Pharmacokinetic (PK), Pharmacodynamic (PD) and Tolerability of Osilodrostat in Pediatric Patients With Cushing's Disease

Cushing's Disease Clinical Trial

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 Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03708900
• Other study ID #: CLCI699C2203
• Secondary ID: 2018-001522-25
• Status: Recruiting
• Phase: Phase 2
• Start date: April 28, 2021
• Est. completion date: November 21, 2025

Study information

• Verified date: May 2024
• Source: RECORDATI GROUP
• Contact: Recordati
• Phone: +390248787456
• Email: casi.m[@]recordati.it
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 disease.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: November 21, 2025
• Est. primary completion date: November 21, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

Inclusion Criteria:

• Cushing's disease of endogenous origin: Who have failed surgery (or) who are awaiting surgery (or) for whom surgery is not an immediate option.

• The diagnosis of Cushing's disease must be confirmed by each of the following:

• The clinical criterion of decreasing growth percentiles with increasing weight (as evidenced by the presence of a contrast in height and BMI standard deviation (SD) scores, defined as height standard deviation score (SDS) < 0 and BMI SDS > 0, and a strong clinical suspicion of Cushing's disease, such as photographic evidence of a change in facial appearance);

• Abnormal low-dose (0.5 mg Q6h x 48 hours) dexamethasone suppression test, defined as plasma cortisol levels > 1.8 mcg/dl, at time point 48 hours after the first dose of dexamethasone;

• Measurable morning ACTH levels, assessed before 10 am;

• Two 24-hour urinary free cortisol values > 1.3 x ULN

• If the dexamethasone suppression test does not meet the above mentioned criteria, the diagnosis of Cushing's disease may be confirmed by the following: Midnight serum cortisol levels > upper limit of normal (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

• Able to swallow study drug tablets (not crushed or split)

• Parents or legal guardians able to provide consent/assent

Exclusion Criteria:

• 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)

• Hypercortisolism not due to Cushing's disease

• 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.

• Body weight <30kg

Other protocol-defined inclusion/exclusion may apply.

Related Conditions & MeSH terms

• ACTH-Secreting Pituitary Adenoma
• Cushing's Disease
• Pituitary ACTH Hypersecretion

Intervention

Drug:
• LCI699
osilodrostat (LCI699) is in the form of tablets for oral administration and comes in the following tablet strengths: 1 milligram (mg), 5 mg, and 10mg.

Locations

Country	Name	City	State
Belgium	UZ Brussel	Jette	Brussel
Bulgaria	Multiprofile Hospital for Active Treatment Sveta Marina EAD	Varna
France	CHU Bicetre APHP Paris Saclay	Paris
France	Hospital Necker Enfants Malades	Paris
France	Robert Debre Hospital	Paris
Italy	Aziendal Ospedaliero Universitaria Pisana Presidio Ospedale di Cisanello	Pisa	PI
Italy	Ospedale Bambino Gesu	Roma
Slovenia	University Clinical Center Ljubljana	Ljubljana
United Kingdom	Alder Hey Childrens NHS Foundation Trust	Liverpool
United Kingdom	The Royal London Childrens Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
RECORDATI GROUP

Countries where clinical trial is conducted

Belgium,  Bulgaria,  France,  Italy,  Slovenia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Core Study: Evaluate the pharmacokinetics (PK) of osilodrostat using Pharmacokinetic parameter - Cmax - of osilodrostat up to Week 12 in children and adolescents 6 to less than 18 years of age with Cusihing's Disease	evaluate the pharmacokinetics (PK) by Cmax of osilodrostat in children and adolescents 6 to less than 18 years of age with Cushing's Disease	up to Week 12
Primary	Core Study: Evaluate the pharmacokinetics of osilodrostat using Pharmacokinetic parameter - Ctrough - of osilodrostat up to Week 12 in children and adolescents 6 to less than 18 years of age with Cushing's Disease	evaluate the pharmacokinetics (PK) by Ctrough of osilodrostat in children and adolescents 6 to less than 18 years of age with Cushing's Disease	up to Week 12
Secondary	Core Study: Percentage of patients with normal mean urinary free cortisol (mUFC) at week 6 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).	week 6, week 12 (or end of treatment)
Secondary	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	Baseline, 12 weeks
Secondary	Extension: Efficacy of osilodrostat as measured by mUFC levels up to Month 12	The assessment of efficacy of osilodrostat to be measured by mUFC levels up to 12 months on patients	up to month 12