Trial Outcomes & Findings for Roll-over Study in Patients With Endogenous Cushing's Syndrome for LCI699 (NCT NCT03606408)
NCT ID: NCT03606408
Last Updated: 2024-12-18
Results Overview
To evaluate long-term safety data with osilodrostat treatment (Frequency and severity of adverse events (AEs)/serious adverse events (SAEs))
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
127 participants
Primary outcome timeframe
up to 5 years
Results posted on
2024-12-18
Participant Flow
There was no screening period for the study, eligible patients were able to start study treatment as soon as they were enrolled. The study was conducted for 5 years from first patient first visit. Patients continued to be treated in this roll-over study until they no longer received clinical benefit from treatment with osilodrostat (as judged by the Investigator), until osilodrostat was commercially available in their country, or until one of the other discontinuation criteria were met.
The starting dose of this roll-over study was the same as the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the urine cortisol level and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. So it is not feasible to report the results according to the drug dosage and data has been analysed as one arm.
Participant milestones
| Measure |
Osilodrostat
Phase IIb open label, with patients receiving same dose as provided in the parent study
osilodrostat: osilodrostat, in the form of film coated tablets for oral administration, in the following tablet strengths: 1mg, 5mg, 10mg. Each strength has unique tablet size, colour and imprint.
|
|---|---|
|
Overall Study
STARTED
|
127
|
|
Overall Study
COMPLETED
|
99
|
|
Overall Study
NOT COMPLETED
|
28
|
Reasons for withdrawal
| Measure |
Osilodrostat
Phase IIb open label, with patients receiving same dose as provided in the parent study
osilodrostat: osilodrostat, in the form of film coated tablets for oral administration, in the following tablet strengths: 1mg, 5mg, 10mg. Each strength has unique tablet size, colour and imprint.
|
|---|---|
|
Overall Study
Adverse Event
|
13
|
|
Overall Study
Withdrawal by Subject
|
7
|
|
Overall Study
Physician Decision
|
4
|
|
Overall Study
Lack of Efficacy
|
2
|
|
Overall Study
Death
|
1
|
|
Overall Study
new therapy for study indication
|
1
|
Baseline Characteristics
Roll-over Study in Patients With Endogenous Cushing's Syndrome for LCI699
Baseline characteristics by cohort
| Measure |
Osilodrostat
n=127 Participants
Phase IIb open label, with patients receiving same dose as provided in the parent study
osilodrostat: osilodrostat, in the form of film coated tablets for oral administration, in the following tablet strengths: 1mg, 5mg, 10mg. Each strength has unique tablet size, colour and imprint.
|
|---|---|
|
Age, Continuous
|
44.2 years
STANDARD_DEVIATION 12.39 • n=5 Participants
|
|
Age, Customized
<65 years
|
119 Participants
n=5 Participants
|
|
Age, Customized
≥65 years
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
95 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
32 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
14 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
94 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
19 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
26 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
96 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Weight
|
74.59 kg
STANDARD_DEVIATION 21.253 • n=5 Participants
|
|
Height
|
163.73 cm
STANDARD_DEVIATION 9.839 • n=5 Participants
|
|
Body Mass Index
|
27.84 Kg/m^2
STANDARD_DEVIATION 7.631 • n=5 Participants
|
PRIMARY outcome
Timeframe: up to 5 yearsPopulation: The starting dose of this roll-over study was the same as the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the urine cortisol level and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. So, the results are not reported according to the drug dosage and data has been analysed as one arm.
To evaluate long-term safety data with osilodrostat treatment (Frequency and severity of adverse events (AEs)/serious adverse events (SAEs))
Outcome measures
| Measure |
Osilodrostat
n=127 Participants
Phase IIb open label, with patients receiving same dose as provided in the parent study
osilodrostat: osilodrostat, in the form of film coated tablets for oral administration, in the following tablet strengths: 1mg, 5mg, 10mg. Each strength has unique tablet size, colour and imprint.
|
|---|---|
|
Number of Participants With Adverse/Serious Adverse Events
Adverse events (AEs)
|
115 Participants
|
|
Number of Participants With Adverse/Serious Adverse Events
Treatment-related AEs of CTCAE Grade ≥ 3
|
3 Participants
|
|
Number of Participants With Adverse/Serious Adverse Events
Serious adverse events
|
35 Participants
|
|
Number of Participants With Adverse/Serious Adverse Events
Treatment-related SAEs
|
4 Participants
|
|
Number of Participants With Adverse/Serious Adverse Events
Fatal SAEs
|
2 Participants
|
|
Number of Participants With Adverse/Serious Adverse Events
Treatment-related fatal SAEs
|
0 Participants
|
|
Number of Participants With Adverse/Serious Adverse Events
Treatment-related AEs
|
50 Participants
|
|
Number of Participants With Adverse/Serious Adverse Events
Adverse events of CTCAE Grade ≥ 3
|
34 Participants
|
|
Number of Participants With Adverse/Serious Adverse Events
Adverse events leading to discontinuation
|
14 Participants
|
|
Number of Participants With Adverse/Serious Adverse Events
Treatment-related AEs leading to discontinuation
|
5 Participants
|
|
Number of Participants With Adverse/Serious Adverse Events
Adverse events leading to dose interruption or adjustment
|
56 Participants
|
|
Number of Participants With Adverse/Serious Adverse Events
Treatment-related AEs leading to dose interruption or adjustment
|
35 Participants
|
|
Number of Participants With Adverse/Serious Adverse Events
Adverse events requiring additional therapy
|
94 Participants
|
|
Number of Participants With Adverse/Serious Adverse Events
Treatment-related AEs requiring additional therapy
|
17 Participants
|
|
Number of Participants With Adverse/Serious Adverse Events
Adverse events of special interest (AESIs)
|
51 Participants
|
|
Number of Participants With Adverse/Serious Adverse Events
Treatment-related AESIs
|
29 Participants
|
SECONDARY outcome
Timeframe: up to of 5 yearsPopulation: The starting dose of this roll-over study was the same as the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the urine cortisol level and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. So it is not feasible to report the results according to the drug dosage and data has been analysed as one arm.
Proportion of patients with clinical benefit as assessed by the Investigator at scheduled visits based on medical check-up and lab values such as Urine Free Cortisol.
Outcome measures
| Measure |
Osilodrostat
n=127 Participants
Phase IIb open label, with patients receiving same dose as provided in the parent study
osilodrostat: osilodrostat, in the form of film coated tablets for oral administration, in the following tablet strengths: 1mg, 5mg, 10mg. Each strength has unique tablet size, colour and imprint.
|
|---|---|
|
Percentage of Patients With Clinical Benefit
Week 12
|
122 Participants
|
|
Percentage of Patients With Clinical Benefit
Week 24
|
119 Participants
|
|
Percentage of Patients With Clinical Benefit
Week 36
|
114 Participants
|
|
Percentage of Patients With Clinical Benefit
Week 1
|
127 Participants
|
|
Percentage of Patients With Clinical Benefit
Week 48
|
103 Participants
|
|
Percentage of Patients With Clinical Benefit
Week 96
|
74 Participants
|
|
Percentage of Patients With Clinical Benefit
Week 144
|
52 Participants
|
|
Percentage of Patients With Clinical Benefit
End of treatment
|
99 Participants
|
Adverse Events
Osilodrostat
Serious events: 35 serious events
Other events: 115 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Osilodrostat
n=127 participants at risk
Phase IIb open label, with patients receiving same dose as provided in the parent study
osilodrostat: osilodrostat, in the form of film coated tablets for oral administration, in the following tablet strengths: 1mg, 5mg, 10mg. Each strength has unique tablet size, colour and imprint.
|
|---|---|
|
Infections and infestations
COVID-19
|
5.5%
7/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Hepatobiliary disorders
Cholelithiasis
|
2.4%
3/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pitituary tumour
|
2.4%
3/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Endocrine disorders
Adrenal insufficiency
|
1.6%
2/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ACTH-producing pituitary tumour
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Psychiatric disorders
Acute stress disorder
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Investigations
Alanine aminotransferase increased
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Infections and infestations
Appendicitis
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Investigations
Aspartate aminotransferase increased
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Hepatobiliary disorders
Bile duct stone
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Hepatobiliary disorders
Biliary dilatation
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Gastrointestinal disorders
Constipation
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Product Issues
Device dislocation
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
General disorders
Disease progression
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Gastrointestinal disorders
Diverticulitis
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Gastrointestinal disorders
Food poisoning
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Investigations
Gamma-glutamyl transferase increased
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
General disorders
Influenza like illness
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Investigations
Liver function test abnormal
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Gastrointestinal disorders
Nausea
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Nervous system disorders
Paralysis
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pituitary tumour benign
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Endocrine disorders
Pituitary-dependent Cushing's syndrome
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Infections and infestations
Pneumonia
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Infections and infestations
Pneumonia bacterial
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Renal and urinary disorders
Renal colic
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal neoplasm
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Eye disorders
Retinal vein thrombosis
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Renal and urinary disorders
Ureterolithiasis
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
0.79%
1/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
Other adverse events
| Measure |
Osilodrostat
n=127 participants at risk
Phase IIb open label, with patients receiving same dose as provided in the parent study
osilodrostat: osilodrostat, in the form of film coated tablets for oral administration, in the following tablet strengths: 1mg, 5mg, 10mg. Each strength has unique tablet size, colour and imprint.
|
|---|---|
|
Vascular disorders
Hypertension
|
8.7%
11/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Infections and infestations
COVID-19
|
22.8%
29/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Gastrointestinal disorders
Abdominal pain
|
7.1%
9/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Endocrine disorders
Adrenal insufficiency
|
12.6%
16/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Gastrointestinal disorders
Vomiting
|
7.1%
9/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Gastrointestinal disorders
Nausea
|
11.0%
14/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Gastrointestinal disorders
Diarrhoea
|
10.2%
13/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
General disorders
Asthenia
|
7.1%
9/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
General disorders
Fatigue
|
7.1%
9/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
General disorders
Pyrexia
|
6.3%
8/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Infections and infestations
Nasopharyngitis
|
9.4%
12/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Infections and infestations
Influenza
|
8.7%
11/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Infections and infestations
Upper respiratory tract infection
|
7.9%
10/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Infections and infestations
Urinary tract infection
|
5.5%
7/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Investigations
Cortisol free urine increased
|
10.2%
13/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Investigations
SARs-Cov-2 test positive
|
10.2%
13/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
General disorders
Blood corticotrophin increased
|
6.3%
8/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Metabolism and nutrition disorders
Decreased appetite
|
7.1%
9/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.7%
11/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.1%
9/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Nervous system disorders
Headache
|
12.6%
16/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Nervous system disorders
Dizziness
|
7.9%
10/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.5%
7/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.5%
7/127 • From enrolment up to 30 days after the last administration of study treatment (up to 5 years)
The starting dose of this roll-over study was the one the patients were taking at the end of the parent studies. In addition, they underwent to dose adjustment according to the UCF and possible AEs. The daily dosage ranged from 1mg every 3 days to 30mg twice a day. The data has been analysed as one arm. Two patients experienced fatal SAEs before the Safety Follow-up, reported under the PTs of COVID-19 and respiratory failure, not related to the disease or treatment
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place