Phase 2
N=9
Study of Efficacy and Safety of Osilodrostat in Cushing's Syndrome
Cushing's Syndrome · Ectopic Corticotropin Syndrome · Adrenal Adenoma · Adrenal Carcinoma · AIMAH
Bottom Line
View on ClinicalTrials.gov: NCT02468193 ↗Enrolled (actual)
9
Serious AEs
44.4%
Results posted
Mar 2020
Primary outcome: Primary: Percent Change in the Mean Urine Free Cortisol (mUFC) at the Individual Level at Week 12 — -99.0; -97.8; -94.5; -91.5 percentage change
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Osilodrostat (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Jun 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change in the Mean Urine Free Cortisol (mUFC) at the Individual Level at Week 12 |
-99.0; -97.8; -94.5; -91.5; -81.8; -52.6 | — |
| SECONDARY Percent Change From Baseline in the mUFC at Individual Patient Level at Week 24 (Day 169) and Week 48 (Day 337) |
-99.5; -99.1; -85.2; -91.6; -91.0 | — |
| SECONDARY Absolute Change From Baseline in the mUFC at Week 12 (Day 85), Week 24 (Day 169) and Week 48 (Day 337) |
-422.10; -7428.10; -8521.00 | — |
| SECONDARY Percentage Change From Baseline in the mUFC at Week 12 (Day 85), Week 24 (Day 169) and Week 48 (Day 337) |
-94.47; -91.57; -95.04 | — |
| SECONDARY Percentage of Participants With mUFC Response of Complete, Partial, and Overall Response |
66.7; 11.1; 77.8; 66.7; 33.3; 100 | — |
| SECONDARY Absolute Change From Baseline in Morning Serum Cortisol at Individual Level |
-607; -571; -580; -334; -157; -135 | — |
| SECONDARY Percentage Change From Baseline in Morning Serum Cortisol at Individual Level |
-73.3; -69.0; -70.0; -78.0; -50.8; -43.7 | — |
| SECONDARY Absolute Change From Baseline in ACTH and Other Adrenal Steroid Hormones at Individual Level |
0; 2179; 52; 705; 0; 3601 | — |
| SECONDARY Percentage Change From Baseline in ACTH and Other Adrenal Steroid Hormones at Individual Level |
118.0; 1282; 195.1; 427.3; 24.6; 727.3 | — |
| SECONDARY Absolute Change From Baseline in Other Adrenal Steroid Hormones at Individual Levels |
-4.35; 0.76; -8.5; 0.66; -15.54; -0.03 | — |
| SECONDARY Percentage Change From Baseline in Other Adrenal Steroid Hormones at Individual Levels |
-17.8; 73.1; -34.9; 63.5; -63.7; -2.9 | — |
| SECONDARY Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, Fasting Glucose, at Individual Level |
-0.78; -0.84; -0.78; 1.22; -1.89; 0.22 | — |
| SECONDARY Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, Fasting Glucose, at Individual Level |
-15.3; -16.4; -15.3; 24.2; -27.2; 3.2 | — |
| SECONDARY Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, HbA1c, at Individual Level |
-0.1; -0.1; -0.2; 0.3; -0.4; -0.7 | — |
| SECONDARY Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, HbA1c, at Individual Level |
-1.8; -1.8; -3.6; 6.2; -6.5; -11.3 | — |
| SECONDARY Absolute Change From Baseline in Cardiovascular-related Metabolic Parameters, Cholesterol, HDL Cholesterol, LDL Cholesterol & Triglycerides, at Individual Level |
-0.67; -0.85; 0.21; -0.87; -0.65; -1.01 | — |
| SECONDARY Percentage Change From Baseline in Cardiovascular-related Metabolic Parameters, Cholesterol, HDL Cholesterol, LDL Cholesterol & Triglycerides, at Individual Level |
-11.1; -33.2; 6.3; -49.4; -10.7; -39.5 | — |
| SECONDARY Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, BMI, at Individual Level |
-0.5; -2.3; -1.6; 0.6; -1.2; -3.6 | — |
| SECONDARY Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, BMI, at Individual Level |
-2.1; -9.6; -6.7; 1.9; -3.1; -9.4 | — |
| SECONDARY Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, Waist Circumference, at Individual Level |
-2.0; -7.5; -5.5; -2.0; -1.0; -8.0 | — |
| SECONDARY Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, Waist Circumference, at Individual Level |
-2.4; -9.0; -6.6; -1.8; -0.9; -7.1 | — |
| SECONDARY Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, Sitting Blood Pressure (BP) at Individual Level |
-44.3; -31.0; -48.34; -32.66; -40.34; -19.0 | — |
| SECONDARY Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, Sitting Blood Pressure (BP) at Individual Level |
-31.1; -32.5; -33.9; -34.3; -28.3; -19.9 | — |
| SECONDARY Total Scores in Patient-Reported Outcomes Health-related Quality of Life (QoL) as Assessed by Cushing QoL at Individual Level |
48; 51; 47; 29; 18; 22 | — |
| SECONDARY 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 |
4; 15; 12; 33; 35; 37 | — |
| SECONDARY Plasma Concentrations of Osilodrostat (LCI699) at Week 0 |
0.971; 0.405; 5.11; 5.29; 3.77; 8.12 | — |
| SECONDARY Plasma Concentrations of Osilodrostat (LCI699) at Week 1 |
10.9; 10.5; 21.3; 22.3 | — |
| SECONDARY Plasma Concentrations of Osilodrostat (LCI699) at Week 2 |
3.89; 3.69; 33.1; 34.9; 8.93; 14.3 | — |
| SECONDARY Plasma Concentrations of Osilodrostat (LCI699) at Week 3 |
7.09; 7.62; 23.2; 37.8 | — |
| SECONDARY Plasma Concentrations of Osilodrostat (LCI699) at Week 4 |
4.08; 9.91; 24.0 | — |
| SECONDARY Plasma Concentrations of Osilodrostat (LCI699) at Week 6 |
6.74; 12.7; 31.7 | — |
| SECONDARY Plasma Concentrations of Osilodrostat (LCI699) at Week 8 |
3.35; 13.9 | — |
| SECONDARY Plasma Concentrations of Osilodrostat (LCI699) at Week 10 |
4.73; 11.3 | — |
| SECONDARY Plasma Concentrations of Osilodrostat (LCI699) at Week 12 |
0.382; 3.1; 4.62; 9.98; 3.58; 6.57 | — |
| SECONDARY Plasma Concentrations of Osilodrostat (LCI699) at Week 16 |
5.71 | — |
| SECONDARY Plasma Concentrations of Osilodrostat (LCI699) at Week 20 |
0.794 | — |
| SECONDARY Plasma Concentrations of Osilodrostat (LCI699) at Week 24 |
6.51 | — |
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.
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT02468193). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.