Cushing SyndromePhase 2NCT03708900
Pharmacokinetic (PK), Pharmacodynamic (PD) and Tolerability of Osilodrostat in Pediatric Patients With Cushing's Syndrome
A Phase 2 study testing LCI699 in people with Cushing Syndrome, run by RECORDATI GROUP at 15 sites in 7 countries.
Trial summary
Multicenter, open-label, non-comparative study to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of osilodrostat in children and adolescent patients with Cushing's syndrome. Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Cushing Syndrome
- What is being tested?
- LCI699
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 15 sitesin 7 countries
- Study dates
- 28 Apr 2021to 21 Jul 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male and female children and adolescents from 2 to < 18 years of age with Cushing's syndrome of endogenous origin: Who have failed surgery (or) who are awaiting surgery (or) for whom surgery is not an immediate option. For patients who are awaiting surgery, the study treatment could be less than 12 weeks.
- Patients must weigh > 10 kg.
- The diagnosis of Cushing's syndrome must be confirmed by each of the following:
- 3a) The clinical criterion of decreasing growth percentiles with increasing weight (as evidenced by the presence of a contrast in height and BMI SD scores, for example a SDS < 0 and BMI SDS > 0, or a strong clinical suspicion of Cushing's syndrome, such as photographic evidence of a change in facial appearance); 3b) Abnormal low-dose (0.5 mg Q6h x 48 hours, or overnight 15mcg/kg [max 1 mg]) dexamethasone suppression test, defined as plasma cortisol levels > 1.8 mcg/dl, at time point 48 hours (0.5 mg Q6h x 48 hours) or 9 to 12 hours (overnight 15mcg/kg [max 1 mg]) after the first dose of dexamethasone; (OR) Midnight serum cortisol levels > ULN, assessed while the patient is sleeping and after pre-cannulation (OR) two samples of late-night salivary cortisol greater than ULN for the assay. 3c)Two 24-hour urinary free cortisol values > 1.3 x ULN;
- 4. Able to swallow study drug tablets (not crushed or split) or the content of the capsules mixed with water.
- 5. Parents or legal guardians able to provide consent/assent.
Who cannot join
- Patients with macroadenoma complicated by compressive symptoms (requiring urgent surgical intervention) or at high risk for compressive symptoms due to mass effect of tumor (concern of corticotroph tumor progression).
- Insufficient washout period from any other medication used to lower cortisol levels (5 half-lives of any drug).
- Use of other investigational drugs at the time of enrollment, or within 30 days, or prior to completion of a wash-out duration that is at least 5 half- lives of the drug, at the time of enrollment, whichever is longer. Local regulations may require a longer wash-out period or specify other limitations for participation in an investigational trial, in which case they will be applicable as well.
- History of hypersensitivity to drugs of the same or similar chemical classes as osilodrostat.
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
- Patients with moderate to severe renal impairment (estimated GFR < 60 mL/min by the Creatinine-based "Bedside Schwartz" equation).
Show all 21Show fewer
- Patients with serum ALT and/or AST > 3 x ULN, or total bilirubin > 1.5 x ULN.
- History of thrombosis.
- Patients with risk factors for QTc prolongation or Torsade de Pointes, including: 9a) patients with a baseline QTcF > 450 ms 9b) personal or family history of long QT syndrome 9c) concomitant medications known to prolong the QT interval 9d) patients with hypokalemia, hypocalcaemia, or hypomagnesaemia, if not corrected before pre-dose Day 0. In case of uncorrected hypokalemia (<3.5 mEq/L), the screening period may be used to correct hypokalemia prior to starting study drug. Use of potassium supplements and/or mineralocorticoid antagonists is permitted during the study. 9e) Patients with a history of significant cardiovascular disease (based on the opinion of the investigator) such as: structural cardiovascular abnormalities, arrhythmia,
- Hypertensive patients with uncontrolled blood pressure defined as SBP > 150 and/or DBP > 100 or not optimally treated for hypertension as judged by the investigator.
- Patients who have undergone any major surgery within 1 month.
- Patients who have undergone trans-sphenoidal pituitary surgery within 6 weeks prior to screening are not eligible, unless they have clear evidence of persistent hypercortisolism or persistent biochemical changes consistent with Cushing's syndrome.
- Use of or anticipated use of systemic glucocorticoid medications 1 month prior to screening.
- Uncontrolled hypothyroidism as evidenced by Free T4 < 0.8 ng/dl.
- Uncontrolled hyper thyroidism.
- Diabetic patients with poorly controlled diabetes as evidenced by HbA1c > 8.5 % or not optimally treated for diabetes mellitus as judged by the investigator.
- Positive pregnancy test in females of childbearing potential.
- Female patients of childbearing potential who do not agree to use highly effective birth control methods .
- Pregnant or nursing (lactating) women.
- Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures. Any severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for the study.
- Use of concomitant prohibited medications
Trial locations and contacts
15 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
Recordati contact
15 sites in 7 countries
United States5 sites, 4 recruiting
- Completed
National Institute of Child Health and Human Development
Bethesda, Maryland, 20892
- Recruiting
ABMED Clinical Research Corp
Cape Coral, Florida, 33914
Paige Vanier Kreegel, Dr, dacosta@abmedclinicalresearch.com
- Recruiting
Ann & Robert H. Lurie Children's Hospital
Chicago, Illinois, 60611
Emily Marshall, Dr, emarshall@luriechildrens.org
Wendy Brickman
- Recruiting
University of California San Francisco UCSF
San Francisco, California, 94143
Maya Lodish, 415-476-3310, maya.lodish@ucsf.edu
- Recruiting
Texas Valley Clinical Research
Weslaco, Texas, 78596
Eduardo Dusty Luna, Dr, Hale.rn@tvcrtrials.com
France3 sites
- Completed
Hospital Necker Enfants Malades
Paris, 75015
- Completed
Robert Debre Hospital
Paris, 75019
- Completed
CHU Bicetre APHP Paris Saclay
Paris, 94270
Italy2 sites
- Completed
Aziendal Ospedaliero Universitaria Pisana Presidio Ospedale di Cisanello
Pisa, PI, 56124
- Completed
Ospedale Bambino Gesu
Roma, 00165
United Kingdom2 sites
- Withdrawn
Alder Hey Childrens NHS Foundation Trust
Liverpool, L12 2AP
- Withdrawn
The Royal London Childrens Hospital
London, E11BB
Bulgaria1 site
- Withdrawn
Multiprofile Hospital for Active Treatment Sveta Marina EAD
Varna, 9010
About this study
Official title: A Phase II, Multicenter, Open-label, Non-comparative Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Tolerability of Osilodrostat in Children and Adolescent Patients With Cushing's Syndrome
Multicenter, open-label, non-comparative study to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of osilodrostat in children and adolescent patients with Cushing's syndrome.
Read the detailed description
The period 1 study duration will be 12 weeks. The study will include a screening period of up to 4 weeks prior to Day 0 (baseline) (to allow for an adequate washout period from any medications that may modify cortisol levels). All subjects being treated with osilodrostat at 12 weeks and obtaining benefit from therapy, per investigator judgment, will be offered participation in an optional 9-month extension period, during which assessment of the PD activity and safety/tolerability of osilodrostat will be done. Patients who do not enter the optional extension period will have a safety follow up visit 4 weeks later.
- Conditions
- Cushing Syndrome
- Being tested
- LCI699
- Keywords
- Cushing's syndrome (CS), LCI699, osilodrostat, Pituitary Gland, Adrenocorticotropic Hormone (ACTH), Urinary Free Cortisol (UFC), mean Urinary Free Cortisol (mUFC)
- Medical subject headings
- Cushing Syndrome, Pituitary Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LCI699Drug
Also called osilodrostat
osilodrostat (LCI699) is in the form of tablets 1 milligram (mg), 5 mg, and 10mg or in form of capsules 0.1 mg, 0.2 mg, 0.5 mg, 1 mg or 5 mg, both the formulations for oral administration
| Study group | Role | What they receive |
|---|---|---|
| LCI699 (osilodrostat) | Experimental | Subjects with cushing's syndrome taking LCI699 (osilodrostat) Receives: Drug: LCI699 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Core Study: Evaluate the pharmacokinetics (PK) of osilodrostat using Pharmacokinetic parameters of osilodrostat up to Week 12 in children and adolescents 2 to less than 18 years of age with Cushing's Syndrome
evaluate the pharmacokinetics (PK) of osilodrostat in children and adolescents of 2 to less than 18 years of age with Cushing's Syndrome
Measured: up to Week 12
Secondary outcomes (10)
Core Study: Percentage of patients with normal mean urinary free cortisol (mUFC) at week 3, 6, 9 and week 12 (or end of treatment)
The assessment in the core period will be done by taking the percentage of patients with normal mUFC at week 6 and week 12 (or end of treatment).
Measured: week 3, 6, 9 and week 12 (or end of treatment)
Core Study: Change from baseline in mean urinary free cortisol (mUFC) during the core study period
The assessment will be done by comparison of change from the baseline in mUFC during core study period on patients
Measured: week 3, 6, 9 and week 12 (or end of treatment)
Extension: Efficacy of osilodrostat as measured by mUFC levels up to Month 12
The assessment of efficacy of osilodrostat to be measured by change in baseline of mUFC levels up to 12 months on patients
Measured: up to month 12
Extension: Efficacy of osilodrostat as measured by mUFC levels up to Month 12
The assessment of efficacy of osilodrostat to be measured byproportion of patients with normal mUFC levels at each visit up to 12 months
Measured: up to month 12
assessment of the pharmacodynamics, safety and tolerability of osilodrostat.
Change from baseline in weight in core period
Measured: week 3, 6, 9 and week 12 (or end of treatment)
assessment of the pharmacodynamics, safety and tolerability of osilodrostat up to 12 months
Change from baseline in weight at each visit in extension period
Measured: up to 12 months
assessment of the pharmacodynamics, safety and tolerability of osilodrostat.assessment of the pharmacodynamics, safety and tolerability of osilodrostat.
Change from baseline in body mass index in core period
Measured: week 3, 6, 9 and week 12 (or end of treatment)
assessment of the pharmacodynamics, safety and tolerability of osilodrostat.assessment of the pharmacodynamics, safety and tolerability of osilodrostat.
Change from baseline in body mass index at each visit in extension period
Measured: up to 12 months
assessment of the pharmacodynamics, safety and tolerability of osilodrostat.
Change from baseline in height in core period
Measured: week 3, 6, 9 and week 12 (or end of treatment)
assessment of the pharmacodynamics, safety and tolerability of osilodrostat.
Change from baseline in height at each visit in extension period
Measured: up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2018
- Study start28 Apr 2021
- Primary completion21 Jul 2027 (estimated)
- Study completion21 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cushing SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RECORDATI GROUP
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Recordati AG, Study director, Recordati AG
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03708900
- Sponsor's protocol ID
- CLCI699C2203
- Other IDs
- 2018-001522-25, 2018
- Status last verified
- Mar 2026
- First submitted
- 8 Oct 2018
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Multicenter, Open-label, Non-comparative Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Tolerability of Osilodrostat in Children and Adolescent Patients With Cushing's Syndrome
- ClinicalTrials.gov ID
- NCT03708900
- Acronym / sponsor ID
- CLCI699C2203
- Conditions
- Cushing Syndrome
- Keywords
- Cushing's syndrome (CS), LCI699, osilodrostat, Pituitary Gland, Adrenocorticotropic Hormone (ACTH), Urinary Free Cortisol (UFC), mean Urinary Free Cortisol (mUFC)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- RECORDATI GROUPIndustry (pharma, biotech, devices)
- Study start
- 28 Apr 2021 (actual)
- Primary completion
- 21 Jul 2027 (estimated)
- Study completion
- 21 Jul 2027 (estimated)
- First posted
- 17 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multicenter, open-label, non-comparative study to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of osilodrostat in children and adolescent patients with Cushing's syndrome.
Detailed description
The period 1 study duration will be 12 weeks. The study will include a screening period of up to 4 weeks prior to Day 0 (baseline) (to allow for an adequate washout period from any medications that may modify cortisol levels). All subjects being treated with osilodrostat at 12 weeks and obtaining benefit from therapy, per investigator judgment, will be offered participation in an optional 9-month extension period, during which assessment of the PD activity and safety/tolerability of osilodrostat will be done. Patients who do not enter the optional extension period will have a safety follow up visit 4 weeks later.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LCI699 (osilodrostat) | Experimental | Drug: LCI699Subjects with cushing's syndrome taking LCI699 (osilodrostat) |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Male and female children and adolescents from 2 to < 18 years of age with Cushing's syndrome of endogenous origin: Who have failed surgery (or) who are awaiting surgery (or) for whom surgery is not an immediate option. For patients who are awaiting surgery, the study treatment could be less than 12 weeks.
- Patients must weigh > 10 kg.
- The diagnosis of Cushing's syndrome must be confirmed by each of the following:
- 3a) The clinical criterion of decreasing growth percentiles with increasing weight (as evidenced by the presence of a contrast in height and BMI SD scores, for example a SDS < 0 and BMI SDS > 0, or a strong clinical suspicion of Cushing's syndrome, such as photographic evidence of a change in facial appearance); 3b) Abnormal low-dose (0.5 mg Q6h x 48 hours, or overnight 15mcg/kg [max 1 mg]) dexamethasone suppression test, defined as plasma cortisol levels > 1.8 mcg/dl, at time point 48 hours (0.5 mg Q6h x 48 hours) or 9 to 12 hours (overnight 15mcg/kg [max 1 mg]) after the first dose of dexamethasone; (OR) Midnight serum cortisol levels > ULN, assessed while the patient is sleeping and after pre-cannulation (OR) two samples of late-night salivary cortisol greater than ULN for the assay. 3c)Two 24-hour urinary free cortisol values > 1.3 x ULN;
- 4. Able to swallow study drug tablets (not crushed or split) or the content of the capsules mixed with water.
Key exclusion criteria (21 listed)
- Patients with macroadenoma complicated by compressive symptoms (requiring urgent surgical intervention) or at high risk for compressive symptoms due to mass effect of tumor (concern of corticotroph tumor progression).
- Insufficient washout period from any other medication used to lower cortisol levels (5 half-lives of any drug).
- Use of other investigational drugs at the time of enrollment, or within 30 days, or prior to completion of a wash-out duration that is at least 5 half- lives of the drug, at the time of enrollment, whichever is longer. Local regulations may require a longer wash-out period or specify other limitations for participation in an investigational trial, in which case they will be applicable as well.
- History of hypersensitivity to drugs of the same or similar chemical classes as osilodrostat.
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LCI699Also: osilodrostatosilodrostat (LCI699) is in the form of tablets 1 milligram (mg), 5 mg, and 10mg or in form of capsules 0.1 mg, 0.2 mg, 0.5 mg, 1 mg or 5 mg, both the formulations for oral administration | Drug | LCI699 (osilodrostat) |
Primary outcome
Core Study: Evaluate the pharmacokinetics (PK) of osilodrostat using Pharmacokinetic parameters of osilodrostat up to Week 12 in children and adolescents 2 to less than 18 years of age with Cushing's Syndrome
Time frame: up to Week 12
evaluate the pharmacokinetics (PK) of osilodrostat in children and adolescents of 2 to less than 18 years of age with Cushing's Syndrome
10 secondary outcomes
Core Study: Percentage of patients with normal mean urinary free cortisol (mUFC) at week 3, 6, 9 and week 12 (or end of treatment)
Time frame: week 3, 6, 9 and week 12 (or end of treatment)
Core Study: Change from baseline in mean urinary free cortisol (mUFC) during the core study period
Time frame: week 3, 6, 9 and week 12 (or end of treatment)
Extension: Efficacy of osilodrostat as measured by mUFC levels up to Month 12
Time frame: up to month 12
Extension: Efficacy of osilodrostat as measured by mUFC levels up to Month 12
Time frame: up to month 12
assessment of the pharmacodynamics, safety and tolerability of osilodrostat.
Time frame: week 3, 6, 9 and week 12 (or end of treatment)
assessment of the pharmacodynamics, safety and tolerability of osilodrostat up to 12 months
Time frame: up to 12 months
assessment of the pharmacodynamics, safety and tolerability of osilodrostat.assessment of the pharmacodynamics, safety and tolerability of osilodrostat.
Time frame: week 3, 6, 9 and week 12 (or end of treatment)
assessment of the pharmacodynamics, safety and tolerability of osilodrostat.assessment of the pharmacodynamics, safety and tolerability of osilodrostat.
Time frame: up to 12 months
assessment of the pharmacodynamics, safety and tolerability of osilodrostat.
Time frame: week 3, 6, 9 and week 12 (or end of treatment)
assessment of the pharmacodynamics, safety and tolerability of osilodrostat.
Time frame: up to 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- Individual participant dataSharing planned: Yes
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Automated Capture of Core Data for Rare Diseases and Glucocorticoid Complications: Biomarkers and Patient-Reported Outcomes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Recordati contact
Recordati AG study director
Recordati AG
15 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LCI699 in people with Cushing Syndrome, run by RECORDATI GROUP at 15 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, France, Italy, United Kingdom, Belgium and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Recordati (+39 0248787456, casi.m@recordati.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Core Study: Evaluate the pharmacokinetics (PK) of osilodrostat using Pharmacokinetic parameters of osilodrostat up to Week 12 in children and adolescents 2 to less than 18 years of age with Cushing's Syndrome (time frame: up to Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2026.