Cushing's Syndrome
Conditions
Keywords
Cushing's syndrome, osilodrostat, LCI699, endogenous Cushing's syndrome
Brief summary
The purpose of this study is the evaluation of long-term safety of osilodrostat in patients who have already received osilodrostat treatment in a previous Global Novartis-sponsored trial and who, based on investigators' judgement, will continue benefiting with its administration.
Detailed description
There will be no screening period for this study. Eligible subjects can start their treatment with osilodrostat as soon as they are enrolled in the study. The first study visit will be scheduled at the time of the last study visit for the parent study. Subjects must return to the study center at least on a quarterly basis (every 12 weeks ± 2 weeks) for safety and clinical benefit assessments, and resupply of study medication. Drug dispensing and administration information and adverse events will be collected. The subject may return to the clinic at any given time as per standard of care or treating physician recommendation; however, only the quarterly study visits will be recorded in the Case Report Form (CRF). Study medication dispensed will be recorded in the CRF dose administration page. All adverse events and serious adverse events, including pregnancy, will be collected throughout the study. Subjects will continue to be treated in this roll-over study until they are no longer benefiting from their osilodrostat treatment as judged by the Investigator or until osilodrostat is commercially available or until one of other discontinuation criteria is met.
Interventions
DRUGosilodrostat
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.
Sponsors
RECORDATI GROUP
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patient is currently participating in a Global Novartis-sponsored study receiving osilodrostat for any type of endogenous CS and has fulfilled all their requirements in the parent study. * Patient is currently benefiting from treatment with osilodrostat, as determined by the Investigator. * Patient has demonstrated compliance, as assessed by the Investigator, with the parent study protocol requirements. * Willingness and ability to comply with scheduled visits and treatment plans. * Written informed consent obtained prior to enrolling into the roll-over study before evaluating the applicability of the subject's participating in the study. -- If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
Exclusion criteria
* Patient has been permanently discontinued from osilodrostat study treatment in a parent Novartis-sponsor study. * Patients who are receiving osilodrostat in combination with unapproved or experimental treatments for any type of endogenous CS. * Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test. Pregnant or nursing (lactating) women * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 1 week of study after stopping medication. Highly effective contraception methods include: * Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception * Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation. at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment * Male sterilization (at least 6 months prior to baseline). The vasectomized male partner should be the sole partner for that subject * Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse/Serious Adverse Events | up to 5 years | To evaluate long-term safety data with osilodrostat treatment (Frequency and severity of adverse events (AEs)/serious adverse events (SAEs)) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Clinical Benefit | up to of 5 years | 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. |
Countries
Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, China, Costa Rica, France, Germany, India, Italy, Japan, Netherlands, Poland, Russia, South Korea, Spain, Thailand, Turkey (Türkiye), United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 127 |
| Total | 127 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 13 |
| Overall Study | Death | 1 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | new therapy for study indication | 1 |
| Overall Study | Physician Decision | 4 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | Osilodrostat |
|---|---|
| Age, Continuous | 44.2 years STANDARD_DEVIATION 12.39 |
| Age, Customized <65 years | 119 Participants |
| Age, Customized ≥65 years | 8 Participants |
| Body Mass Index | 27.84 Kg/m^2 STANDARD_DEVIATION 7.631 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 94 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 19 Participants |
| Height | 163.73 cm STANDARD_DEVIATION 9.839 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 26 Participants |
| Race (NIH/OMB) Black or African American | 4 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 | 1 Participants |
| Race (NIH/OMB) White | 96 Participants |
| Sex: Female, Male Female | 95 Participants |
| Sex: Female, Male Male | 32 Participants |
| Weight | 74.59 kg STANDARD_DEVIATION 21.253 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 127 |
| other Total, other adverse events | 115 / 127 |
| serious Total, serious adverse events | 35 / 127 |
Outcome results
Primary
Number of Participants With Adverse/Serious Adverse Events
To evaluate long-term safety data with osilodrostat treatment (Frequency and severity of adverse events (AEs)/serious adverse events (SAEs))
Time frame: up to 5 years
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Osilodrostat | Number of Participants With Adverse/Serious Adverse Events | Adverse events (AEs) | 115 Participants |
| Osilodrostat | Number of Participants With Adverse/Serious Adverse Events | Treatment-related AEs | 50 Participants |
| Osilodrostat | Number of Participants With Adverse/Serious Adverse Events | Adverse events of CTCAE Grade ≥ 3 | 34 Participants |
| Osilodrostat | Number of Participants With Adverse/Serious Adverse Events | Adverse events leading to discontinuation | 14 Participants |
| Osilodrostat | Number of Participants With Adverse/Serious Adverse Events | Treatment-related AEs leading to discontinuation | 5 Participants |
| Osilodrostat | Number of Participants With Adverse/Serious Adverse Events | Adverse events leading to dose interruption or adjustment | 56 Participants |
| Osilodrostat | Number of Participants With Adverse/Serious Adverse Events | Treatment-related AEs leading to dose interruption or adjustment | 35 Participants |
| Osilodrostat | Number of Participants With Adverse/Serious Adverse Events | Treatment-related AEs of CTCAE Grade ≥ 3 | 3 Participants |
| Osilodrostat | Number of Participants With Adverse/Serious Adverse Events | Serious adverse events | 35 Participants |
| Osilodrostat | Number of Participants With Adverse/Serious Adverse Events | Treatment-related SAEs | 4 Participants |
| Osilodrostat | Number of Participants With Adverse/Serious Adverse Events | Fatal SAEs | 2 Participants |
| Osilodrostat | Number of Participants With Adverse/Serious Adverse Events | Treatment-related fatal SAEs | 0 Participants |
| Osilodrostat | Number of Participants With Adverse/Serious Adverse Events | Adverse events requiring additional therapy | 94 Participants |
| Osilodrostat | Number of Participants With Adverse/Serious Adverse Events | Treatment-related AEs requiring additional therapy | 17 Participants |
| Osilodrostat | Number of Participants With Adverse/Serious Adverse Events | Adverse events of special interest (AESIs) | 51 Participants |
| Osilodrostat | Number of Participants With Adverse/Serious Adverse Events | Treatment-related AESIs | 29 Participants |
Secondary
Percentage of Patients With Clinical Benefit
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.
Time frame: up to of 5 years
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Osilodrostat | Percentage of Patients With Clinical Benefit | Week 96 | 74 Participants |
| Osilodrostat | Percentage of Patients With Clinical Benefit | Week 144 | 52 Participants |
| Osilodrostat | Percentage of Patients With Clinical Benefit | Week 1 | 127 Participants |
| Osilodrostat | Percentage of Patients With Clinical Benefit | Week 12 | 122 Participants |
| Osilodrostat | Percentage of Patients With Clinical Benefit | Week 24 | 119 Participants |
| Osilodrostat | Percentage of Patients With Clinical Benefit | Week 36 | 114 Participants |
| Osilodrostat | Percentage of Patients With Clinical Benefit | Week 48 | 103 Participants |
| Osilodrostat | Percentage of Patients With Clinical Benefit | End of treatment | 99 Participants |