Skip to content
Clinical Trials – home

Rare diseases

Investigational molecules

Locations

Our offerNewsroom

Not yet recruitingRare disease

Efficacy and Safety of Atumelnant, Hydrocortisone and Prednisone in Adults with ACTH‑Dependent Cushing’s Syndrome: A Phase 2/3 Dose‑Finding Study

Verified siteRegistered drug
Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Featured sites

Sites that work closely with us on this trial

What is this trial about?

A plain-language summary of the goals, design and what participants do

The study focuses on adults with ACTH-Dependent Cushing’s Syndrome, a rare condition in which the body produces excess cortisol because of overstimulation by the pituitary gland (Pituitary-dependent Cushing’s syndrome). The medication being tested is Atumelnant, an oral tablet given in several dose levels, while some participants will receive a dummy pill (placebo) for comparison.

The main purpose is to determine whether Atumelnant can reduce the amount of cortisol eliminated in urine, measured as mUFC (mean urinary free cortisol), after 12 weeks of treatment. Participants will take the study drug daily for about three months, with clinic visits at the start, during treatment, and at the end to collect urine, blood and saliva samples and to complete quality‑of‑life questionnaires. After this initial phase, an open‑label extension allows continued use of the active drug for longer‑term safety monitoring, with the same type of follow‑up visits.

The research process

The trial runs in 5 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Baseline visit

    At the first visit after joining the study, you will provide urine, blood and saliva samples. these samples are used to measure mean urinary free cortisol (mufc), morning serum cortisol and late‑night salivary cortisol. you will also complete a questionnaire that evaluates your quality of life. the results create a baseline for later comparison.

  2. Step 2

    Randomization and start of study medication

    Based on the study design, you will be assigned to receive either atumelnant tablets or a matching placebo. the specific dose of atumelnant (20 mg, 40 mg, 80 mg or 120 mg) is decided by the study investigators. the tablets are taken by mouth.

    If you are assigned to the placebo group, you will receive an inactive tablet that looks identical to the active medication.

  3. Step 3

    Daily medication for twelve weeks

    You will take the assigned tablet once each day for a total of twelve weeks. the dose remains the same throughout this period. for example, if you are assigned to the 80 mg group, you will take one 80 mg atumelnant tablet each day.

    The study also allows the use of background medication such as low‑dose hydrocortisone or prednisone tablets if needed for adrenal insufficiency. these background tablets are taken as directed by the study team and are recorded in your study diary.

    Regular safety checks are scheduled every two to four weeks. during these visits, you will provide additional blood or urine samples and report any side effects.

  4. Step 4

    Week‑12 evaluation

    At the end of week twelve, you will return for a comprehensive assessment. the same cortisol measurements (urine, blood and saliva) and quality‑of‑life questionnaire are repeated.

    The primary goal of the study is to determine whether your mean urinary free cortisol is at or below the upper limit of normal (uln) after twelve weeks of treatment.

  5. Step 5

    Open‑label extension (optional)

    If you choose to continue, you may enter an open‑label extension where all participants receive active atumelnant. the dose used in the extension is the same as the dose you received during the first twelve weeks.

    During the extension, you will continue daily dosing and attend periodic follow‑up visits to monitor long‑term safety and effectiveness.

Who can join the trial?

8 criteria

  • Be a man or woman who is at least 18 years old but younger than 75 years when signing the consent form (people 16‑17 can join only at U.S. sites).
  • Have a confirmed diagnosis of ACTH‑dependent Cushing’s syndrome (the type caused by excess ACTH from the pituitary, an ectopic source, or an unknown source) proven by laboratory tests.
  • Show a mean urinary free cortisol (mUFC) level that is more than 1.3 times the normal upper limit, measured before the first study day.
  • Have a record of either an abnormal dexamethasone suppression test or high late‑night salivary cortisol levels taken in the past, or a tissue test that proved an ACTH‑producing tumor.
  • Have a morning blood level of ACTH greater than 10 pg/mL.
  • Stop (wash out) any current medicines used for treating ACTH‑dependent Cushing’s syndrome for the required time before baseline measurements: at least 2 weeks for ketoconazole, levoketoconazole, or metyrapone; at least 4 weeks for osilodrostat, mifepristone, or cabergoline; and at least 8 weeks for pasireotide LAR.
  • For participants moving to the later part of the study (Part C), you must have finished the 12‑week treatment period in Part A or Part B, or have been rescued because of high cortisol, and the doctor believes you could benefit from continuing.
  • If enrollment in Part B is closed, you may join Part C directly if you were already being screened for Part B and meet all the Part B requirements.

Who cannot join the trial?

11 criteria

  • Allergy to the study drug: You cannot take part if you have ever had an allergic reaction (hypersensitivity) to atumelnant or any of its inactive ingredients (excipients).
  • Recent use of certain medicines: If you have taken any of the following drugs within the required time before screening, you are not eligible: ketoconazole, levoketoconazole, or metyrapone within the past 2 weeks; osilodrostat, mifepristone, or cabergoline within the past 4 weeks; pasireotide LAR within the past 8 weeks. This “washout” period is needed so the medicines do not affect the study.
  • Use of other experimental drugs: You may not have taken any other investigational (experimental) medication in the last 60 days or for a period equal to five half‑lives of that drug (whichever is longer), and you cannot be planning to join another experimental study.
  • Previous mitotane use: Anyone who has ever taken the drug mitotane is excluded.
  • Recent major surgery: You must not have had any major operation (such as abdominal or heart surgery) within 1 month before the screening visit.
  • Recent pituitary surgery: If you had surgery on the pituitary gland within the past month, you cannot join the trial.
  • Recent pituitary radiation: You are excluded if you received radiation therapy to the pituitary gland in the last 3 years.
  • High‑risk pituitary tumor features: You cannot participate if any of the following are true: a brain scan (MRI) shows a pituitary tumor that is very close (within 2 mm) to the optic chiasm (where the optic nerves cross); the tumor has grown again within 1 year after surgery or radiation; doctors expect you will need brain surgery or radiation during the study; or you have pituitary carcinoma (a cancer of the pituitary gland).
  • Previous use of atumelnant: Anyone who has taken the study drug atumelnant before is not allowed to enroll.
  • Limited expected benefit or short life expectancy: If the investigator believes the drug will not help you, or if you are expected to live less than 6 months, you are excluded.
  • Other serious health problems: Any other significant medical condition that the investigator thinks could make participation unsafe or affect the study results will disqualify you.
Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Tell us about your condition – we search every trial in Europe and connect you with the right site.

We usually reply within a few days

Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

Trial locations

Where you can join this trial

Countries are shaded by recruitment status. Click a recruiting country to ask about joining there.

Not yet recruiting
Not finding your country?

Not sure what to do next?

Joining a clinical trial can seem overwhelming. We guide you step by step, so you know exactly what to expect and how we support you through the process.

See the full process and FAQ

Investigated drugs

  • Prednisone

    is a short‑acting steroid pill that reduces inflammation and suppresses the immune system. In this study it is given as a test medication to see how well it controls the excess cortisol production that occurs in ACTH‑dependent Cushing’s syndrome. Participants take the tablets by mouth, and the researchers compare its effects with those of the new drug being tested.

  • Hydrocortisone (oral tablets)

    is a steroid medication that works similarly to the body’s natural cortisol. In the trial, participants receive hydrocortisone tablets to help manage their hormone levels while the new treatment is being evaluated. The tablets are taken by mouth and serve as an additional test drug to assess how it performs compared with the investigational therapy.

  • Hydrocortisone (injectable solution)

    is a liquid form of the same steroid that can be given by injection. In this study it is used as background therapy, meaning it is provided to all participants to ensure a basic level of hormone replacement. The injection is prepared from a powder that is mixed with a solvent before use, and it helps keep patients stable while the experimental drug’s effectiveness is measured.

  • Atumelnant

    is the investigational drug being studied for the first time in people with ACTH‑dependent Cushing’s syndrome. It is taken as a tablet taken by mouth and is intended to lower the amount of cortisol the body makes. The trial tests several different dose levels of atumelnant to find the amount that works best with the fewest side effects, and its impact on cortisol levels is measured after 12 weeks.

What is already known about the treatment

  • Prednisone

    Prednisone is taken by mouth as a tablet, usually 5 mg, and is an approved corticosteroid that has been used for many years to treat inflammation and immune‑related conditions. It is commonly prescribed for asthma, arthritis, skin disorders, and other inflammatory diseases. The medicine works by entering cells and attaching to glucocorticoid receptors, which then switch off genes that cause swelling and pain. It belongs to the glucocorticoid class of steroid drugs.

  • Hydrocortisone

    Hydrocortisone is available as an oral tablet (10–20 mg) and also as a powder that can be mixed for injection, and it is a well‑established corticosteroid used to replace missing cortisol and to reduce inflammation. It is used for adrenal insufficiency, allergic reactions, and various inflammatory conditions. The drug acts by binding to glucocorticoid receptors in the body, mimicking the natural hormone cortisol and turning down the inflammatory response. It is classified as a glucocorticoid steroid.

  • Atumelnant

    Atumelnant is taken by mouth as a tablet in doses ranging from 20 mg to 120 mg and is currently being studied in phase 2/3 trials for adults with ACTH‑dependent Cushing’s syndrome. It is an investigational drug that is not yet approved for general medical use. The compound works by blocking the action of excess cortisol at its receptor, helping to lower the high hormone levels that cause the disease. It is classified as an experimental glucocorticoid‑receptor modulator.

Investigated diseases

  • ACTH-dependent Cushing's syndrome

    A hormonal disorder in which excess adrenocorticotropic hormone (ACTH) drives the adrenal glands to produce too much cortisol. The elevated cortisol gradually leads to weight gain, especially around the trunk, and a round face. Skin may become thin and develop easy bruising or stretch marks. Muscle strength can decline, making everyday tasks more tiring. Blood sugar levels often rise, and blood pressure may increase as the condition progresses.

  • Pituitary-dependent Cushing's syndrome

    Also known as Cushing's disease, it results from a pituitary tumor that secretes excess ACTH, stimulating excess cortisol production. The rising cortisol causes progressive central obesity, a rounded facial appearance, and fat deposits on the back of the neck. Skin changes such as thinning and purple stretch marks become more noticeable over time. Patients may experience muscle weakness and reduced stamina. High cortisol also contributes to higher blood pressure and elevated blood sugar as the disease advances.

Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IVTrial ID2025-522648-42-01Protocol codeCRN04894-331Estimated enrolment190 patientsSponsorCrinetics Pharmaceuticals Inc.

sourced from the EU Clinical Trials Register and site verification

Want to learn more about this trial or check if you can participate?

Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Tell us about your condition – we search every trial in Europe and connect you with the right site.