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

NCT03708900 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: CLCI699C22032018-001522-25
• Study Type: interventional
• Target: 12
• Locations: 7 countries
• Sites: 15

Brief 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.

Conditions

Cushing Syndrome

Keywords

Cushing's syndrome (CS); LCI699; osilodrostat; Pituitary Gland; Adrenocorticotropic Hormone (ACTH); Urinary Free Cortisol (UFC); mean Urinary Free Cortisol (mUFC)

Outcome Measures

Primary Outcomes (1)

• 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

  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)

  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

  week 3, 6, 9 and week 12 (or end of treatment)

• Extension: Efficacy of osilodrostat as measured by mUFC levels up to Month 12

  up to month 12

• Extension: Efficacy of osilodrostat as measured by mUFC levels up to Month 12

  up to month 12

• assessment of the pharmacodynamics, safety and tolerability of osilodrostat.

  week 3, 6, 9 and week 12 (or end of treatment)

Study Arms (1)

LCI699 (osilodrostat)

EXPERIMENTAL

Subjects with cushing's syndrome taking LCI699 (osilodrostat)

Drug: LCI699

Interventions

LCI699 DRUG

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

Also known as: osilodrostat

LCI699 (osilodrostat)

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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:
• a) 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;
• \. Able to swallow study drug tablets (not crushed or split) or the content of the capsules mixed with water.
• \. Parents or legal guardians able to provide consent/assent.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• RECORDATI GROUP: lead

Study Sites (15)

University of California San Francisco UCSF

San Francisco, California, 94143, United States

RECRUITING

ABMED Clinical Research Corp

Cape Coral, Florida, 33914, United States

RECRUITING

Ann & Robert H. Lurie Children's Hospital

Chicago, Illinois, 60611, United States

RECRUITING

National Institute of Child Health and Human Development

Bethesda, Maryland, 20892, United States

COMPLETED

Texas Valley Clinical Research

Weslaco, Texas, 78596, United States

RECRUITING

UZ Brussel

Jette, Brussels Capital, 1090, Belgium

COMPLETED

Multiprofile Hospital for Active Treatment Sveta Marina EAD

Varna, 9010, Bulgaria

WITHDRAWN

Hospital Necker Enfants Malades

Paris, 75015, France

COMPLETED

Robert Debre Hospital

Paris, 75019, France

COMPLETED

CHU Bicetre APHP Paris Saclay

Paris, 94270, France

COMPLETED

Aziendal Ospedaliero Universitaria Pisana Presidio Ospedale di Cisanello

Pisa, PI, 56124, Italy

COMPLETED

Ospedale Bambino Gesu

Roma, 00165, Italy

COMPLETED

University Clinical Center Ljubljana

Ljubljana, 1525, Slovenia

WITHDRAWN

Alder Hey Childrens NHS Foundation Trust

Liverpool, L12 2AP, United Kingdom

WITHDRAWN

The Royal London Childrens Hospital

London, E11BB, United Kingdom

WITHDRAWN

MeSH Terms

Conditions

Cushing Syndrome; Pituitary Diseases

Interventions

Osilodrostat

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Recordati AG

  Recordati AG

  STUDY DIRECTOR

Central Study Contacts

Recordati

CONTACT

+39 0248787456; casi.m@recordati.it

Recordati

CONTACT

+4161 205 61 00

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2018
• First Posted: October 17, 2018
• Study Start: April 28, 2021
• Primary Completion (Estimated): July 21, 2027
• Study Completion (Estimated): July 21, 2027
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

BU (1); SL (1); BE (1); GB (2); FR (3); US (5); IT (2)