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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| osilodrostat | Other | open label, with patients receiving same dose as provided in the parent study |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| osilodrostat | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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)) | up to 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | up to of 5 years |
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Inclusion Criteria:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Recordati | Recordati AG | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado | Aurora | Colorado | 80045 | United States | ||
| Emory University School of Medicine G2304 - C2301 |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 6, 2020 | Sep 16, 2024 |
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|
| Atlanta |
| Georgia |
| 30322 |
| United States |
| Northwestern University SC - LCI699C2301 | Chicago | Illinois | 60611 | United States |
| University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | 48109 | United States |
| Columbia University Medical Center New York Presbyterian Neuroendocrine Unit | New York | New York | 10032 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| Cleveland Clinic Foundation | Cleveland | Ohio | 44195 | United States |
| Oregon Health and Science University | Portland | Oregon | 97239 | United States |
| University of Pennsylvania Medical Center Univ Penn | Philadelphia | Pennsylvania | 19104 | United States |
| Medical College of Wisconsin MCW 2 | Milwaukee | Wisconsin | 53226 | United States |
| Sanatorio Guemes | CABA | Buenos Aires | C1180AAX | Argentina |
| Universitaetsklinik fuer Innere Medizin III | Vienna | A-1090 | Austria |
| Gasthuisberg University Hospital | Leuven | 3000 | Belgium |
| Universidade Federal do Ceara | Fortaleza | Ceará | 60020-181 | Brazil |
| Hospital Universitario Clementino Fraga Filho | Rio de Janeiro | Rio de Janeiro | 21941-913 | Brazil |
| Hospital do Servidor Publico Estadual de Sao Paulo | São Paulo | São Paulo | 04039 004 | Brazil |
| Hospital das Clinicas da Faculdade de Medicina da USP | São Paulo | São Paulo | 05403 000 | Brazil |
| USHATE Akad Ivan Penchev | Sofia | 1431 | Bulgaria |
| University of Alberta Hospital | Edmonton | Alberta | T6G 2B7 | Canada |
| QEII Health Sciences Centre | Halifax | Nova Scotia | B3H 1V7 | Canada |
| Centre de recherche du CHUM CRCHUM | Montreal | Quebec | H2W 1T8 | Canada |
| CHUS Hopital Fleurimont | Sherbrooke | Quebec | J1H 5N4 | Canada |
| The First Affiliated Hopsital, Sun Yat-Sun University | Guangzhou | Guangdong | 510080 | China |
| West China Hospital of Sichuan University | Chengdu | Sichuan | 610041 | China |
| Peking University First Hospital | Beijing | 100034 | China |
| Peking Union Medical College Hospital | Beijing | 100730 | China |
| Clinica Los Yoses | San Pedro | San Jose, Costa Rica | 1406 1200 | Costa Rica |
| CHU de Bordeaux | Pessac | Cedex | 33604 | France |
| Hopital Kremlin Bicetre | Le Kremlin-Bicêtre | 94275 | France |
| CHRU de Lille | Lille | 59037 | France |
| Hopital Cochin | Paris | 75014 | France |
| Universitaetsklinikum Erlangen Nuernberg | Erlangen | 91054 | Germany |
| Universitaetsklinikum Muenchen LMU | München | 81377 | Germany |
| All India Institute of Medical Sciences | New Delhi | 110029 | India |
| AOU Osp Riuniti Umberto I GM Lancisi G Salesi Univ Studi | Ancona | AN | 60126 | Italy |
| Azienda Ospedaliera di Padova Università degli Studi | Padova | PD | 35128 | Italy |
| Az Ospedaliero Universitaria Pisana Pres Osped di Cisanello | Pisa | PI | 56124 | Italy |
| A O Universitaria Policlinico Federico II Univ Studi Fed II | Naples | 80131 | Italy |
| National Hospital Organization Nagoya Medical Center | Nagoya | Aichi-ken | 460-0001 | Japan |
| Hyogo College of Medicine Hospital | Nishinomiya | Hyōgo | 663 8501 | Japan |
| Erasmus MC | Rotterdam | 3015 GD | Netherlands |
| SP ZOZ Szpital Uniwersytecki w Krakowie | Krakow | 31-501 | Poland |
| Mazowiecki Szpital Brodnowski | Warsaw | 03 242 | Poland |
| Center for Endocrinology Russian Academy of Med Sciences | Moscow | 117036 | Russia |
| Seoul National University Hospital | Seoul | 03080 | South Korea |
| Yonsei Univ Health System YUCM | Seoul | 03722 | South Korea |
| Hospital Universitario Virgen del Rocio | Seville | Andalusia | 41013 | Spain |
| Complejo Uni. Hosp. A Coruña ( antes Hospital Juan Canalejo) | A Coruña | Galicia | 15006 | Spain |
| Hospital Gregorio Maranon | Madrid | 28009 | Spain |
| Hospital Universitario i Politecnico La Fe | Valencia | 46026 | Spain |
| King Chulalongkorn Memorial Hospital | Bangkok | 10330 | Thailand |
| Siriraj Hospital | Bangkok | 10700 | Thailand |
| Songklanagarind Hospital Endocrinology and Metabolism | Songkhla | 90110 | Thailand |
| Istanbul University Cerrahpasa Faculty of Medicine | Istanbul | TUR | 34098 | Turkey (Türkiye) |
| Marmara University Medical Faculty | Altunizade | 34662 | Turkey (Türkiye) |
| Kocaeli University Medical Faculty | Kocaeli | 41380 | Turkey (Türkiye) |
| COMPLETED |
|
| NOT COMPLETED |
|
|
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.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||||||||||||||
| Age, Customized | Count of Participants | Participants |
| |||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| |||||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| |||||||||||||||||||||||
| Weight | Mean | Standard Deviation | kg |
| ||||||||||||||||||||||
| Height | Mean | Standard Deviation | cm |
| ||||||||||||||||||||||
| Body Mass Index | Mean | Standard Deviation | Kg/m^2 |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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)) | 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. | Posted | Count of Participants | Participants | up to 5 years |
|
|
| ||||||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Count of Participants | Participants | up to of 5 years |
|
|
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
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 2 | 127 | 35 | 127 | 115 | 127 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COVID-19 | Infections and infestations | MedDRA (26.0) | Non-systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Pitituary tumour | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (26.0) | Non-systematic Assessment |
| |
| Adrenal insufficiency | Endocrine disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| ACTH-producing pituitary tumour | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (26.0) | Non-systematic Assessment |
| |
| Acute stress disorder | Psychiatric disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Adenocarcinoma pancreas | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (26.0) | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (26.0) | Non-systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA (26.0) | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (26.0) | Non-systematic Assessment |
| |
| Bile duct stone | Hepatobiliary disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Biliary dilatation | Hepatobiliary disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Device dislocation | Product Issues | MedDRA (26.0) | Non-systematic Assessment |
| |
| Disease progression | General disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Diverticulitis | Gastrointestinal disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Food poisoning | Gastrointestinal disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Gamma-glutamyl transferase increased | Investigations | MedDRA (26.0) | Non-systematic Assessment |
| |
| Hand fracture | Injury, poisoning and procedural complications | MedDRA (26.0) | Non-systematic Assessment |
| |
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA (26.0) | Non-systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Liver function test abnormal | Investigations | MedDRA (26.0) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Paralysis | Nervous system disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Pituitary tumour benign | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (26.0) | Non-systematic Assessment |
| |
| Pituitary-dependent Cushing's syndrome | Endocrine disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (26.0) | Non-systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA (26.0) | Non-systematic Assessment |
| |
| Radius fracture | Injury, poisoning and procedural complications | MedDRA (26.0) | Non-systematic Assessment |
| |
| Renal colic | Renal and urinary disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Renal neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (26.0) | Non-systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Retinal vein thrombosis | Eye disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Ureterolithiasis | Renal and urinary disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Wrist fracture | Injury, poisoning and procedural complications | MedDRA (26.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypertension | Vascular disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA (26.0) | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Adrenal insufficiency | Endocrine disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (26.0) | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (26.0) | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (26.0) | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (26.0) | Non-systematic Assessment |
| |
| Cortisol free urine increased | Investigations | MedDRA (26.0) | Non-systematic Assessment |
| |
| SARs-Cov-2 test positive | Investigations | MedDRA (26.0) | Non-systematic Assessment |
| |
| Blood corticotrophin increased | General disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mario Maldonado | Recordati AG | +41798030344 | maldonado.m@recordati.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 5, 2023 | Sep 16, 2024 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Mar 7, 2022 | Sep 16, 2024 | ICF_002.pdf |
Not provided
| ID | Term |
|---|---|
| D003480 | Cushing Syndrome |
| ID | Term |
|---|---|
| D000308 | Adrenocortical Hyperfunction |
| D000307 | Adrenal Gland Diseases |
| D004700 | Endocrine System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C553306 | Osilodrostat |
Not provided
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| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Title | Measurements |
|---|---|
|
| Treatment-related AEs of CTCAE Grade ≥ 3 |
|
| Serious adverse events |
|
| Treatment-related SAEs |
|
| Fatal SAEs |
|
| Treatment-related fatal SAEs |
|
| Adverse events leading to discontinuation |
|
| Treatment-related AEs leading to discontinuation |
|
| Adverse events leading to dose interruption or adjustment |
|
| Treatment-related AEs leading to dose interruption or adjustment |
|
| Adverse events requiring additional therapy |
|
| Treatment-related AEs requiring additional therapy |
|
| Adverse events of special interest (AESIs) |
|
| Treatment-related AESIs |
|
|