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

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

Multicenter, open-label, non-comparative study to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of osilodrostat in children and adolescent patients with Cushing's disease.

Study Overview

• Status: Recruiting
• Conditions: Cushing's Disease
• Intervention / Treatment: Drug: LCI699

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 Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Recordati; Phone Number: +390248787456; Email: casi.m@recordati.it
• Study Contact Backup: Name: Recordati; Phone Number: +4161 205 61 00

Study Locations

• Belgium
  • Brussel
    • Jette, Brussel, Belgium, 1090
      • Recruiting
      • Recordati Investigative Site
• Bulgaria
  • Varna, Bulgaria, 9010
    • Recruiting
    • Recordati Investigative Site
• Italy
  • Roma, Italy, 00165
    • Recruiting
    • Recordati Investigative Site
  • PI
    • Pisa, PI, Italy, 56124
      • Recruiting
      • Recordati Investigative Site
• Slovenia
  • Ljubljana, Slovenia, 1525
    • Recruiting
    • Recordati Investigative Site
• United Kingdom
  • Liverpool, United Kingdom, L12 2AP
    • Not yet recruiting
    • Recordati Investigative Site
  • London, United Kingdom, E11BB
    • Recruiting
    • Recordati Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LCI699 (osilodrostat); Subjects with cushing's disease taking LCI699 (osilodrostat)	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.; Other Names: osilodrostat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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
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

Collaborators and Investigators

• Sponsor: RECORDATI GROUP
• Investigators: Study Director: Recordati AG, Recordati AG

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 28, 2021
• Primary Completion (ANTICIPATED): February 21, 2023
• Study Completion (ANTICIPATED): November 29, 2023

Study Registration Dates

• First Submitted: October 8, 2018
• First Submitted That Met QC Criteria: October 15, 2018
• First Posted (ACTUAL): October 17, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 6, 2022
• Last Update Submitted That Met QC Criteria: May 2, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: osilodrostat; LCI699; Pituitary Gland; Cushing's disease (CD); Adrenocorticotropic Hormone (ACTH); Urinary Free Cortisol (UFC); mean Urinary Free Cortisol (mUFC)
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Hypothalamic Diseases; Hyperpituitarism; Pituitary Diseases; Adenoma; Pituitary Neoplasms; ACTH-Secreting Pituitary Adenoma; Pituitary ACTH Hypersecretion
• Other Study ID Numbers: CLCI699C2203; 2018-001522-25 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No