Patient case (clinical description): A 47-year-old man comes to the office due to weight gain and fatigue.  He is not able to lift heavy objects or climb stairs. Family history is positive for DM type 2 and HTN in his father.  Blood pressure is 165/90 mm Hg and pulse is 85/min.  On physical examination, there is symmetric proximal muscle weakness of the upper and lower extremities.  Fasting plasma glucose level is 138 mg/dL and 24-hour urinary cortisol is twice the upper normal limit.  Further evaluation reveals that high-dose, but not low-dose, dexamethasone suppresses serum cortisol levels.  Serum ACTH levels are high-normal. This patient's findings are consistent with endogenous Cushing Syndrome.

Patient's own account: I'm a 47-year-old man. I went to the clinic because I had been gaining weight and had increased fatigue over the past few weeks. I was not able to lift heavy objects or even climb the stairs. My dad was diagnosed with type 2 diabetes and high blood pressure. During the exam, they took my blood pressure, which was 165/90 mm Hg, and my pulse was 85/min. They found out that I have weaknesses in both of my arms and legs. I also did a blood test on an empty stomach, and I had a glucose level of 138 mg/dL, and twice the upper normal limit of cortisol. I had high-normal levels of ACTH. The doctor said I suffer from endogenous Cushing Syndrome.

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

Eligibility 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.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 6 Years old.
Subject must be at most 18 Years

Eligibility (NLI label): Contradiction