Study of Efficacy and Safety of Osilodrostat in Cushing's Syndrome

Novartis Pharmaceuticals9 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Cushing's Syndrome Ectopic Corticotropin Syndrome Adrenal Adenoma Adrenal Carcinoma AIMAH PPNAD

Interventions

OsilodrostatDRUG

Osirodrostat 1mg, 5mg \& 10mg in the form of film-coated tablets was used for oral administration.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients with confirmed Cushing's syndrome \[i.e. ectopic corticotropin syndrome, adrenal adenoma, adrenal carcinoma, ACTH-Independent Macronodular Adrenal Hyperplasia (AIMAH), or Primary Pigmented Nodular Adrenal Dysplasia (PPNAD)\] * For patients on medical treatment for hypercortisolism due to Cushing's syndrome, the washout periods had to be completed prior to baseline efficacy assessments Exclusion Criteria: * Patients with Cushing's disease * History of hypersensitivity to osilodrostat or to drugs of similar chemical classes * History of malignancy of any organ system, treated or untreated, within the past 5 years * Patients receiving treatment for within 4 weeks or ≤5 x half-life of the agent (whichever is longer) before first dose of osilodrostat * Patients with risk factors for QTc prolongation or Torsade de Pointes

Locations (4)

Novartis Investigative Site

Fukushima, Fukushima, Japan

Novartis Investigative Site

Yokohama, Kanagawa, Japan

Novartis Investigative Site

Sendai, Miyagi, Japan

Novartis Investigative Site

Chiba, Japan

Outcomes

Primary Outcomes

Percent Change in the Mean Urine Free Cortisol (mUFC) at the Individual Level at Week 12

Percent change from baseline in the mUFC at the individual patient level

Time frame: Baseline, 12 weeks

Secondary Outcomes

Percent Change From Baseline in the mUFC at Individual Patient Level at Week 24 (Day 169) and Week 48 (Day 337)

Percent change from baseline in the mUFC at the individual patient level

Time frame: Baseline, Week 24 (day 169) and Week 48 (day 337)

Absolute Change From Baseline in the mUFC at Week 12 (Day 85), Week 24 (Day 169) and Week 48 (Day 337)

Absolute change from baseline in the mUFC