Safety and Efficacy of LCI699 for the Treatment of Patients With Cushing's Disease

• ClinicalTrials.gov Identifier: NCT02180217
• Recruitment Status: Completed
• First Posted: July 2, 2014
• Results First Posted: June 16, 2020
• Last Update Posted: January 6, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

The study aimed to confirm long-term efficacy and safety of LCI699 for the treatment of patients with Cushing's disease. It was a pivotal trial which supported the registration of LCI699 for the treatment of patients with Cushing's disease in the US and the EU.

This is a phase lll, multi-center, double-blind, randomized withdrawal study of LCI699 following a 24 week, single-arm, open-label dose titration and treatment period which evaluated the safety and efficacy of LCI699 for the treatment of patients with Cushing's disease.

Condition or disease	Intervention/treatment	Phase
Cushings Disease	Drug: osilodrostat; Drug: LCI699 matching placebo	Phase 3

Detailed Description:

The primary objective compared the complete response rate at the end of the 8-week period of randomized withdrawal (Week 34) between patients randomized to continued osilodrostat therapy vs.

placebo. The key secondary objective assessed the complete response rate at the end of individual dose titration and treatment with osilodrostat in the initial single-arm, open label period (Week 24).

Eligible patients were randomized in a double-blinded fashion at Week 26 at a 1:1 ratio either to continue treatment with osilodrostat at the same dose or to matching placebo. Randomization was stratified by osilodrostat dose at Week 24 (≤ 5mg bid vs. >5mg bid); and history of pituitary irradiation (yes/no).

The study had four periods combined in the Core Period (Study Period 1 to 4) and an optional Extension Period. The optional Extension Period starting at Week 48.

Study Period 1 consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients (Week 1 to Week 12). Dose adjustments were based on the mean of three 24-hour UFC (mUFC) values as measured by the central laboratory.

During study Period 2 (Week 13 to Week 24), osilodrostat efficacy and safety were assessed at the therapeutic dose determined during study Period 1. Patients whose mUFC became elevated during this period had their osilodrostat dose increased further, if it was tolerated, up to 30 mg bid. Such patients were followed for long-term safety and efficacy and were not considered responders for the key secondary endpoint, hence were not randomized in Study Period 3.

Study Period 3 was a double-blind, placebo-controlled randomized withdrawal (RW) Period (Week 26 to Week 34). In order to be eligible for randomization in study Period 3, patients had to have completed dose titration during study Period 1, and had to be classified as complete responders at Week 24 of study Period 2. Patients not eligible for randomization received open-label osilodrostat until the end of the Core Period (Week 48), unless there was a reason to discontinue from the study prematurely.

During study Period 3, mUFC was measured at scheduled visits every 2 weeks. However, patients were also allowed to have unscheduled visits at any time during the RW if they reported symptoms of hypercortisolism or hypocortisolism.

The dose of study drug remained unchanged for patients who maintained a normal mUFC and did not develop adverse events (AEs) related to study drug during RW. The Investigator could reduce or temporally withhold a dose of study drug for safety reasons at any time during the study, including the RW Period.

During this study period, a patient was discontinued from the RW Period and declared a nonresponder, if the mUFC increased to >1.5×ULN. After discontinuation from RW treatment, or at the end of the RW Period (Week 34), whichever came first, the patient resumed open-label osilodrostat at a dose selected by the Investigator.

Patients who discontinued from the study during the RW Period were no longer in the study, and consequently were not permitted to receive open-label osilodrostat and could not move to study Period 4.

Patients who discontinued from RW treatment due to lack of efficacy resumed open-label osilodrostat at the time of discontinuation, which could occur before Week 34. Patients who were not discontinued during RW resumed open-label osilodrostat at the end of RW (Week 34) and continued osilodrostat thereafter (study Period 4).

The Novartis study team, the patient, the Investigator, and all other site staff remained blinded to treatment assignment from the time of randomization to the time of database lock at the end of the Core Period. Novartis Drug Supply Management department members were unblinded in order to prepare the study drug supplies.

Study Period 4 was a single-arm, open-label therapy (end of Week 34 to Week 48). At the end of Week 34, all patients received open-label osilodrostat treatment. The Investigator had the discretion to select the dose during this period.

Patients continued open-label therapy until Week 48. At Week 48, patients had the option to enter an Extension Period, or discontinue osilodrostat at Week 48 to conclude with an end of Core Period visit 4 weeks off study drug (at Week 52).

Patients who continued to receive clinical benefit, as assessed by the study Investigator, and who wished to enter the Extension Period were re-consented at Week 48. Patients entered the Extension period without interruption of study drug or assessments. At the end of the study, patients who continued to benefit from treatment were offered to participate in a separate long-term safety follow-up study. The optional Extension Period ended after all patients completed Week 72 or discontinued early.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 137 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: It is a double-blind, randomized withdrawal study of LCI699 following a 24 week, single-arm, open-label dose titration and treatment period.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase III, Multi-center, Double-blind, Randomized Withdrawal Study of LCI699 Following a 24 Week, Single-arm, Open-label Dose Titration and Treatment Period to Evaluate the Safety and Efficacy of LCI699 for the Treatment of Patients With Cushing's Disease
• Actual Study Start Date: October 6, 2014
• Actual Primary Completion Date: February 21, 2018
• Actual Study Completion Date: December 4, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: osilodrostat (LCI699); Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then osilodrostat during a double-blind, placebo controlled RW Period.	Drug: osilodrostat; Osilodrostat comes in the form of film-coated tablets for oral administration, in the following strengths: 1 mg, 5 mg, 10 mg, and 20 mg. The maximum dose of osilodrostat was 30 mg bid.; Other Name: LCI699
Placebo Comparator: LCI699 Placebo; Consisted of a single-arm, open-label, osilodrostat dose-titration in individual patients and then placebo during a double-blind, placebo controlled RW Period.	Drug: LCI699 matching placebo; Osilodrostat placebo comes in the form of film-coated tablets for oral administration, in the following strengths: 1 mg, 5 mg, 10 mg, and 20 mg. The maximum dose of osilodrostat placebo was 30 mg bid.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Primary Efficacy Responder at Week 34 by Randomized Treatment and Strata [ Time Frame: Week 34 (8 weeks) ]
   To compare the complete response rate at the end of the 8-week period of randomized withdrawal between randomized patients.A primary efficacy responder is defined as a randomized patient who has mUFC ≤ ULN at Week 34 and who was neither discontinued (study or RW treatment) nor had osilodrostat dose increase above the level at Week 26 during the RW Period of the study. mUFC: mean urinary free cortisol; ULN: Upper Limit of Normal

Secondary Outcome Measures :

1. Percentage of Secondary Efficacy Responder at Week 24 (Key Secondary Endpoint) [ Time Frame: Week 24 ]
   To assess the complete response rate at the end of individual dose-titration and treatment with LCI699 in the initial single-arm, open label period. A Key secondary efficacy responder is defined as a patient in FAS who has mUFC ≤ ULN at Week 24 and the dose of osilodrostat during Study Period 2 (Weeks 13-24) was not increased above the level established at the end of Study Period 1 (Week 12). Patients who had missing mUFC assessment at Week 24 will be counted as non-responders for the key secondary endpoint.
2. Time-to-loss of Control of Mean Urinary Free Cortisol (mUFC) by Randomized Treatment Group [ Time Frame: 8 weeks after randomization ]
   Time-to-loss of control of mUFC during the RW Period, defined as the time (in days) from randomization to the first evidence of loss of control (defined as mUFC assessment >1.5 ULN based on central laboratory result & at least 2 of the associated individual urine samples showing UFC >1.5×ULN) within the RW period. A patient without evidence of loss of control was censored at the date of the last assessment with mUFC ≤ 1.5 ULN. If a patient discontinued randomized treatment without having a UFC assessment, they were censored at the date of randomization. The measure type (number) refers to an Event probability estimate 8 weeks after randomization.
3. Complete Response Rate (CRR) [ Time Frame: Week 12, Week 24, Week 48, Week 72, last observed value ]
   Complete response rate is defined as percentage of enrolled participants with mUFC ≤ ULN
4. Actual Change From Baseline in mUFC [ Time Frame: Weeks 12, 24, 48, 72, last available assessment ]
   Actual change in mUFC from baseline.
5. Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Fasting Glucose [ Time Frame: Baseline, Weeks 48, 72, last available assessment ]
   Actual change in fasting glucose from baseline.
6. Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Hemoglobin A1C (HbA1C) [ Time Frame: Baseline, Weeks 48, 72, last available assessment ]
   Actual change in glycosylated hemoglobin (HbA1c) from baseline.
7. Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Cholesterol, LDL Cholesterol, HDL Cholesterol & Triglyceride [ Time Frame: Baseline, Weeks 48, 72, last available assessment ]
   Actual change in Cholesterol, LDL Cholesterol, HDL Cholesterol & Triglyceride from baseline.
8. Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Sitting Systolic Blood Pressure (SBP) & Sitting Diastolic Blood Pressure (DBP) [ Time Frame: Baseline, Weeks 48, 72, last available assessment ]
   Actual change in sitting SBP & DBP from baseline.
9. Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Weight [ Time Frame: Baseline, Weeks 48, 72, last available assessment ]
   Actual change in weight from baseline.
10. Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Body Mass Index (BMI) [ Time Frame: Baseline, Weeks 48, 72, last available assessment ]
    Actual change in BMI from baseline.
11. Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Waist Circumference [ Time Frame: Baseline, Weeks 48, 72, last available assessment ]
    Actual change in waist circumference from baseline.
12. Actual Change From Baseline in Patient-Reported Outcomes (Cushing's Health-Related Quality of Life (QoL)) - Total Score [ Time Frame: Baseline, Week (W) 48, W72, Last available assessment ]
    Cushing's Disease Health-Related Quality of Life Questionnaire was developed to evaluate quality of life in patients with Cushing's syndrome. It is comprised of 12 items that capture patient responses on 7 concepts: daily activities, healing & pain, mood & self-confidence, social concerns, physical appearance, memory & concern about the future. These items are measured on a 5- point Likert-type scale assessing how often or how much each item has been related to the patient's Cushing's disease in the previous 4 weeks. The raw score is calculated by summing the individual item scores prior to being standardized so that the total score ranges from 0 to 100. Content reliability, sensitivity to change & psychometric properties have been validated in patients with Cushing's disease. Patients were asked to complete the questionnaire prior to clinical assessments being undertaken. Increases from baseline are indicative of an improvement.
13. Actual Change From Baseline in Patient-Reported Outcomes: Beck Depression Inventory-II (BDI-II) [ Time Frame: Baseline, W48, W72, Last available assessment ]
    BDI-II is a patient-reported instrument developed to measure the severity of depression in adults & adolescents aged 13 years & older. It is designed to be completed by the patient on paper & takes approximately 5 minutes to complete. The BDI-II consists of 21 items designed to assess the intensity of depression in clinical & normal patients in the preceding 2 weeks. Items are rated on a 4-point severity scale of 0 ('not at all') to 3 ('extreme' form of each symptom) with differing response options for each item. A global score ranging from 0 to 63 is calculated with a higher score representing a greater level of depression. The following scoring guidelines for interpretation of BDI-II have been suggested (Smarr, 2011): Minimal range =0-13, Mild depression =14-19, Moderate depression =20-28 and Severe depression = 29-63. Patients were asked to complete the questionnaire prior to clinical assessments being undertaken. A reduction from baseline in BDI-II is indicative of an improvement.
14. Actual Change in Patient-Reported Outcomes: EQ-5D-5L Utility Index [ Time Frame: Baseline, W48, W72, Last available assessment ]
    The EQ-5D-5L questionnaire is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. It is cognitively undemanding, taking only a few minutes to complete. Instructions to respondents are included in the questionnaire. The EQ-5D-5L measures 5 items on mobility, self-care, usual activities, pain/discomfort, anxiety/depression, measured on 5 levels: no problems, slight problems, moderate problems, severe problems, & extreme problems. A utility index can be computed from the EQ 5D-5L descriptive system with utility scores ranging from -0.281 (worst imaginable health state) to 1 (best imaginable health state), with -0.281 representing an "unconscious" health state. A single index value is analyzed for the EQ-5D-5L score. An increase from baseline in the EQ-ED-5L utility index is indicative of an improvement.
15. Actual Change in Patient-Reported Outcomes: EQ-5D-5L Vascular Analog Scale (VAS) [ Time Frame: Baseline, W48, W72, Last available assessment ]
    The EQ-5D-5L also includes a 20 cm vertical, VAS (visual analogue scale) with on a scale of 0-100, with endpoints labeled 100 = 'the best health you can imagine' and 0 = 'the worst health you can imagine'. A single index value is analyzed for the VAS score. An increase from baseline in the EQ-ED-5L VAS is indicative of an improvement.
16. Change From Baseline in the Physical Features of Cushing's Disease by Photography [ Time Frame: Week 48, Week 72, Last available assessment ]
    Improvement from baseline to Weeks 48, 72 and End of Treatment (Extension period) in each of the following clinical signs of Cushing's disease by photography: facial rubor, hirsutism, striae, supraclavicular fat pad, dorsal fat pad, proximal muscle wasting (atrophy), central (abdominal) obesity, and ecchymoses (bruises).
17. Change From Baseline in Bone Mineral Density - All Participants [ Time Frame: Baseline, Week 48, Last observed value (LOV) ]
    Actual change from baseline to Week 48 and the LOV in bone mineral density as measured by DXA scan at the lumbar spine and total hip. An increase in bone mineral density is indicative of an improvement..
18. Time-to-escape [ Time Frame: From the first mUFC ≤ ULN to the first mUFC results > 1.5 x ULN with at least 2 individual UFC results > 1.5 x ULN ]
    Escape was defined as the time (in days) from the first mUFC ≤ ULN to the first mUFC results > 1.5 x ULN with at least 2 individual UFC results > 1.5 x ULN the loss happened beyond 12-week dose titration period. Participants randomized to placebo were not included in the analysis.
19. LCI699 Exposures [ Time Frame: from week 2 to 10 at Predose, 0.75h, 1.5h, and 4h post-dose ]
    To evaluate exposures of LCI699 in patients with Cushing's disease. Plasma concentrations (predose, 0.75 h, 1.5 h, and 4 h post-dose) of LCI699. These are the maximum number of PAS subjects analyzed for each incident dose.
20. Percentage of Participants With Complete Response Rate (CRR) [ Time Frame: Week 12, Week 24, Week 48, Week 72, last available assessment ]
    Complete response rate is defined as percentage of enrolled participants with mUFC ≤ ULN.
21. Percentage of Participants With Partial Response Rate (PRR) [ Time Frame: Week 12, Week 24, Week 48, Week 72, last available assessment ]
    Partial response rate is defined as percentage of enrolled participants with ≥ 50% reduction from baseline in mUFC, but mUFC>ULN)
22. Percentage of Participants With Overall Response Rate (ORR) [ Time Frame: Week 12, Week 24, Week 48, Week 72, last available assessment ]
    Overall response rate is defined as percentage of enrolled participants with mUFC ≤ ULN or at least 50% reduction from baseline.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Written informed consent must be obtained before any assessment is performed.
2. Male or female patients aged 18 - 75 years.
3. Patients must have confirmed Cushing's disease that is persistent or recurrent.
4. Patients with a history of prior pituitary surgery must be at least 30 days post-surgery to be eligible for inclusion in this study.
5. Patients that received glucocorticoid replacement therapy post-operatively must have discontinued such therapy for at least one week, or 5 half-lives, whichever is longer, prior to screening.
6. Patients with de novo Cushing's disease can be included only if they are not considered candidates for surgery.
7. Patients with a history of pituitary irradiation can be included, provided that at least 2 years (stereotactic radiosurgery) or 3 years (conventional radiation) have elapsed from the time of last radiation treatment to the time of enrollment into this study.
8. Patients are permitted to washout current drug therapy to meet these entry criteria if they have a known diagnosis of Cushing's disease.

Exclusion Criteria:

1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half lives at the time of enrollment, whichever is longer; or longer if required by local regulations, and for any other limitation of participation in an investigational trial based on local regulations.
2. History of hypersensitivity to LCI699 or to drugs of similar chemical classes.
3. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
4. Patients with risk factors for QTc prolongation or Torsade de Pointes.
5. Pregnant or nursing (lactating) women.
6. 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 after completion of dosing.
7. Patients with compression of the optic chiasm due to a macroadenoma or patients at high risk of compression of the optic chiasm (tumor within 2 mm of optic chiasm).
8. Patients who have a known inherited syndrome as the cause for hormone over secretion.
9. Patients with Cushing's syndrome due to ectopic ACTH secretion or ACTH-independent (adrenal) Cushing's syndrome.
10. Patients who have undergone major surgery within 1 month prior to screening.
11. Hypertensive patients with uncontrolled blood pressure.
12. Diabetic patients with poorly controlled diabetes.
13. Patients who are not euthyroid as judged by the investigator.
14. Patients who have a history of: congestive heart failure, unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, advanced heart block, acute MI less than one year prior to study entry, or clinically significant impairment in cardiovascular function.
15. Patients with moderate to severe renal impairment.
16. Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis, or patients with defined elevated ALT/ AST/ Bilirubin.
17. Patients who have any current or prior medical condition that can interfere with the conduct of the study or the evaluation of its results in the opinion of the investigator or the sponsor's medical monitor.
18. Patients who have a history of alcohol or drug abuse in the 6 month period prior to study treatment.
19. Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will be unable to complete the entire study.

Contacts and Locations

Locations

United States, Colorado

University of Colorado Hospital SC - LCI699C2301

Aurora, Colorado, United States, 80045

United States, Georgia

Emory University School of Medicine G2304 - C2301

Atlanta, Georgia, United States, 30322

United States, Illinois

Northwestern University SC - LCI699C2301

Chicago, Illinois, United States, 60611

United States, Maryland

The Johns Hopkins University School of Medicine Johns Hopkins University

Baltimore, Maryland, United States, 21205

United States, Massachusetts

Massachusetts General Hospital Neuroendocrine Unit

Boston, Massachusetts, United States, 02114

United States, Michigan

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States, 48109

United States, New York

Mount Sinai School of Medicine SC - LCI699C2301

New York, New York, United States, 10029

Columbia University Medical Center New York Presbyterian SC - LCI699C2301

New York, New York, United States, 10032

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

United States, Oregon

Oregon Health and Science University SC LCI699C2301

Portland, Oregon, United States, 97239

United States, Pennsylvania

University of Pennsylvania Clinical Studies Unit Unniv SC

Philadelphia, Pennsylvania, United States, 19104

United States, Wisconsin

Medical College of Wisconsin MCW 2

Milwaukee, Wisconsin, United States, 53226

Argentina

Novartis Investigative Site

Caba, Buenos Aires, Argentina, C1180AAX

Novartis Investigative Site

Caba, Buenos Aires, Argentina, C1426AAI

Austria

Novartis Investigative Site

Wien, Austria, 1090

Bulgaria

Novartis Investigative Site

Sofia, Bulgaria, 1431

Canada, Alberta

Novartis Investigative Site

Edmonton, Alberta, Canada, T6G 2B7

Canada, Nova Scotia

Novartis Investigative Site

Halifax, Nova Scotia, Canada, B3H 1V7

Canada, Quebec

Novartis Investigative Site

Montreal, Quebec, Canada, H2W 1T8

Novartis Investigative Site

Sherbrooke, Quebec, Canada, J1H 5N4

China, Beijing

Novartis Investigative Site

Beijing, Beijing, China, 100730

China, Sichuan

Novartis Investigative Site

Chengdu, Sichuan, China, 610041

China

Novartis Investigative Site

Beijing, China, 100034

Colombia

Novartis Investigative Site

Cali, Colombia

France

Novartis Investigative Site

Le Kremlin Bicetre, France, 94275

Novartis Investigative Site

Lille Cedex, France, 59037

Novartis Investigative Site

Marseille, France, 13385

Novartis Investigative Site

Paris, France, 75014

Novartis Investigative Site

Pessac Cedex, France, 33604

Germany

Novartis Investigative Site

Erlangen, Germany, 91054

Novartis Investigative Site

Muenchen, Germany, 81377

India

Novartis Investigative Site

Bangalore, Karnataka, India, 560054

Novartis Investigative Site

Chandigarh, Punjab, India, 160012

Novartis Investigative Site

Vellore, Tamil Nadu, India, 632004

Novartis Investigative Site

New Delhi, India, 110029

Italy

Novartis Investigative Site

Ancona, AN, Italy, 60126

Novartis Investigative Site

Genova, GE, Italy, 16132

Novartis Investigative Site

Messina, ME, Italy, 98125

Novartis Investigative Site

Milano, MI, Italy, 20122

Novartis Investigative Site

Padova, PD, Italy, 35128

Novartis Investigative Site

Pisa, PI, Italy, 56124

Novartis Investigative Site

Napoli, Italy, 80131

Japan

Novartis Investigative Site

Nagoya, Aichi, Japan, 460-0001

Novartis Investigative Site

Fukuoka city, Fukuoka, Japan, 812-8582

Novartis Investigative Site

Kobe-shi, Hyogo, Japan, 650-0017

Novartis Investigative Site

Nishinomiya, Hyogo, Japan, 663 8501

Novartis Investigative Site

Yokohama, Kanagawa, Japan, 245-8575

Novartis Investigative Site

Bunkyo-ku, Tokyo, Japan, 113-8603

Novartis Investigative Site

Shinjuku-ku, Tokyo, Japan, 160-0023

Korea, Republic of

Novartis Investigative Site

Seoul, Korea, Republic of, 03080

Novartis Investigative Site

Seoul, Korea, Republic of, 03722

Novartis Investigative Site

Seoul, Korea, Republic of, 06351

Netherlands

Novartis Investigative Site

Rotterdam, Netherlands, 3015 GD

Russian Federation

Novartis Investigative Site

Moscow, Russian Federation, 117036

Spain

Novartis Investigative Site

Sevilla, Andalucia, Spain, 41013

Novartis Investigative Site

Madrid, Spain, 28009

Novartis Investigative Site

Madrid, Spain, 28046

Thailand

Novartis Investigative Site

Songkla, Thailand, 90110

Turkey

Novartis Investigative Site

Istanbul, TUR, Turkey, 34098

United Kingdom

Novartis Investigative Site

Sheffield, South Yorkshire, United Kingdom, S10 2JF

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):

Statistical Analysis Plan  [PDF] December 2, 2019

Study Protocol  [PDF] June 29, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Fontaine-Sylvestre C, Letourneau-Guillon L, Moumdjian RA, Berthelet F, Lacroix A. Corticotroph tumor progression during long-term therapy with osilodrostat in a patient with persistent Cushing's disease. Pituitary. 2021 Apr;24(2):207-215. doi: 10.1007/s11102-020-01097-1. Epub 2020 Oct 19.

Pivonello R, Fleseriu M, Newell-Price J, Bertagna X, Findling J, Shimatsu A, Gu F, Auchus R, Leelawattana R, Lee EJ, Kim JH, Lacroix A, Laplanche A, O'Connell P, Tauchmanova L, Pedroncelli AM, Biller BMK; LINC 3 investigators. Efficacy and safety of osilodrostat in patients with Cushing's disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase. Lancet Diabetes Endocrinol. 2020 Sep;8(9):748-761. doi: 10.1016/S2213-8587(20)30240-0. Epub 2020 Jul 27. Erratum In: Lancet Diabetes Endocrinol. 2020 Aug 5;:

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02180217
• Other Study ID Numbers: CLCI699C2301; 2013-004766-34 ( EudraCT Number )
• First Posted: July 2, 2014
• Results First Posted: June 16, 2020
• Last Update Posted: January 6, 2021
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• URL: https://www.clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

LCI699; osilodrostat; Cushings Disease; open-label dose titration; randomized withdrawal

Additional relevant MeSH terms:

ACTH-Secreting Pituitary Adenoma; Pituitary ACTH Hypersecretion; Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pituitary Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site