Trial Outcomes & Findings for Osilodrostat for the Treatment of Non-Cushing's Disease Cushing's Syndrome (NCT NCT05633953)
NCT ID: NCT05633953
Last Updated: 2025-02-10
Results Overview
Number and proportion of patients with Mean Urinary Free Cortisol (mUFC) ≤ upper limit of normal (ULN)
Recruitment status
COMPLETED
Target enrollment
103 participants
Primary outcome timeframe
at week 12
Results posted on
2025-02-10
Participant Flow
Participant milestones
| Measure |
Osilodrostat
Patients treated with oral osilodrostat regardless of the duration of their treatment or dosage 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
|
|---|---|
|
Overall Study
STARTED
|
103
|
|
Overall Study
COMPLETED
|
43
|
|
Overall Study
NOT COMPLETED
|
60
|
Reasons for withdrawal
| Measure |
Osilodrostat
Patients treated with oral osilodrostat regardless of the duration of their treatment or dosage 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
|
|---|---|
|
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
Unable to collect for some patients
Baseline characteristics by cohort
| Measure |
Osilodrostat
n=103 Participants
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
|
|---|---|
|
Age, Continuous
|
59.3 years
STANDARD_DEVIATION 15.52 • n=103 Participants
|
|
Age, Customized
≤ 65 years
|
58 Participants
n=103 Participants
|
|
Age, Customized
≥ 65 years
|
45 Participants
n=103 Participants
|
|
Sex: Female, Male
Female
|
63 Participants
n=103 Participants
|
|
Sex: Female, Male
Male
|
40 Participants
n=103 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=103 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=103 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=103 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=103 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=103 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=103 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
103 Participants
n=103 Participants
|
|
Height
|
166.7 cm
STANDARD_DEVIATION 10.57 • n=99 Participants • Unable to collect for some patients
|
|
Weight
|
76.55 kg
STANDARD_DEVIATION 22.295 • n=88 Participants • Unable to collect data for some partecipants
|
|
BMI
|
27.77 kg/m^2
STANDARD_DEVIATION 6.937 • n=86 Participants • Unable to collect data from some partecipants
|
|
Duration since CS diagnosis
|
14.27 Months
STANDARD_DEVIATION 38.619 • n=103 Participants
|
|
CS causation
Adrenal Adenoma
|
17 Participants
n=103 Participants
|
|
CS causation
Adrenocortical carcinoma
|
19 Participants
n=103 Participants
|
|
CS causation
Adrenal hyperplasia
|
14 Participants
n=103 Participants
|
|
CS causation
Ectopic ACTH secretion
|
53 Participants
n=103 Participants
|
PRIMARY outcome
Timeframe: at week 12Population: Patients demonstrating a complete mUFC response at Week 12 with non-missing values
Number and proportion of patients with Mean Urinary Free Cortisol (mUFC) ≤ upper limit of normal (ULN)
Outcome measures
| Measure |
Osilodrostat_ITT
n=45 Participants
Patients treated with oral osilodrostat regardless of the duration of their treatment followed retrospectively for up to 36 months after initiating osilodrostat.
Intent-to-treat (ITT) Population: All enrolled patients who had met all inclusion criteria and none of the exclusion criteria and received osilodrostat treatment for non-CD CS, with a potential follow-up of at least 12 weeks.
|
|---|---|
|
Effectiveness of Osilodrostat
|
23 Participants
|
SECONDARY outcome
Timeframe: at weeks 18, 24, 36, 48, 60, and 72Population: Of all the patients, only the ones with non missing data at each visit were considered to analyse the variation on 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.
Outcome measures
| Measure |
Osilodrostat_ITT
n=21 Participants
Patients treated with oral osilodrostat regardless of the duration of their treatment followed retrospectively for up to 36 months after initiating osilodrostat.
Intent-to-treat (ITT) Population: All enrolled patients who had met all inclusion criteria and none of the exclusion criteria and received osilodrostat treatment for non-CD CS, with a potential follow-up of at least 12 weeks.
|
|---|---|
|
Long-term Effects of Osilodrostat on Mean Urinary Free Cortisol (mUFC)
week 18
|
7 Participants
|
|
Long-term Effects of Osilodrostat on Mean Urinary Free Cortisol (mUFC)
week 24
|
12 Participants
|
|
Long-term Effects of Osilodrostat on Mean Urinary Free Cortisol (mUFC)
week 36
|
6 Participants
|
|
Long-term Effects of Osilodrostat on Mean Urinary Free Cortisol (mUFC)
week 48
|
6 Participants
|
|
Long-term Effects of Osilodrostat on Mean Urinary Free Cortisol (mUFC)
week 60
|
6 Participants
|
|
Long-term Effects of Osilodrostat on Mean Urinary Free Cortisol (mUFC)
week 72
|
6 Participants
|
SECONDARY outcome
Timeframe: At baseline and Weeks 4, 8, 12, 18, 24, 36, 48, 60 and 72Population: The analysis was done only on patients with no-missing data at each visit
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.
Outcome measures
| Measure |
Osilodrostat_ITT
n=56 Participants
Patients treated with oral osilodrostat regardless of the duration of their treatment followed retrospectively for up to 36 months after initiating osilodrostat.
Intent-to-treat (ITT) Population: All enrolled patients who had met all inclusion criteria and none of the exclusion criteria and received osilodrostat treatment for non-CD CS, with a potential follow-up of at least 12 weeks.
|
|---|---|
|
Long Term Effects of Osilodrostat on Morning Serum Cortisol
Baseline
|
18 Participants
|
|
Long Term Effects of Osilodrostat on Morning Serum Cortisol
week 4
|
19 Participants
|
|
Long Term Effects of Osilodrostat on Morning Serum Cortisol
week 8
|
6 Participants
|
|
Long Term Effects of Osilodrostat on Morning Serum Cortisol
week 12
|
22 Participants
|
|
Long Term Effects of Osilodrostat on Morning Serum Cortisol
week 18
|
10 Participants
|
|
Long Term Effects of Osilodrostat on Morning Serum Cortisol
week 24
|
16 Participants
|
|
Long Term Effects of Osilodrostat on Morning Serum Cortisol
week 36
|
8 Participants
|
|
Long Term Effects of Osilodrostat on Morning Serum Cortisol
week 48
|
9 Participants
|
|
Long Term Effects of Osilodrostat on Morning Serum Cortisol
week 60
|
9 Participants
|
|
Long Term Effects of Osilodrostat on Morning Serum Cortisol
week 72
|
6 Participants
|
SECONDARY outcome
Timeframe: At baseline and Weeks 4, 8, 12, 18, 24, 36, 48, 60 and 72Population: Only the subjects with no-missing data at each visit were considered in the analysis
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.
Outcome measures
| Measure |
Osilodrostat_ITT
n=68 Participants
Patients treated with oral osilodrostat regardless of the duration of their treatment followed retrospectively for up to 36 months after initiating osilodrostat.
Intent-to-treat (ITT) Population: All enrolled patients who had met all inclusion criteria and none of the exclusion criteria and received osilodrostat treatment for non-CD CS, with a potential follow-up of at least 12 weeks.
|
|---|---|
|
Long-term Effects of Osilodrostat on Composite Cortisol Measure
week 24
|
23 Participants
|
|
Long-term Effects of Osilodrostat on Composite Cortisol Measure
week 18
|
16 Participants
|
|
Long-term Effects of Osilodrostat on Composite Cortisol Measure
week 36
|
13 Participants
|
|
Long-term Effects of Osilodrostat on Composite Cortisol Measure
week 48
|
10 Participants
|
|
Long-term Effects of Osilodrostat on Composite Cortisol Measure
Baseline
|
30 Participants
|
|
Long-term Effects of Osilodrostat on Composite Cortisol Measure
week 4
|
30 Participants
|
|
Long-term Effects of Osilodrostat on Composite Cortisol Measure
week 8
|
11 Participants
|
|
Long-term Effects of Osilodrostat on Composite Cortisol Measure
week 12
|
35 Participants
|
|
Long-term Effects of Osilodrostat on Composite Cortisol Measure
week 60
|
13 Participants
|
|
Long-term Effects of Osilodrostat on Composite Cortisol Measure
week 72
|
8 Participants
|
Adverse Events
Osilodrostat
Serious events: 52 serious events
Other events: 87 other events
Deaths: 30 deaths
Serious adverse events
| Measure |
Osilodrostat
n=103 participants at risk
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
|
|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroendocrine carcinoma
|
2.9%
3/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
1.9%
2/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Endocrine disorders
Adrenal insufficiency
|
9.7%
10/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
General disorders
General physical health deterioration
|
4.9%
5/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
General disorders
Death
|
2.9%
3/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
General disorders
Multi organ dynsfunction syndrome
|
1.9%
2/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Gastrointestinal disorders
Abdominal Pain
|
2.9%
3/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
2.9%
3/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
1.9%
2/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Nervous system disorders
Presyncope
|
2.9%
3/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Nervous system disorders
Epilepsy
|
1.9%
2/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Cardiac disorders
Cardiac failure acute
|
1.9%
2/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Cardiac disorders
Cardio-respiratory arrest
|
1.9%
2/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Infections and infestations
COVID-19
|
1.9%
2/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Renal and urinary disorders
Acute kidney injury
|
5.8%
6/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
1.9%
2/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Vascular disorders
Vascular disorders
|
3.9%
4/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Blood and lymphatic system disorders
Anemia
|
1.9%
2/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Ear and labyrinth disorders
Ear and labyrinth disorders
|
0.97%
1/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Hepatobiliary disorders
Hepatobiliary disorders
|
0.97%
1/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications
|
0.97%
1/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Reproductive system and breast disorders
Reproductive system and breast disorders
|
0.97%
1/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
Other adverse events
| Measure |
Osilodrostat
n=103 participants at risk
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
|
|---|---|
|
General disorders
Asthenia
|
13.6%
14/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
General disorders
Oedema peripheral
|
5.8%
6/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Endocrine disorders
Adrenal insufficiency
|
28.2%
29/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Gastrointestinal disorders
Diarrhoea
|
12.6%
13/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Gastrointestinal disorders
Nausea
|
11.7%
12/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Gastrointestinal disorders
Abdominal pain
|
6.8%
7/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Gastrointestinal disorders
Constipation
|
5.8%
6/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
17.5%
18/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Renal and urinary disorders
Acute kidney injury
|
7.8%
8/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Vascular disorders
Hypertension
|
5.8%
6/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
|
Blood and lymphatic system disorders
Anaemia
|
5.8%
6/103 • For 36 months (study period) and for at least 12 weeks of retrospective follow-up (follow-up for each patient was variable, and based on the clinical judgement of the physicians at the investigative sites).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place