Cushing's Syndrome
Conditions
Keywords
Endogenous Cushing's Syndrome, Cushing's Syndrome, Osilodrostat
Brief summary
This is a multi-centre, observational, non-comparative, retrospective cohort study designed to evaluate the long-term safety and effectiveness of osilodrostat in non-CD CS patients. Patients treated with oral osilodrostat regardless of the duration of their treatment will be followed retrospectively for up to 36 months after initiating osilodrostat.
Interventions
DRUGOsilodrostat
oral administration
Sponsors
RECORDATI GROUP
Study design
Observational model
OTHER
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male and female patients ≥18 years old with diagnosis of CS, except for CD (i.e., an aetiology of adrenal adenoma, adrenocortical carcinoma, adrenal hyperplasia, or ectopic adrenocorticotropic hormone secretion). Patients should have a contemporaneously documented diagnosis of CS as per effective guidelines. 2. Patients treated with osilodrostat between April 2019 and study start date as part of ATU programme or commercialisation.
Exclusion criteria
1. Patients who participated in a clinical trial anytime during the study period. 2. Patients with Pseudo-Cushing's syndrome, cyclic CS, or iatrogenic CS.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effectiveness of Osilodrostat | at week 12 | Number and proportion of patients with Mean Urinary Free Cortisol (mUFC) ≤ upper limit of normal (ULN) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Long-term Effects of Osilodrostat on Mean Urinary Free Cortisol (mUFC) | at weeks 18, 24, 36, 48, 60, and 72 | Proportion of patients with Mean Urinary Free Cortisol (mUFC) ≤ upper limit of normal (ULN) by visit until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. |
| Long Term Effects of Osilodrostat on Morning Serum Cortisol | At baseline and Weeks 4, 8, 12, 18, 24, 36, 48, 60 and 72 | Proportion of patients with normal measures of morning serum cortisol \[≤ upper normal limit (ULN)\] by visit until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. |
| Long-term Effects of Osilodrostat on Composite Cortisol Measure | At baseline and Weeks 4, 8, 12, 18, 24, 36, 48, 60 and 72 | Proportion of patients with normal response of composite cortisol (salivary cortisol, urinary cortisol and morning serum cortisol) \[≤ upper normal limit (ULN)\] by visit until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Osilodrostat Patients treated with oral osilodrostat regardless of the duration of their treatment followed retrospectively for up to 36 months after initiating osilodrostat. Followup of each patient was variable and based on the clinical judgement od the physicians | 103 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Death | 30 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Osilodrostat discontinued | 4 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Planned surgery related to Cushing Syndrome (CS) | 15 |
| Overall Study | Progressive disease | 2 |
Baseline characteristics
| Characteristic | Osilodrostat |
|---|---|
| Age, Continuous | 59.3 years STANDARD_DEVIATION 15.52 |
| Age, Customized ≤ 65 years | 58 Participants |
| Age, Customized ≥ 65 years | 45 Participants |
| BMI | 27.77 kg/m^2 STANDARD_DEVIATION 6.937 |
| CS causation Adrenal Adenoma | 17 Participants |
| CS causation Adrenal hyperplasia | 14 Participants |
| CS causation Adrenocortical carcinoma | 19 Participants |
| CS causation Ectopic ACTH secretion | 53 Participants |
| Duration since CS diagnosis | 14.27 Months STANDARD_DEVIATION 38.619 |
| Height | 166.7 cm STANDARD_DEVIATION 10.57 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 103 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 63 Participants |
| Sex: Female, Male Male | 40 Participants |
| Weight | 76.55 kg STANDARD_DEVIATION 22.295 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 30 / 103 |
| other Total, other adverse events | 87 / 103 |
| serious Total, serious adverse events | 52 / 103 |
Outcome results
Primary
Effectiveness of Osilodrostat
Number and proportion of patients with Mean Urinary Free Cortisol (mUFC) ≤ upper limit of normal (ULN)
Time frame: at week 12
Population: Patients demonstrating a complete mUFC response at Week 12 with non-missing values
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Osilodrostat_ITT | Effectiveness of Osilodrostat | 23 Participants |
Secondary
Long-term Effects of Osilodrostat on Composite Cortisol Measure
Proportion of patients with normal response of composite cortisol (salivary cortisol, urinary cortisol and morning serum cortisol) \[≤ upper normal limit (ULN)\] by visit until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up.
Time frame: At baseline and Weeks 4, 8, 12, 18, 24, 36, 48, 60 and 72
Population: Only the subjects with no-missing data at each visit were considered in the analysis
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Osilodrostat_ITT | Long-term Effects of Osilodrostat on Composite Cortisol Measure | week 60 | 13 Participants |
| Osilodrostat_ITT | Long-term Effects of Osilodrostat on Composite Cortisol Measure | Baseline | 30 Participants |
| Osilodrostat_ITT | Long-term Effects of Osilodrostat on Composite Cortisol Measure | week 4 | 30 Participants |
| Osilodrostat_ITT | Long-term Effects of Osilodrostat on Composite Cortisol Measure | week 8 | 11 Participants |
| Osilodrostat_ITT | Long-term Effects of Osilodrostat on Composite Cortisol Measure | week 12 | 35 Participants |
| Osilodrostat_ITT | Long-term Effects of Osilodrostat on Composite Cortisol Measure | week 18 | 16 Participants |
| Osilodrostat_ITT | Long-term Effects of Osilodrostat on Composite Cortisol Measure | week 24 | 23 Participants |
| Osilodrostat_ITT | Long-term Effects of Osilodrostat on Composite Cortisol Measure | week 36 | 13 Participants |
| Osilodrostat_ITT | Long-term Effects of Osilodrostat on Composite Cortisol Measure | week 48 | 10 Participants |
| Osilodrostat_ITT | Long-term Effects of Osilodrostat on Composite Cortisol Measure | week 72 | 8 Participants |
Secondary
Long-term Effects of Osilodrostat on Mean Urinary Free Cortisol (mUFC)
Proportion of patients with Mean Urinary Free Cortisol (mUFC) ≤ upper limit of normal (ULN) by visit until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up.
Time frame: at weeks 18, 24, 36, 48, 60, and 72
Population: Of all the patients, only the ones with non missing data at each visit were considered to analyse the variation on mUFC
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Osilodrostat_ITT | Long-term Effects of Osilodrostat on Mean Urinary Free Cortisol (mUFC) | week 18 | 7 Participants |
| Osilodrostat_ITT | Long-term Effects of Osilodrostat on Mean Urinary Free Cortisol (mUFC) | week 24 | 12 Participants |
| Osilodrostat_ITT | Long-term Effects of Osilodrostat on Mean Urinary Free Cortisol (mUFC) | week 36 | 6 Participants |
| Osilodrostat_ITT | Long-term Effects of Osilodrostat on Mean Urinary Free Cortisol (mUFC) | week 48 | 6 Participants |
| Osilodrostat_ITT | Long-term Effects of Osilodrostat on Mean Urinary Free Cortisol (mUFC) | week 60 | 6 Participants |
| Osilodrostat_ITT | Long-term Effects of Osilodrostat on Mean Urinary Free Cortisol (mUFC) | week 72 | 6 Participants |
Secondary
Long Term Effects of Osilodrostat on Morning Serum Cortisol
Proportion of patients with normal measures of morning serum cortisol \[≤ upper normal limit (ULN)\] by visit until the earlier of loss to follow-up, treatment discontinuation, death and up to 36 months of retrospective follow-up.
Time frame: At baseline and Weeks 4, 8, 12, 18, 24, 36, 48, 60 and 72
Population: The analysis was done only on patients with no-missing data at each visit
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Osilodrostat_ITT | Long Term Effects of Osilodrostat on Morning Serum Cortisol | Baseline | 18 Participants |
| Osilodrostat_ITT | Long Term Effects of Osilodrostat on Morning Serum Cortisol | week 4 | 19 Participants |
| Osilodrostat_ITT | Long Term Effects of Osilodrostat on Morning Serum Cortisol | week 8 | 6 Participants |
| Osilodrostat_ITT | Long Term Effects of Osilodrostat on Morning Serum Cortisol | week 12 | 22 Participants |
| Osilodrostat_ITT | Long Term Effects of Osilodrostat on Morning Serum Cortisol | week 18 | 10 Participants |
| Osilodrostat_ITT | Long Term Effects of Osilodrostat on Morning Serum Cortisol | week 24 | 16 Participants |
| Osilodrostat_ITT | Long Term Effects of Osilodrostat on Morning Serum Cortisol | week 36 | 8 Participants |
| Osilodrostat_ITT | Long Term Effects of Osilodrostat on Morning Serum Cortisol | week 48 | 9 Participants |
| Osilodrostat_ITT | Long Term Effects of Osilodrostat on Morning Serum Cortisol | week 60 | 9 Participants |
| Osilodrostat_ITT | Long Term Effects of Osilodrostat on Morning Serum Cortisol | week 72 | 6 Participants |