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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02180217




Registration number
NCT02180217
Ethics application status
Date submitted
17/06/2014
Date registered
2/07/2014

Titles & IDs
Public title
Safety and Efficacy of LCI699 for the Treatment of Patients With Cushing's Disease
Scientific 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
Secondary ID [1] 0 0
2013-004766-34
Secondary ID [2] 0 0
CLCI699C2301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cushings Disease 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - osilodrostat
Treatment: Drugs - LCI699 matching placebo

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.

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.


Treatment: Drugs: 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.

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Primary Efficacy Responder at Week 34 by Randomized Treatment and Strata
Timepoint [1] 0 0
Week 34 (8 weeks)
Secondary outcome [1] 0 0
Percentage of Secondary Efficacy Responder at Week 24 (Key Secondary Endpoint)
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
Time-to-loss of Control of Mean Urinary Free Cortisol (mUFC) by Randomized Treatment Group
Timepoint [2] 0 0
8 weeks after randomization
Secondary outcome [3] 0 0
Complete Response Rate (CRR)
Timepoint [3] 0 0
Week 12, Week 24, Week 48, Week 72, last observed value
Secondary outcome [4] 0 0
Actual Change From Baseline in mUFC
Timepoint [4] 0 0
Weeks 12, 24, 48, 72, last available assessment
Secondary outcome [5] 0 0
Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Fasting Glucose
Timepoint [5] 0 0
Baseline, Weeks 48, 72, last available assessment
Secondary outcome [6] 0 0
Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Hemoglobin A1C (HbA1C)
Timepoint [6] 0 0
Baseline, Weeks 48, 72, last available assessment
Secondary outcome [7] 0 0
Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Cholesterol, LDL Cholesterol, HDL Cholesterol & Triglyceride
Timepoint [7] 0 0
Baseline, Weeks 48, 72, last available assessment
Secondary outcome [8] 0 0
Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Sitting Systolic Blood Pressure (SBP) & Sitting Diastolic Blood Pressure (DBP)
Timepoint [8] 0 0
Baseline, Weeks 48, 72, last available assessment
Secondary outcome [9] 0 0
Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Weight
Timepoint [9] 0 0
Baseline, Weeks 48, 72, last available assessment
Secondary outcome [10] 0 0
Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Body Mass Index (BMI)
Timepoint [10] 0 0
Baseline, Weeks 48, 72, last available assessment
Secondary outcome [11] 0 0
Actual Change From Baseline in Cardiovascular-related Parameter Associated With Cushing's Disease: Waist Circumference
Timepoint [11] 0 0
Baseline, Weeks 48, 72, last available assessment
Secondary outcome [12] 0 0
Actual Change From Baseline in Patient-Reported Outcomes (Cushing's Health-Related Quality of Life (QoL)) - Total Score
Timepoint [12] 0 0
Baseline, Week (W) 48, W72, Last available assessment
Secondary outcome [13] 0 0
Actual Change From Baseline in Patient-Reported Outcomes: Beck Depression Inventory-II (BDI-II)
Timepoint [13] 0 0
Baseline, W48, W72, Last available assessment
Secondary outcome [14] 0 0
Actual Change in Patient-Reported Outcomes: EQ-5D-5L Utility Index
Timepoint [14] 0 0
Baseline, W48, W72, Last available assessment
Secondary outcome [15] 0 0
Actual Change in Patient-Reported Outcomes: EQ-5D-5L Vascular Analog Scale (VAS)
Timepoint [15] 0 0
Baseline, W48, W72, Last available assessment
Secondary outcome [16] 0 0
Change From Baseline in the Physical Features of Cushing's Disease by Photography
Timepoint [16] 0 0
Week 48, Week 72, Last available assessment
Secondary outcome [17] 0 0
Change From Baseline in Bone Mineral Density - All Participants
Timepoint [17] 0 0
Baseline, Week 48, Last observed value (LOV)
Secondary outcome [18] 0 0
Time-to-escape
Timepoint [18] 0 0
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
Secondary outcome [19] 0 0
LCI699 Exposures
Timepoint [19] 0 0
from week 2 to 10 at Predose, 0.75h, 1.5h, and 4h post-dose
Secondary outcome [20] 0 0
Percentage of Participants With Complete Response Rate (CRR)
Timepoint [20] 0 0
Week 12, Week 24, Week 48, Week 72, last available assessment
Secondary outcome [21] 0 0
Percentage of Participants With Partial Response Rate (PRR)
Timepoint [21] 0 0
Week 12, Week 24, Week 48, Week 72, last available assessment
Secondary outcome [22] 0 0
Percentage of Participants With Overall Response Rate (ORR)
Timepoint [22] 0 0
Week 12, Week 24, Week 48, Week 72, last available assessment

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/10/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/12/2019
Sample size
Target
Accrual to date
Final
137
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Oregon
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Wisconsin
Country [11] 0 0
Argentina
State/province [11] 0 0
Buenos Aires
Country [12] 0 0
Austria
State/province [12] 0 0
Wien
Country [13] 0 0
Bulgaria
State/province [13] 0 0
Sofia
Country [14] 0 0
Canada
State/province [14] 0 0
Alberta
Country [15] 0 0
Canada
State/province [15] 0 0
Nova Scotia
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
China
State/province [17] 0 0
Beijing
Country [18] 0 0
China
State/province [18] 0 0
Sichuan
Country [19] 0 0
Colombia
State/province [19] 0 0
Cali
Country [20] 0 0
France
State/province [20] 0 0
Le Kremlin Bicetre
Country [21] 0 0
France
State/province [21] 0 0
Lille Cedex
Country [22] 0 0
France
State/province [22] 0 0
Marseille
Country [23] 0 0
France
State/province [23] 0 0
Paris
Country [24] 0 0
France
State/province [24] 0 0
Pessac Cedex
Country [25] 0 0
Germany
State/province [25] 0 0
Erlangen
Country [26] 0 0
Germany
State/province [26] 0 0
Muenchen
Country [27] 0 0
India
State/province [27] 0 0
Karnataka
Country [28] 0 0
India
State/province [28] 0 0
Punjab
Country [29] 0 0
India
State/province [29] 0 0
Tamil Nadu
Country [30] 0 0
India
State/province [30] 0 0
New Delhi
Country [31] 0 0
Italy
State/province [31] 0 0
AN
Country [32] 0 0
Italy
State/province [32] 0 0
GE
Country [33] 0 0
Italy
State/province [33] 0 0
ME
Country [34] 0 0
Italy
State/province [34] 0 0
MI
Country [35] 0 0
Italy
State/province [35] 0 0
PD
Country [36] 0 0
Italy
State/province [36] 0 0
PI
Country [37] 0 0
Italy
State/province [37] 0 0
Napoli
Country [38] 0 0
Japan
State/province [38] 0 0
Aichi
Country [39] 0 0
Japan
State/province [39] 0 0
Fukuoka
Country [40] 0 0
Japan
State/province [40] 0 0
Hyogo
Country [41] 0 0
Japan
State/province [41] 0 0
Kanagawa
Country [42] 0 0
Japan
State/province [42] 0 0
Tokyo
Country [43] 0 0
Korea, Republic of
State/province [43] 0 0
Seoul
Country [44] 0 0
Netherlands
State/province [44] 0 0
Rotterdam
Country [45] 0 0
Russian Federation
State/province [45] 0 0
Moscow
Country [46] 0 0
Spain
State/province [46] 0 0
Andalucia
Country [47] 0 0
Spain
State/province [47] 0 0
Madrid
Country [48] 0 0
Thailand
State/province [48] 0 0
Songkla
Country [49] 0 0
Turkey
State/province [49] 0 0
TUR
Country [50] 0 0
United Kingdom
State/province [50] 0 0
South Yorkshire

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.clinicalstudydatarequest.com


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02180217