Placebo-controlled study of the safety and efficacy of osilodrostat in patients with Cushing's Disease

• Register: EUCTR
• Last refreshed on: 19 April 2022
• Main ID: EUCTR2014-004092-23-ES
• Date of registration: 18/03/2016
• Prospective Registration: Yes
• Primary sponsor: Novartis Farmacéutica, S.A.
• Public title: Placebo-controlled study of the safety and efficacy of osilodrostat in patients with Cushing's Disease
• Scientific title: A Phase III, multi-center, randomized, double-blind, 48 week study with an initial 12 week placebo-controlled period to evaluate the safety and efficacy of osilodrostat in patients with Cushing?s disease - LINC-4
• Date of first enrolment: 29/04/2016
• Target sample size: 69
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004092-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Brazil, Denmark, Greece, Poland, Portugal, Russian Federation, Spain, Switzerland, Thailand, Turkey, United States

Contacts

• Name: Departamento Médico (ICRO)
• Affiliation: Novartis Farmacéutica, S.A.

• Name: Departamento Médico (ICRO)
• Affiliation: Novartis Farmacéutica, S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
Male or female patients aged 18 - 75 years
Confirmed CD that is persistent or recurrent
For patients with a history of pituitary irradiation: at least 2 years since stereotactic radiosurgery (SRS), and 3 years since conventional (fractionated) radiation
Able to communicate well with the investigator, to understand and comply with the requirements of the study
Washout of any current drug therapy for CD
Additional inclusion criteria as per full protocol may apply.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 55
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 14

Exclusion criteria:
- Use of other investigational drugs at the time of enrollment
- Pseudo-Cushing?s syndrome
- History of malignancy of any organ system
- Risk factors for QTc prolongation or Torsade de Pointes
- Pregnant or nursing (lactating) women
- Women of child-bearing potential, unless they are using highly effective methods of contraception
Additional exclusion criteria as per full protocol may apply.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Cushing's disease
MedDRA version: 18.1 Level: LLT Classification code 10011651 Term: Cushing's disease System Organ Class: 100000004860

Therapeutic area: Diseases [C] - Hormonal diseases [C19]

Intervention(s)

Product Name: osilodrostat 1mg
Product Code: LCI699
Pharmaceutical Form: Tablet
INN or Proposed INN: osilodrostat
Current Sponsor code: LCI699
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: osilodrostat 5mg
Product Code: LCI699
Pharmaceutical Form: Tablet
INN or Proposed INN: osilodrostat
Current Sponsor code: LCI699
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: osilodrostat 10mg
Product Code: LCI699
Pharmaceutical Form: Tablet
INN or Proposed INN: osilodrostat
Current Sponsor code: LCI699
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: osilodrostat 20mg
Product Code: LCI699
Pharmaceutical Form: Tablet
INN or Proposed INN: osilodrostat
Current Sponsor code: LCI699
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To demonstrate the superiority of osilodrostat compared to placebo in achieving a complete response (mUFC ? ULN) at Week 12

Secondary Objective: To assess the complete response rate after 24 weeks of open-label osilodrostat treatment
To assess the overall response rate at Week 12, 36, and 48
To assess the change in mUFC
To compare the time-to-first control of UFC during period 1 between treatment arms
To assess the time-to-escape
To assess cardiovascular and metabolic-related parameters associated with CD
To assess the change over time in Health Related Quality of Life
To assess the change from baseline in physical features of CD
To assess the change from baseline in bone mineral density
To evaluate pharmacokinetic exposure of osilodrostat
To determine the safety and tolerability of osilodrostat
Other objectives may apply

Primary end point(s): The proportion of randomized patients with a complete response, i.e. mUFC ?

Timepoint(s) of evaluation of this end point: Week 12

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 36

Secondary end point(s): To assess the complete response rate after 24 weeks of open-label osilodrostat treatment

Secondary ID(s)

CLCI699C2302

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date: 28/04/2016
Contact:

Results

• Results available: Yes
• Date Posted: 21/08/2021
• Date Completed: 31/12/2020
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-004092-23/results