A study of osilodrostat in children and adolescents with Cushing's disease

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 12

Inclusion Criteria

1. Male and female children and adolescents from 6 to < 18 years of age with Cushing’s disease of endogenous origin who have failed surgery or are awaiting surgery or for whom surgery is not an immediate option
2. Body weight greater 30 kg
3. Confirmed diagnosis of Cushing’s disease
4. Able to swallow study drug tablets (not crushed or split)
5. Parents or legal guardians able to provide consent/assent
Are the trial subjects under 18? yes
Number of subjects for this age range: 12
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Macroadenoma complicated by compressive symptoms
2. Insufficient washout period from any other medication used to lower cortisol levels
3. Use of other investigational drugs at the time of enrollment
4. History of hypersensitivity to drugs of the same or similar chemical classes as osilodrostat
5. History of malignancy of any organ system
6. Moderate to severe renal impairment
7. Serum ALT and/or AST > 3 x ULN, or total bilirubin > 1.5 x ULN
8. History of thrombosis
9. 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 (see Section 6.2.2.1)
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, etc.
10. Hypertensive patients with uncontrolled blood pressure
11. Patients who have undergone any major surgery within 1 month
12. Patients who have undergone trans-sphenoidal pituitary surgery within 6 weeks prior to screening, unless they have clear evidence of persistent hypercortisolemia or persistent biochemical changes consistent with Cushing’s disease
13. Use of or anticipated use of systemic glucocorticoid medications 1 month prior to screening.
14. Uncontrolled hypothyroidism as evidenced by Free T4 < 0.8 ng/dl.
15. Uncontrolled hyperthyroidism
16. Diabetic patients with poorly controlled diabetes as evidenced by HbA1c > 8.5 % or not optimally treated for diabetes mellitus as judged by the investigator
17. Positive pregnancy test in females of childbearing potential
18. Female patients of childbearing potential who do not agree to use highly effective birth control methods
19. Pregnant or nursing (lactating) women.
20. 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.
21. Use of concomitant prohibited medications (see section 6.2.2).

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the pharmacokinetics (PK) of osilodrostat in children and adolescents 6 to <18 years of age with Cushing’s Disease;Secondary Objective: The secondary objectives include assessment of the pharmacodynamics, safety and tolerability of osilodrostat;Primary end point(s): Pharmacokinetic parameters of osilodrostat ;Timepoint(s) of evaluation of this end point: up to Week 12

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Proportion of patients with normal mUFC<br>2. mUFC absolute values and change from baseline<br>3. Safety and tolerability;Timepoint(s) of evaluation of this end point: 1. at week 6 and week 12 (or end of treatment)<br>2. up to week 48<br>3. up to week 48