Non-interventional Study on Osilodrostat in Patients With Endogenous Cushing's Syndrome (LINC6)

A Non-interventional Study to Assess the Long-term Safety and Efficacy of Osilodrostat in Patients With Endogenous Cushing's Syndrome

This is a non-interventional, multinational, multi-centre study with primary data collection, to further document the safety and efficacy of osilodrostat administered in routine clinical practice in patients treated with osilodrostat for endogenous Cushing's Syndrome

Study Overview

• Status: Active, not recruiting
• Conditions: Endogenous Cushing's Syndrome
• Intervention / Treatment: Drug: Osilodrostat

Detailed Description

This is a non-interventional, multinational, multi-centre study with primary data collection, to further document the safety and efficacy of osilodrostat administered in routine clinical practice in patients treated with osilodrostat for endogenous Cushing's Syndrome. This study is observational in nature and does not impose a therapy protocol, diagnostic/therapeutic interventions or a visit schedule.

Patients with endogenous Cushing's Syndrome who are treated with osilodrostat alone or in combination with other therapies will be considered eligible for study enrolment. Each patient enrolled in the study will be followed up for 3 years from study entry. Patients who discontinue prior to the end of the 3-year period will be followed-up for 3 months after discontinuation of osilodrostat and will be included in the analysis.

The total number of patients enrolled in this study will be approximately 201. Assuming a recruitment period of 3 years, the total study duration from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) will be 6 years. The maximum duration for the individual patient is 3 years.

• Study Type: Observational
• Enrollment (Actual): 206

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33604
    • Hopital Haut-Leveque
  • Bron, France, 69677
    • Hospices Civiles de Lyon
  • Grenoble, France, 38043
    • CHU de Grenoble site Nord
  • Le Kremlin-Bicêtre, France, 94275
    • Groupement Hospitalier Sud - Hôpital Bicêtre
  • Lille, France, 59037
    • Hopital Claude Huriez - CHRU Lille
  • Marseille, France, 13005
    • Hopital de la Conception - APHM
  • Nancy, France, 54500
    • Hôpital de Brabois
  • Nantes, France, 44800
    • CHU de Nantes-Hopital Laennec
  • Paris, France, 75679
    • Hôpital Cochin
  • Toulouse, France, 31000
    • Hôpital Larrey
• Germany
  • Berlin, Germany, 10117
    • Charité Universitaetsmedizin Berlin
  • Berlin, Germany, 10117
    • Medicover Berlin-Mitte MVZ
  • Cologne, Germany, 50939
    • Medicover Köln
  • Düsseldorf, Germany
    • Universitaet Bielefeld - Klinikum Bielefeld - Mitte
  • Frankfurt, Germany, 60596
    • Endokrinologikum Frankfurt
  • Frankfurt, Germany, 60590
    • Universitaetsklinikum Frankfurt Goethe-Universitaet
  • Hamburg, Germany, 20095
    • Amedes Experts
  • Munich, Germany, 81667
    • Medicover Neuroendokrinologie
  • Munich, Germany
    • Ludwig-Maximilians University of Munich
  • Oldenburg, Germany, 26122
    • Medicover MVZ Oldenburg
  • Würzburg, Germany, 97080
    • Universitaetsklinikum Wuerzburg
• Italy
  • Ancona, Italy, 60126
    • Azienda Ospedaliero Universitaria Ospedali Riuniti
  • Milan, Italy, 20122
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Universitaria "Federico II"
  • Roma, Italy, 00189
    • Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza
  • Roma, Italy, 00186
    • Policlinico Umberto I
• Netherlands
  • Nijmegen, Netherlands, 6500
    • Radboud University Nijmegen
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus MC
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Schl-med
  • Kentucky
    • Covington, Kentucky, United States, 41011
      • St Elizabeth Physicians
  • Massachusetts
    • Boston, Massachusetts, United States, 02114-2696
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10017
      • NYU Grossman School of Medicine
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center (MSKCC) - New York
  • Ohio
    • Columbus, Ohio, United States, 43201
      • Endocrinology Research Associates, Inc.
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The patient population will consist of adult male and female patients with endogenous Cushing's Syndrome. Eligible patients for the study must be treated with osilodrostat. Investigators need to ensure that patients enrolled in this study meet the study inclusion and exclusion criteria listed in the protocol.

Description

Inclusion Criteria:

• Written informed consent obtained prior to registration of any patient data
• Male or female patients aged 18 years or older with endogenous CS treated with osilodrostat. Treatment with osilodrostat can either be initiated at the first visit of the study or can have been initiated before screening.

Exclusion Criteria:

• Patients with exogenous CS
• Patients with Pseudo CS
• Patients participating in an interventional clinical trial with an investigational drug.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Osilodrostat; Osilodrostat - tablets of 1mg, 5mg, 10mg - based on patients needs - up to 3 years	Drug: Osilodrostat; oral administration of Osilodrostat tablets at different doses according to patient's need; Other Names: Isturisa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of osilodrostat-related adverse events and serious adverse events	Number of participants with Adverse Events and Serious Adverse Events	3 years of treatment with osilodrostat

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Short and long-term efficacy of osilodrostat	Complete response rate: proportion of enrolled patients with mean Urinary Free Cortisol (mUFC) ≤ ULN	at baseline before treatment start, after 1 month of treatment, then every 3 months in the first year and every 6 months thereafter through study completion up to three years
Short and long-term efficacy of osilodrostat	Partial response rate: proportion of enrolled patients with ≥ 50% reduction from baseline in mean urinary free cortisol (mUFC), (but mUFC > ULN)	at baseline before treatment start, after 1 month of treatment, then every 3 months in the first year and every 6 months thereafter through study completion up to three years
Short and long-term efficacy of osilodrostat	Overall response rate: proportion of enrolled patients with mean urinary free cortisol (mUFC) ≤ ULN or at least 50% reduction from baseline	at baseline before treatment start, after 1 month of treatment, then every 3 months in the first year and every 6 months thereafter through study completion up to three years
Changes in pituitary tumour size	Actual and percentage change from baseline in pituitary tumour size	at baseline before treatment start, after 6 months of treatment, then every 12 months through study completion up to three years
Incidence of Adverse Events (Safety and Tolerability)	Incidence of adverse events and laboratory abnormalities using the National Cancer Institute-Common Toxicology Criteria (NCI-CTC) grading scale (version 5.0).	3 years of treatment with osilodrostat
Change of mean urinary free cortisol (mUFC)	Actual and percentage change from baseline in mean urinary free cortisol (mUFC)	at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years
Change of Serum Cortisol	Actual and percentage change from baseline in Serum Cortisol	at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years
Change of Late Salivary Cortisol	Actual and percentage change from baseline in Late Salivary Cortisol	at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years
Change of adrenocorticotropic hormone (ACTH)	Actual and percentage change from baseline in adrenocorticotropic hormone (ACTH)	at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years
Normalization of Serum Cortisol	Proportion of patients achieving normalisation of Serum Cortisol	at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years
Normalization of Late Salivary Cortisol	Proportion of patients achieving normalisation of Late Salivary Cortisol	at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years
Normalization of adrenocorticotropic hormone (ACTH)	Proportion of patients achieving normalisation of adrenocorticotropic hormone (ACTH)	at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years
Change in Fasting Glucose	Actual and percentage change from baseline in fasting glucose	at baseline before treatment start, then every 3 months through study completion up to three years
Change in HbA1c	Actual and percentage change from baseline in HbA1c	at baseline before treatment start, then every 3 months through study completion up to three years
Change in Fasting Lipid Profile	Actual and percentage change from baseline in Fasting Lipid Profile	at baseline before treatment start, then every 3 months through study completion up to three years
Change in Serum Insulin	Actual and percentage change from baseline in Serum Insulin	at baseline before treatment start, then every 3 months through study completion up to three years
Change in Blood Pressure	Actual and percentage change from baseline in Blood Pressure	at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years
Change in Body Weight	Actual and percentage change from baseline in Body Weight	at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years
Change in Body Mass Index (BMI)	Actual and percentage change from baseline in Body Mass Index (BMI)	at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years
Change in Waist Circumference	Actual and percentage change from baseline in Waist Circumference	at baseline before treatment start, after 1 month of treatment, then every 3 months through study completion up to three years
Change in Facial Rubor	Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Facial Rubor	at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years
Change in Hirsutism	Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Hirsutism	at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years
Change in Striae	Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Striae	at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years
Change in Supraclavicular fat pad	Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Supraclavicular fat pad	at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years
Change in Dorsal fat pad	Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Dorsal fat pad	at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years
Change in Proximal muscle wasting (atrophy)	Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Proximal muscle wasting (atrophy)	at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years
Change in Central (abdominal) obesity	Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Central (abdominal) obesity	at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years
Change in Ecchymoses (bruises)	Change from baseline in incidence and grade of severity at physical examination of the Cushing's syndrome clinical feature Ecchymoses (bruises)	at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years
Changes in Patient-Reported Outcome (PRO) questionnaire Cushing Quality of Life (QoL)	Actual and percentage change from baseline in score of PRO questionnaire CushingQoL. The minimum and maximum values are 12 and 60 respectively, where higher score means a better outcome	at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years
Changes in Patient-Reported Outcome (PRO) questionnaire Euro Quality of Life (EQ) - 5 Dimensions (5D) - 5 Levels (5L)	Actual and percentage change from baseline in score of PRO questionnaire EQ-5D-5L. The minimum and maximum values for the questions are 11111 and 55555 respectively, where higher score is a worst outcome. For the visual analogue scale minimum and maximum values are 0 and 100 respectively, where higher score means a better outcome	at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years
Changes in Patient-Reported Outcome (PRO) questionnaire Beck Depression Inventory II (BDI-II)	Actual and percentage change from baseline in score of PRO questionnaire BDI-II. The minimum and maximum values are 1 and 63 respectively, where higher score means a worse outcome	at baseline before treatment start, after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years
Changes in Patient-Reported Outcome (PRO) questionnaire Patient Global Impression of Change (PGIC)	Actual and percentage change in score of PRO questionnaire PGIC. The minimum and maximum values of the question are 1 and 7 respectively, where higher score means a better outcome. For the visual analogue scale minimum and maximum values are 0 and 10 respectively, where higher score means a worse outcome	after 3 months of treatment, after 6 months of treatment, then every 6 months through study completion up to three years

Collaborators and Investigators

• Sponsor: RECORDATI GROUP
• Investigators: Study Chair: Mario Maldonado, MD, Recordati AG - Head of Clinical Development

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2022
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: May 3, 2022
• First Submitted That Met QC Criteria: May 16, 2022
• First Posted (Actual): May 19, 2022

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Cushing's syndrome; Osilodrostat
• Additional Relevant MeSH Terms: Endocrine System Diseases; Adrenal Gland Diseases; Adrenocortical Hyperfunction; Cushing Syndrome; Osilodrostat
• Other Study ID Numbers: LCI699-RECAG-PASS-0572

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No