Efficacy and safety of osilodrostat with drug combination in patients with hypertension caused by Cushing’s syndrome

3 1 1

What is this study about?

The study looks at people with Cushing’s syndrome, a rare condition where the body makes too much cortisol, a hormone that can cause high blood pressure (hypertension) and other problems. The excess cortisol, called hypercortisolaemia, is the main reason for the blood‑pressure issues. Participants will receive either the medication osilodrostat, which blocks cortisol production, or an inactive tablet (placebo) that looks the same.

The main goal is to see if the drug can bring the level of cortisol measured in urine back to normal. The trial is double‑blind, meaning neither the participants nor the doctors know who gets the real medicine, and it lasts about 30 weeks. People are randomly assigned to one of the two groups and take a tablet each day.

During the study, participants will provide urine samples to measure urinary‑free cortisol, have their blood pressure checked regularly, and may undergo a sugar‑drink test (OGTT) to look at how their body handles glucose. These checks help researchers understand how well the treatment works and whether any side effects appear. The study involves several clinic visits, simple tests, and daily medication taken at home.

1 randomisation and first dose

after joining the study you are assigned, in a double‑blind manner, to receive either osilodrostat tablets or matching placebo tablets. the assignment is unknown to you and to the study staff.

the first tablet is taken on the same day as the randomisation.

2 baseline assessments

a set of measurements is performed before the daily medication starts. these include:

urinary‑free cortisol collection: two separate 24‑hour urine samples are collected to measure cortisol that is excreted in the urine.

blood pressure monitoring: an ambulatory blood pressure monitor (abpm) records your blood pressure over a 24‑hour period.

body weight measurement.

oral glucose tolerance test (ogtt): you drink a solution containing 75 g of glucose and blood samples are taken to see how your body handles sugar.

low‑dose dexamethasone suppression test (lddst) is not performed at baseline but will be done later in the study.

3 daily study medication

you take one film‑coated tablet each day by mouth.

the tablet contains either osilodrostat 60 mg (the active drug) or placebo 60 mg (an inactive substance).

the tablet is taken once daily for the entire 30‑week treatment period.

4 mid‑study visit (week 21)

at week 21 you return for a study visit that repeats many of the baseline measurements:

two 24‑hour urine collections for urinary‑free cortisol.

ambulatory blood pressure monitoring to assess blood pressure changes.

body weight measurement.

oral glucose tolerance test with a 75 g glucose drink.

low‑dose dexamethasone suppression test: you take a single 1 mg dexamethasone tablet in the evening and a blood sample is drawn the next morning to measure morning cortisol.

the daily study tablet continues to be taken as before.

5 final visit (week 30)

at the end of the 30‑week period you attend the final study visit. the same procedures as at week 21 are performed:

two 24‑hour urine collections for urinary‑free cortisol.

ambulatory blood pressure monitoring.

body weight measurement.

oral glucose tolerance test with 75 g glucose.

low‑dose dexamethasone suppression test with a 1 mg tablet.

the study medication is stopped after this visit.

Who Can Join the Study?

Be 18 years old or older.
Be able to sign a written consent form agreeing to join the study.
Have a diagnosis of endogenous Cushing’s syndrome — a condition that starts inside the body.
Show urinary free cortisol (UFC) results from two 24‑hour urine collections that are higher than the normal upper limit but not more than twice that limit (the normal upper limit is called ULN).
Have high blood pressure (hypertension) that is not fully controlled, be on stable blood‑pressure medicines for at least 4 weeks, and have a 24‑hour blood‑pressure monitor (ABPM) reading with an average systolic pressure (the top number) between 135 and 170 mmHg or a diastolic pressure (the bottom number) between 85 and 110 mmHg.
If you are taking glucocorticoid replacement therapy (a type of steroid medication), you must have stopped it for at least seven days or for five drug half‑lives (the time it takes for half the drug to leave your body), whichever is longer.
Not be using any medication to treat Cushing’s syndrome. If you have taken any of the following medicines, you must have stopped them for the required time before screening: steroid‑making blockers (e.g., ketoconazole, metyrapone) — 1 week; mifepristone — 3 weeks; subcutaneous pasireotide — 1 week; long‑acting pasireotide (LAR) — 3 months; cabergoline — 4 weeks.
Be able to swallow pills and be willing to follow the study’s schedule and procedures.

Who Cannot Join the Study?

You have taken the study medication osilodrostat less than 12 weeks before the screening visit.
You are known to be allergic (have a hypersensitivity reaction) to osilodrostat.
You have a severe or uncontrolled medical condition that could affect your safety or the study results.
You are scheduled to have surgery to treat Cushing’s syndrome within the next 32 weeks.
You have both high blood pressure (hypertension) and diabetes that have been present for more than 10 years before your Cushing’s syndrome diagnosis.
You have a history of cyclic Cushing’s syndrome, where symptoms come and go.
You have “pseudo‑Cushing’s syndrome,” a condition that mimics Cushing’s syndrome but is caused by something else.
You have a large pituitary tumor (macroadenoma) that is pressing on the optic chiasm (the part of the brain where the optic nerves cross) or you are at high risk for this compression.
You had pituitary or adrenal surgery for Cushing’s syndrome within the last 3 months.
You received radiation therapy to the pituitary gland within the past 3 years.
You have ectopic ACTH syndrome or adrenocortical carcinoma (a type of adrenal cancer) with a life expectancy of less than 3 years, or you are currently receiving chemotherapy.
You have previously been treated with the drug mitotane.
You work night shifts or have conditions that could interfere with tests that measure late‑night salivary cortisol (LNSC) or the low‑dose dexamethasone suppression test (LDDST).
You have poorly controlled diabetes, shown by a blood test (HbA1c) higher than 10.5%, or your diabetes medicines have not been at a stable dose for at least 4 weeks.
You have an underactive thyroid (hypothyroidism) and are not taking enough thyroid hormone replacement.
You had major surgery for any reason within the last 4 weeks and have not fully recovered.
You have a slow heart rate (bradycardia) or any heart rhythm problems that affect the QT interval (a measure of heart electrical activity).
Your blood tests show a total bilirubin level more than 1.5 times the normal upper limit, or liver enzymes ALT or AST more than 3 times the normal upper limit.
You have taken part in another clinical study or used an investigational drug within the last 4 weeks (or longer if required by local rules).
You have had a serious acute illness within the last 3 weeks before the study start.
You are pregnant, planning to become pregnant, breastfeeding, or have a positive pregnancy test (hCG).
You are a woman who could become pregnant and are unwilling to use highly effective birth control methods.
You are considered unreliable or vulnerable (for example, a person in detention) or the investigator judges you unsuitable for the study.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Centre Hospitalier Universitaire De Lille	Lille	France
Technische Universitaet Dresden	Dresden	Germany
Uniwersytecki Szpital Kliniczny Im Jana Mikulicza Radeckiego We Wroclawiu	Wroclaw	Poland
Szpital Bielanski Im.Ks.Jerzego Popieluszki samodzielny publiczny zakład opieki zdrowotnej	Warsaw	Poland
Spitalul Clinic Judetean De Urgenta Cluj	Cluj Napoca	Romania

Other Sites

Site Name	City	Country
Hopital Beaujon	Clichy	France
Hospital Universitari De Girona Doctor Josep Trueta	Girona	Spain
Uniwersyteckie Centrum Stomatologii I Medycyny Specjalistycznej Sp. z o.o.	Poznan	Poland
Hospital General Universitario Gregorio Maranon	Madrid	Spain
Instytut Centrum Zdrowia Matki Polki	Lodz	Poland
Spitalul Clinic Judetean De Urgenta Pius Brinzeu Timisoara	Timisoara	Romania
Atzvntt Opdfumeluro dw Povzuq	Padua	Italy
Flvgwoekfo Ildrn Cx Gftmgc Ofvsvjyn Marwinbl Pttqtondiuy	Milan	Italy
Arvu Gauexs Oqmnvbqy Mpebtdcezgrqr Nlimvxxi	Milan	Italy
Anztqkswhi Ptneenic Hlheyojg Dj Meqcxqrrc	Marseille	France
Afyouxe Owhedwbifew Usozwenrysfmp Cbauteiaphds Dults Smubel E Dixlw Sauydgh Dr Tyilmn	Turin	Italy
Awpeqpp Ohffljnwmce Ufttlstfosjgq Fnnuxniv It Do Nabvxf	Naples	Italy
Gubtqd Urjlifgppt Fcymuxxby	Frankfurt	Germany
Kscxjyuw dbn Udsiytrjmnkb Mtpzpjdv Aau	Munich	Germany
Ctmrlq Hlvrqstvpvr Upvzoycqssecg Akwthu Pnkbtndk	Amiens	France
Ahjyall Uitmp Stczpmvig Lnzeex Da Bklvzzz	Bologna	Italy
Cpjqws Hbmmjwrxnkl Ukfllugytdtfc Rtpgi	Reims	France
Uuawbonyiy Dzdmb Sykkd Db Rmed Ln Snnfeaom	Rome	Italy
Csbnzy Hognpixjvzw Ldhw Srr	Pierre Benite	France
Keiabmuh Bqtyelycq ghvvl	Bielefeld	Germany
Hrkzdxon Ujztfipsodruab Sfuwvaubqj &pyhggr Hipizrq da Huptpmsiscm	STRASBOURG, Alsace	France
Mioojjb Chhqzq Averz Ijk Pqjaite Eiqq	Sofia	Bulgaria
Hyihjukk Vfvc dknvrdng	Barcelona	Spain
Duvpsglnzhpbidnhjovoxfz cwiiaf “kwmnhnllhmxarpf Ejkp	Sofia	Bulgaria
Vtikpd dky Rfqxb Uqvnagkrfr Hppfusdd	Sevilla	Spain
Hqgomlrw Cxikmx Dl Bqwxztmng	Barcelona	Spain
Spqgszojssb Pmhtdppiz Zdlmom Oybmbg Zsnfidqzmf Stewdef Unbwzsdhccowh W Kzztikuq	Cracow	Poland
Ndukiudd Irrdbrbj Olhffrygp Ini Mpgzb Szvyrxlteiqctgppcpzmuxeaoonx Ibezpajr Bfojfnxn	Cracow	Poland
Mkjrlsbbql Stgnvmf Btyvaoyzxm Suh z opur	Warsaw	Poland
Eukvxugwn Ijdskwdhg Fxq Ckbohfxhrlotbq Dujmwsgh Ahf Tcutocpbjk	Targu Mures	Romania
Nshawdcq Ipfezkolg Of Egptrtknngxev Cjuy Pbhekt	Bucharest	Romania

Trial status

Country	Status	Recruitment Start
Bulgaria	Not yet recruiting	01.09.2026
France	Not yet recruiting	01.09.2026
Germany	Not yet recruiting	01.09.2026
Italy	Not yet recruiting	01.09.2026
Poland	Not yet recruiting	01.09.2026
Romania	Not yet recruiting	01.09.2026
Spain	Not yet recruiting	01.09.2026

Trial locations

Investigated Drugs:

Osilodrostat is an oral tablet that works by blocking an enzyme needed for the body to make cortisol, the stress hormone. In this study, it is being tested to see if it can lower the high blood pressure that occurs when too much cortisol is produced in Cushing’s syndrome. Participants take the medicine regularly, and doctors monitor how well it reduces cortisol levels and improves blood pressure.

Glucose is a simple sugar given by mouth during the trial. It is used as a background substance to help assess how the body processes sugar and to provide a consistent reference point for other measurements in the study.

Dexamethasone is a low‑dose steroid tablet taken by participants as part of their usual treatment. In this trial, it serves as background therapy to manage inflammation and other symptoms while the researchers focus on the effect of the test medication.

Investigated Diseases:

Cushing's syndrome

Cushing’s syndrome – Cushing’s syndrome is a condition in which the body is exposed to too much cortisol over a prolonged period. The excess cortisol can come from the adrenal glands themselves or from external sources. Over time, the high hormone levels cause the body to store more fat, especially around the abdomen and face, and to develop thin skin that bruises easily. Muscle strength may decrease and bones can become weaker, leading to aches and fractures. Blood pressure and blood sugar levels often rise as the disease continues. Without treatment, the hormonal imbalance tends to persist and can worsen these changes.

Trial ID:

2025-524649-28-00

Protocol code:

LCI699-RECAG-CL-0615

NCT ID:

NCT07247162

Trial Phase:

Therapeutic confirmatory (Phase III)

Other Trials to Consider

#1 Clinical Trials Search in Europe

Efficacy and safety of osilodrostat with drug combination in patients with hypertension caused by Cushing’s syndrome

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?