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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Recordati AG

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

Trial duration

21 Sep 2020 → 13 Oct 2025

Decision date (initial)

2024-10-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-516825-30-00

EudraCT number

2018-001522-25

ClinicalTrials.gov

NCT03708900

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Pharmacodynamic, Safety, Pharmacokinetic

To evaluate the pharmacokinetics (PK) of osilodrostat in children and adolescents 6 to <18 years of age with Cushing's Disease

Secondary objectives 1

1. The secondary objectives include assessment of the pharmacodynamics, safety and tolerability of osilodrostat

Conditions and MedDRA coding

Cushing's disease

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000315-PIP02-15

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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

Exclusion criteria 21

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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Pharmacokinetic parameters of osilodrostat

Secondary endpoints 3

1. Proportion of patients with normal mUFC
2. mUFC absolute values and change from baseline
3. Safety and tolerability

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Recordati AG

Sponsor organisation

Recordati AG

Address

Lindenstrasse 8

City

Baar

Postcode

6340

Country

Switzerland

Scientific contact point

Organisation

Recordati AG

Contact name

Gaël Thomas

Public contact point

Organisation

Recordati AG

Contact name

Clinical Trial Information Desk

Third parties 4

Locations

3 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 29 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications