A 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
- Conditions
- Cushing's Disease10021112
- Registration Number
- NL-OMON47814
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 4
1. Adult patients with confirmed persistent of recurrent Cushings disease
2. Patients with history of pituary surgery must be at least 30 days
post-surgery
3. Patients that received glucocorticoid replacement therapy post-operatively
must have discontinued such therapy for at least one week prior screening
4. Patients with de de novo Cushing'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)
5. Patients with a history of pituitary irradiation can be included, provided
that at least 3 years have elapsed from the tie of radiation to the time of
enrollementinto this study.
6. Patients are permitted to washout current drug therapy to meet these entry
criteria if they have a known diagnosis of Cushing's disease.
1. Use of other investigational drugs at time of enrollment, or within 30 days
of time of enrollment
2. History hypertensitivity to LCI699 or other drugs of similar chemical classes
3. History of malignancy of any organ systems, 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 baseline QTcF > 470 ms, personal of familiy history of
long QT syndrome, or concomitant medications known to prolong the QT interval,
hypokalemia, hypocalcaemia or hypomagnesemia
5. Pregnant or nursing women
6. Women with child-bearing potential, unless tehy use higly effective
contraception
7. Fertile males, unless they use a condom during intercource.
8. Patients with the compression of the optic chiasm, in order to exclude
patients with a tumor caushing chiasmal compression requiring surgery
9. Patients who have a known inherited syndrome as the cuase for hormone over
secretion
10. Patients with Cushing's syndrome due to ectopec ATCH secretion or
ATCH-independent Cushing's syndrome.
11. Patients who have undergone major surgery within 1 month prior to screening
12. Hypertensive patients with uncontrolled blood pressure defined as SBP >
180and / or DBP > 100
13. Diabetic patients with a poorly controlled diabetes as evidenced by HbA1c >
9%
14. Patients who are not biochemically euthyroid
15. Patients who have a history of: congestive heart failure (NYHA Class III or
IV) 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.
16.Patients with moderate to severe renal impairment (estimated GFR < 60 mL/min
by the MDRD formula, or serum creatinine > 2.0 x ULN
17. Patients with liver disease such as cirrhosis, chronic active hepatitis, or
chronic persistenthepatitis, or patients with serum ALT/ASR > 3x ULN, or serum
bilirubin > 1.5 ULN.
18. 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
19. Patients who have a history of alcohol or drug abuse in the 6 month period
prior to the study treatment
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Proportion of patients with mUFC <= 1 ULN at week 24, and the dose of LCI699 is<br /><br>not increased above the level establised at the end of period 1</p><br>
- Secondary Outcome Measures
Name Time Method <p>Proportion of patients with mUFC <= 1 ULN at week 24, and the dose of LCI699 is<br /><br>increased above the level establised at the end of period 1</p><br>