11-12
|
2024-11-27 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-02-20 | Italy | Acceptable 2024-11-12
|
2025-02-20 |