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

• Status: Recruiting
• Trial end date: 2023-11-29
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals

Criteria

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.