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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT02180217
First received: June 17, 2014
Last updated: March 21, 2017
Last verified: March 2017

June 17, 2014
March 21, 2017
October 6, 2014
March 18, 2019   (Final data collection date for primary outcome measure)
Proportion of randomized patients with: mUFC </= ULN [ Time Frame: Week 34 (8 weeks) ]

To compare the complete response rate at the end of the 8-week period. These patients will not have discountinued during the randomized withdrawal period, between patients randomized to continue LCI699 therapy and placebo.

mUFC: mean Urinary free Cortisol) ULN: Upper Limit of Normal

Same as current
Complete list of historical versions of study NCT02180217 on ClinicalTrials.gov Archive Site
  • Proportion of enrolled patients with mUFC </= ULN [ 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. These patients would have had no dose increase above the level established at Week 12 between Week 13 and Week 24.
  • Time-to-last control of mUFC [ Time Frame: Betwwen week 26 and week 34, up to a maximum of 8 weeks (56 days) ]
    Time-to-last control of mUFC is defined as the time (in days) from randomization to the last mUFC collection that was </= ULN before early discontinuation or completion of randomized withrdrawal period, whichever is earlier.
  • Complete Response Rate (CRR) [ Time Frame: Week 12, Week 24, Week 48 ]
    Complete response rate is defined as proportion of enrolled patients with mUFC</= ULN at Week 12, Week 24 and Week 48.
  • Change in mUFC [ Time Frame: baseline, post-baseline, Week 26, Week 34 ]
    Actual and percentage change in mUFC from baseline to each post-baseline 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.
  • Change in cardiovascular-related parameters associated with Cushing's disease [ Time Frame: Baseline, Week 12, 24, 26, 34 and 48 ]
    This is for the actual and percentage change. The cardiovascular-related parameters include fasting glucose, HbA1c, fasting lipid profile, blood pressure, body weight, BMI and waist circumference.
  • Change in Patient-Reported Outcomes (Health-Related Quality of Life) [ Time Frame: Baseline, Week 24, 26, 34 and 48 ]
    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 measurement prior to early discontinuation, whichever occurs earlier.
  • Change in the physical features of Cushing's disease by photography [ Time Frame: Weeks 12, 24, 34, and 48. ]
    Mean change from baseline to Week 12, 24, 34, and 48 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).
  • Change in bone mineral density [ Time Frame: Baseline, Week 48 ]
    Actual and percent change from baseline to Week 48 in bone mineral density as measured by DEXA scan at the lumbar spine and total hip.
  • Time-to-escape [ Time Frame: At first mUFC results > 1.5 x ULN ]
    Time-to-escape is defined as time (in days) from the first mUFC </= ULN to the first mUFC results > 1.5 x ULN.
  • Number of patients with adverse events (AEs) [ Time Frame: Every visit for 96 weeks ]
    For safety and tolerabuility, adverse events and laboratory abnormalities will be assessed using the National Cancer Institute-Common Toxicology Criteria (NCI-CTC) grading scale (version 4.0). AEs of special interest, as reported by the investigator, or by laboratory evaluation, electrocardiogam (ECG), Holter recording, and pituitary magnetic resonance imaging (MRI).
  • Plasma concentration of LCI699 [ Time Frame: Predose, 0.5 h, 1.5 h, and 3.5 h post-dose ]
    To evaluate exposures of LCI699 in patients with Cushing's disease. Plasma concentrations (predose, 0.5 h, 1.5 h, and 3.5 h post-dose) of LCI699
  • Partial Response Rate (PRR) [ Time Frame: Week 12, Week 24, Week 48 ]
    Partial response rate is defined as 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 (ORR) [ Time Frame: Week 12, Week 24, Week 48 ]
    Overall response rate is defined as proportion of enrolled patients with mUFC </= ULN or at least 50% reduction from baseline at Week 12, Week 24, Week 48.
  • Actual and percentage change in mUFC [ Time Frame: Start of randomization (Week 26) to end of randomization (Week 34) ]
    Actual and percentage change in mUFC from baseline to each post-baseline 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.
Same as current
Not Provided
Not Provided
 
Safety and Efficacy of LCI699 for the Treatment of Patients With Cushing's Disease
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
The study aims to confirm long-term efficacy and safety of LCI699 for the treatment of patients with Cushing's disease. It is a pivotal trial intended to support the registration of LCI699 for the treatment of patients with Cushing's disease in the EU, Japan, and other countries.
Not Provided
Interventional
Phase 3
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Cushing's Disease
Drug: LCI699
Experimental: LCI699
Intervention: Drug: LCI699
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
132
March 18, 2019
March 18, 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Written informed consent must be obtained before any assessment is performed.
  • Male or female patients aged 18-75 years
  • Patients must have confirmed Cushing's disease that is persistent or recurrent as evidenced by:

    1. mUFC> 1.5 x ULN (mean of three 24-hour urine samples collected within 14 days)
    2. morning plasma ACTH above lower limit of normal
    3. 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.
  • Patients with a history of prior pituitary surgery must be at least 30 days post-surgery to be eligible for inclusion in this study.

Exclusion Criteria:

  • Use of other investigational durgs 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.
  • history of hypersensitivity to LCI699 or to drugs of similar chemical classes.
  • hisotry 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 metasteses.
  • patients with risk factors for QTc prolongation or Torsade de Pointes, including: patients with a baseline QTcF > 470ms, personal or famiily history of long QT syndrome, or concomitant medications known to prolong the QT interval, hypokalemia, hypocalcaemia, or hypomagnesemia.
  • Pregnant or nursing (lactating) women.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals +41613241111
United States,   Argentina,   Australia,   Austria,   Bulgaria,   Canada,   China,   Colombia,   France,   Germany,   India,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Russian Federation,   Spain,   Thailand,   Turkey,   United Kingdom
 
 
NCT02180217
CLCI699C2301
2013-004766-34 ( EudraCT Number )
No
Not Provided
Not Provided
Not Provided
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP