A study to find out if LCI699 is safe and has beneficial effects in people who have Cushingâ??s disease (CD).CD is caused due to a adenoma (tumor) in the pitutiary gland (Brain) which results in excessive secretion of a hormone (ACTH) causing adrenal glands to secrete excessive cortisol.
- Conditions
- Health Condition 1: null- Cushings diseaseHealth Condition 2: E240- Pituitary-dependent Cushings disease
- Registration Number
- CTRI/2015/02/005579
- Lead Sponsor
- ovartis Healthcare Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 7
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 Cushingâ??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.
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 (5 half-lives) prior to screening.
6. Patients with de novo Cushingâ??s disease can be included only if they are not considered
candidates for surgery (e.g., poor surgical candidates, surgically unapproachable tumors,
patients who refuse to have surgical treatment, or surgical treatment is not available)
7. Patients with a history of pituitary irradiation can be included, provided that at least 3 years have elapsed from the time of radiation 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 Cushingâ??s disease. The following washout periods must be
completed before baseline efficacy assessments are performed:
a. Steroidogenesis inhibitors (ketoconazole, metyrapone): 1 week
b. Pasireotide s.c. or octreotide s.c. (immediate release formulation): 1 week
c. Dopamine agonists (e.g., cabergoline), or PPAR-gamma agonists (e.g., rosiglitazone,
pioglitazone): 4 weeks
d. Mifepristone or Lanreotide SR: 4 weeks
e. Octreotide LAR, Pasireotide LAR and Lanreotide Autogel®: 14 weeks
f. Mitotane: 6 months
g. Other experimental therapy: at least 5 half-lives or 30 days, whichever is longer
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 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, 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.
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. Highly effective contraception
methods include:
a. Total abstinence (when this is in line with the preferred and usual lifestyle of the
subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception.
b. Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy) or tubal ligation at least six weeks before taking study treatment. In
case of oophorectomy alone, only when the reproductive status of the woman has
been confirmed by follow up hormone level assessment.
c. Male sterilization (at least 6 months prior to screening). For female subjects on the
study the vasectomized male partner should be the sole partner for that subject.
d. Combination of any two of the following (a+b or a+c, or b+c):
a. Use of oral, injected, or implanted hormonal methods of contraception or other
forms of hormonal contraception that have comparable efficacy (failure rate less than 1 percent), for example hormone vaginal ring or transdermal hormone contraception
b. Placement of an intrauterine device IUD or intrauterine system IUS
c. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
In the case of use of oral contraception, women should have been stable on the same
pill for a minimum of 3 months before taking study treatment.
7. Fertile males, defined as all males physiologically capable of conceiving offspring
UNLESS they use a condom during intercourse while taking the study medication and for
1 week after stopping study medication and should not father a child in this period. A
condom is required to be used also by vasectomized men in order to prevent delivery of
the drug via seminal fluid.
8. Patients with compression of the optic chiasm, in order to exclude patients with a tumor
causing chiasmal compression requiring surgery.
9. Patients who have a known inherited syndrome as the cause for hormone over secretion
(i.e. Carney Comple
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To compare the complete response rate at the end of the 8-week <br/ ><br>period of randomized withdrawal (Week 34) between patients <br/ ><br>randomized to continued LCI699 therapy vs. placebo.Timepoint: Proportion of randomized patients in each arm with: mUFC â?¤ ULN at the <br/ ><br>end of 8 weeks of randomized withdrawal (Week 34), and were neither <br/ ><br>discontinued, nor had LCI699 dose increase above the level at week 26 <br/ ><br>during the randomized withdrawal period
- Secondary Outcome Measures
Name Time Method To assess the complete response rate at the end of individual <br/ ><br>dose-titration and treatment with LCI699 in the initial single-arm, <br/ ><br>open label period (Week 24).Timepoint: Proportion of enrolled patients with mUFC â?¤ ULN at Week 24 and had no <br/ ><br>dose increase above the level established at Week 12 between Week 13 <br/ ><br>and Week 24