Study of Efficacy and Safety of Osilodrostat in Cushing's Syndrome
Condition: Cushing's Syndrome; Ectopic Corticotropin Syndrome; Adrenal Adenoma; Adrenal Carcinoma; AIMAH; PPNAD
MeSH terms: Adenoma; Adrenocortical Adenoma; Adrenocortical Carcinoma; ACTH Syndrome, Ectopic; Cushing Syndrome; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      The study aim was to investigate the efficacy and safety of Osilodrostat in patients with
      Cushing's syndrome due to causes other than Cushing's disease in Japan.
    

Detailed description: 
      This was a Phase II, single arm, open-label, dose titration, multi-center study which
      consisted of two distinct Study Periods plus an optional extension period in non-CD patients
      with CS. The 3 Study Periods (two distinct Study Periods plus an optional extension period)
      were as follows:

      Study Period I [Week 0 (Day 1) to Week-12]: Study Period I was the dose titration period to
      achieve a stable therapeutic dose and to assess the efficacy and safety of osilodrostat.

      The dosing regimen of osilodrostat in this study was titrated according to the following
      escalation sequence: osilodrostat 2 mg bid, 5 mg bid, 10 mg bid, 20 mg bid, and 30 mg bid.
      Dose adjustments were based on the serum cortisol values measured by the local lab at each
      site. Osilodrostat titration was done weekly for the initial 4-weeks, up to a maximum dose of
      10 mg bid.

      The mean of three 24-hour UFC (mUFC) values were measured to evaluate the efficacy in this
      period.

      Study Period II (After Week-12 to Week-48): Study Period II was the period to assess the
      sustainability of efficacy and long term safety.

      During Study Period II, only patients who tolerated and agreed to continue osilodrostat
      treatment continued on the study. The patient was administered with the stable therapeutic
      dose which was achieved in the Study Period I.

      Optional extension period (After Week-48): Patients who continued to receive clinical
      benefit, as assessed by the study Investigator and who wished to enter the extension period
      were reconsented at Week-48. Patients who entered the extension period continued to be
      treated with the study drug without interruption to be assessed for efficacy and safety.
      Patients who continued to benefit from study treatment as assessed by the study investigator
      and who completed Week-72 were offered to participate in a separate long-term safety
      follow-up study. The optional extension period ended after all patients had completed Week-72
      or had discontinued early.

      Post-treatment Follow-up: All patients had 30 days safety follow-up after the last dose of
      study treatment.
    

Intervention name(s): Osilodrostat
Intervention type(s): Drug
Intervention description(s): Osirodrostat 1mg, 5mg & 10mg in the form of film-coated tablets was used for oral administration.
Other intervention name(s): LCI699
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Cushing's syndrome; osilodrostat; LCI699; ectopic corticotropin syndrome; adrenal adenoma; adrenal carcinoma; ACTH-Independent Macronodular Adrenal Hyperplasia; AIMAH; Primary Pigmented Nodular Adrenal Dysplasia; PPNAD