Cushing's disease
Conditions
Interventions
Product Name: NA
Product Code: LCI699
Pharmaceutical Form: Tablet
INN or Proposed INN: NA
CAS Number: 1315449-72-9
Current Sponsor code: LCI699
Other descriptive name: LCI699
Concentration unit: mg mi
Sponsors
NOVARTIS FARMA S.p.A.
Eligibility
Sex/Gender
All
Inclusion 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 as evidenced by: a. mUFC > 1.5 x ULN (Mean of three 24-hour urine samples collected within 14 days) b. Morning plasma ACTH above lower limit of normal c. Confirmation of pituitary source of excess ACTH is defined by any of the following three criteria: 1. MRI confirmation of pituitary adenoma > 6 mm; OR 2. bilateral inferior petrosal sinus sampling (BIPSS) with either CRH or DDAVP stimulation for patients with a tumor = 6mm. The criteria for a confirmatory BIPSS test are any of the following: • Pre-dose central to peripheral ACTH gradient > 2; • Post-dose central to peripheral ACTH gradient > 3 after either CRH or DDAVP stimulation; OR 3. histopathologic confirmation of an ACTH-staining adenoma in patients who have had prior pituitary surgery. 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 119 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 13
Exclusion criteria
Exclusion criteria: 1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 halflives 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 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. 3. Patients with risk factors for QTc prolongation or Torsade de Pointes, including: patients with a baseline QTcF > 470ms, personal or family history of long QT syndrome, or concomitant medications known to prolong the QT interval, hypokalemia, hypocalcaemia, or hypomagnesemia. 4. Pregnant or nursing (lactating) women. Additional exclusion criteria as per full protocol may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the complete response rate at the end of the 8-week period of randomized withdrawal (Week 34) between patients randomized to continued LCI699 therapy vs. placebo.;Secondary Objective: 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 (Week 24). 1. Compare the time-to-last control of mUFC during the randomized withdrawal period between patients randomized to continued LCI699 therapy and placebo. 2. Assess the complete, partial, and overall response rate at Week 12, Week 24 and Week 48. 3. Assess the change in mUFC during the core and extension periods of the study. 4. To assess the change in cardiovascular-related parameters associated with Cushing’s disease during the core period of the study. 5. Change in Patient-Reported Outcomes (Health- Related Quality of Life) during the core period of the study 6. Change from baseline in the physical features of Cushing’s disease by photography at Week 12, 24, 34, and 48. 7. Percent change from baseline in bone mineral density by DEXA scan at the lumbar spine and total hip at Week 48. Other objectives may apply. ;Primary end point(s): Proportion of randomized patients in each arm with: mUFC = ULN at the end of 8 weeks of randomized withdrawal (Week 34), and were neither discontinued, nor had LCI699 dose increase above the level at week 26 during the randomized withdrawal period.;Timepoint(s) of evaluation of this end point: Week 34 (8 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): key secondary: Proportion of enrolled patients with mUFC = ULN at Week 24 and had no dose increase above the level established at Week 12 between Week 13 and Week 24. Other secondary: 1. Time-to-last control of mUFC, which is defined as the time (in days) from randomization to the last mUFC collection that was = ULN before early discontinuation or completion of randomized withdrawal period, whichever is earlier 2. • Complete response rate: proportion of enrolled patients with mUFC = ULN at Week 12, Week 24 and Week 48. • Partial response rate: proportion of enrolled patients with > 50% reduction from baseline in mUFC, but mUFC > ULN) at Week 12, Week 24, and Week 48. • Overall response rate: proportion of enrolled patients with mUFC = ULN or at least 50% reduction from baseline at Week 12, Week 24, and Week 48. 3. • Actual and percentage change in mUFC from baseline to each postbaseline visit during the core and extension at which UFC is collected • Actual and percentage change in mUFC from the time of randomization (Week 26) to the end of the randomized withdrawal period (Week 34), or the last mUFC measurement prior to early discontinuation, whichever occurs earlier. 4. • Actual and percentage change from baseline to Week 12, Week 24 and Week 48 in: fasting glucose, HbA1c, fasting lipid profile, blood pressure, body weight, BMI and waist circumference • Actual and percentage change from the randomization (Week 26) to the end of randomized withdrawal period (Week 34), or the last measurement available prior to early discontinuation, whichever occurs earlier (see bullet above for individual parameters). 5. • Change in standardized score of CushingQoL, Beck Depression Inventory-II, and EQ-5D-5L, from baseline to Week 24 and Week 48. • Change in standardized score of CushingQoL, Beck Depression Inventory-II, and EQ-5D-5L, from the randomization (Week 26) to the end of randomized withdrawal period (Week 34), or the last measur | — |
Countries
Argentina, Australia, Austria, Bulgaria, Canada, China, Colombia, France, Germany, India, Italy, Japan, Korea, Republic of, Netherlands, Russian Federation, Slovakia, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactDrug Regulatory Affairs
NOVARTIS FARMA S.p.A.
Outcome results
None listed