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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02468193
• Date of registration: 08/06/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Study of Efficacy and Safety of Osilodrostat in Cushing's Syndrome
• Scientific title: A Phase II, Open-label, Dose Titration, Multi-center Study to Assess the Safety/Tolerability and Efficacy of Osilodrostat in Patients With All Types of Endogenous Cushing's Syndrome Except Cushing's Disease
• Date of first enrolment: September 24, 2015
• Target sample size: 9
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02468193
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Japan

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

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



Age minimum: 18 Years
Age maximum: 85 Years
Gender: All

Health Condition(s) or Problem(s) studied

Adrenal Adenoma

Adrenal Carcinoma

AIMAH

Cushing's Syndrome

Ectopic Corticotropin Syndrome

PPNAD

Intervention(s)

Drug: Osilodrostat

Primary Outcome(s)

Percent Change in the Mean Urine Free Cortisol (mUFC) at the Individual Level at Week 12 [Time Frame: Baseline, 12 weeks]

Secondary Outcome(s)

Absolute Change From Baseline in ACTH and Other Adrenal Steroid Hormones at Individual Level [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Plasma Concentrations of Osilodrostat (LCI699) at Week 0 [Time Frame: Week 0]

Plasma Concentrations of Osilodrostat (LCI699) at Week 3 [Time Frame: Week 3, 2 hours post-dose]

Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, HbA1c, at Individual Level [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, BMI, at Individual Level [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Percentage Change From Baseline in Other Adrenal Steroid Hormones at Individual Levels [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Percentage Change From Baseline in the mUFC at Week 12 (Day 85), Week 24 (Day 169) and Week 48 (Day 337) [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Absolute Change From Baseline in Other Adrenal Steroid Hormones at Individual Levels [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Total Scores in Patient-Reported Outcomes Health-related Quality of Life (QoL) as Assessed by Beck Depression Inventory II (BDI-ll) Depression Score at Individual Level [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Percent Change From Baseline in the mUFC at Individual Patient Level at Week 24 (Day 169) and Week 48 (Day 337) [Time Frame: Baseline, Week 24 (day 169) and Week 48 (day 337)]

Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, BMI, at Individual Level [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, Sitting Blood Pressure (BP) at Individual Level [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, Fasting Glucose, at Individual Level [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, HbA1c, at Individual Level [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, Sitting Blood Pressure (BP) at Individual Level [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Plasma Concentrations of Osilodrostat (LCI699) at Week 10 [Time Frame: Week 10, 2 hours post-dose]

Percentage Change From Baseline in ACTH and Other Adrenal Steroid Hormones at Individual Level [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, Fasting Glucose, at Individual Level [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, Waist Circumference, at Individual Level [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Percentage Change From Baseline in Morning Serum Cortisol at Individual Level [Time Frame: Baseline, Week 12 (day 85), 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) [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Plasma Concentrations of Osilodrostat (LCI699) at Week 1 [Time Frame: Week 1, 2 hours post-dose]

Plasma Concentrations of Osilodrostat (LCI699) at Week 24 [Time Frame: Week 24, 2 hours post-dose]

Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, Waist Circumference, at Individual Level [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Plasma Concentrations of Osilodrostat (LCI699) at Week 2 [Time Frame: Week 2]

Plasma Concentrations of Osilodrostat (LCI699) at Week 6 [Time Frame: Week 6, 2 hours post-dose]

Percentage Change From Baseline in Cardiovascular-related Metabolic Parameters, Cholesterol, HDL Cholesterol, LDL Cholesterol & Triglycerides, at Individual Level [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Percentage of Participants With mUFC Response of Complete, Partial, and Overall Response [Time Frame: 12, 24 and 48 weeks]

Plasma Concentrations of Osilodrostat (LCI699) at Week 16 [Time Frame: Week 16, 2 hours post-dose]

Absolute Change From Baseline in Cardiovascular-related Metabolic Parameters, Cholesterol, HDL Cholesterol, LDL Cholesterol & Triglycerides, at Individual Level [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Absolute Change From Baseline in Morning Serum Cortisol at Individual Level [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Plasma Concentrations of Osilodrostat (LCI699) at Week 12 [Time Frame: Week 12]

Plasma Concentrations of Osilodrostat (LCI699) at Week 20 [Time Frame: Week 20, 2 hours post-dose]

Plasma Concentrations of Osilodrostat (LCI699) at Week 4 [Time Frame: Week 4, 2 hours post-dose]

Total Scores in Patient-Reported Outcomes Health-related Quality of Life (QoL) as Assessed by Cushing QoL at Individual Level [Time Frame: Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

Plasma Concentrations of Osilodrostat (LCI699) at Week 8 [Time Frame: Week 8, 2 hours post-dose]

Secondary ID(s)

CLCI699C1201

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 11/03/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02468193