Clinical trial NCT03606408: Roll-over Study in Patients With Endogenous Cushing's Syndrome for LCI699
Official title: An Open-label, Multi-center, Roll-over Study to Assess Long Term Safety in Patients With Endogenous Cushing's Syndrome Who Have Completed a Prior Novartis-sponsored Osilodrostat (LCI699) Study and Are Judged by the Investigator to Benefit From Continued Treatment With Osilodrostat
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cushing's Syndrome
Keywords: Cushing's syndrome
osilodrostat
LCI699
endogenous Cushing's syndrome
Lead sponsor: RECORDATI GROUP
Sponsor class: INDUSTRY
First posted: 2018-07-30
Enrollment: 127
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Adverse/Serious Adverse Events
timeFrame: up to 5 years
Secondary outcomes:
measure: Percentage of Patients With Clinical Benefit
timeFrame: up to of 5 years
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Atlanta
country: United States
facility: Emory University School of Medicine G2304 - C2301
state: Georgia
city: Chicago
country: United States
facility: Northwestern University SC - LCI699C2301
state: Illinois
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: New York
country: United States
facility: Columbia University Medical Center New York Presbyterian Neuroendocrine Unit
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Medical Center Univ Penn
state: Pennsylvania
city: Milwaukee
country: United States
facility: Medical College of Wisconsin MCW 2
state: Wisconsin
city: Caba
country: Argentina
facility: Sanatorio Guemes
state: Buenos Aires
city: Vienna
country: Austria
facility: Universitaetsklinik fuer Innere Medizin III
city: Leuven
country: Belgium
facility: Gasthuisberg University Hospital
city: Fortaleza
country: Brazil
facility: Universidade Federal do Ceara
state: CE
city: Rio de Janeiro
country: Brazil
facility: Hospital Universitario Clementino Fraga Filho
state: RJ
city: Sao Paulo
country: Brazil
facility: Hospital do Servidor Publico Estadual de Sao Paulo
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina da USP
state: SP
city: Sofia
country: Bulgaria
facility: USHATE Akad Ivan Penchev
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
city: Montreal
country: Canada
facility: Centre de recherche du CHUM CRCHUM
state: Quebec
city: Sherbrooke
country: Canada
facility: CHUS Hopital Fleurimont
state: Quebec
city: Guangzhou
country: China
facility: The First Affiliated Hopsital, Sun Yat-Sun University
state: Guangdong
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: San Pedro
country: Costa Rica
facility: Clinica Los Yoses
state: San Jose, Costa Rica
city: Pessac
country: France
facility: CHU de Bordeaux
state: Cedex
city: Le Kremlin Bicetre
country: France
facility: Hopital Kremlin Bicetre
city: Lille Cedex
country: France
facility: CHRU de Lille
city: Paris
country: France
facility: Hopital Cochin
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen Nuernberg
city: Muenchen
country: Germany
facility: Universitaetsklinikum Muenchen LMU
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
city: Ancona
country: Italy
facility: AOU Osp Riuniti Umberto I GM Lancisi G Salesi Univ Studi
state: AN
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova Università degli Studi
state: PD
city: Pisa
country: Italy
facility: Az Ospedaliero Universitaria Pisana Pres Osped di Cisanello
state: PI
city: Napoli
country: Italy
facility: A O Universitaria Policlinico Federico II Univ Studi Fed II
city: Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center
state: Aichi
city: Nishinomiya
country: Japan
facility: Hyogo College of Medicine Hospital
state: Hyogo
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei Univ Health System YUCM
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Krakow
country: Poland
facility: SP ZOZ Szpital Uniwersytecki w Krakowie
city: Warszawa
country: Poland
facility: Mazowiecki Szpital Brodnowski
city: Moscow
country: Russian Federation
facility: Center for Endocrinology Russian Academy of Med Sciences
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
state: Andalucia
city: La Coruna
country: Spain
facility: Complejo Uni. Hosp. A Coruña ( antes Hospital Juan Canalejo)
state: Galicia
city: Madrid
country: Spain
facility: Hospital Gregorio Maranon
city: Valencia
country: Spain
facility: Hospital Universitario i Politecnico La Fe
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Songkla
country: Thailand
facility: Songklanagarind Hospital Endocrinology and Metabolism
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Faculty of Medicine
state: TUR
city: Altunizade
country: Turkey
facility: Marmara University Medical Faculty
city: Kocaeli
country: Turkey
facility: Kocaeli University Medical Faculty
Study officials:
affiliation: Recordati AG
name: Recordati
role: STUDY_DIRECTOR
References: