A phase III study to evaluate the efficacy and safety of pasireotide LAR in patients with Cushing's disease
- Conditions
- Cushing's diseaseMedDRA version: 14.1Level: LLTClassification code 10011651Term: Cushing's diseaseSystem Organ Class: 10014698 - Endocrine disordersTherapeutic area: Diseases [C] - Hormonal diseases [C19]
- Registration Number
- EUCTR2009-011128-70-IT
- Lead Sponsor
- OVARTIS FARMA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 162
1. Written informed consent obtained prior to any screening procedures 2. Adult patients with confirmed diagnosis of ACTH-dependant Cushing`s disease as evidenced by all of the following: a. The mean of three 24-hour urine samples collected within 2 weeks = 1.5 x ULN and = 5x ULN (as determined by the central lab of this study) b. Morning plasma ACTH within the normal or above normal range c. Either MRI confirmation of pituitary adenoma > 6 mm, or inferior petrosal sinus gradient >3 after CRH stimulation for those patients with a tumor less than or equal to 6 mm*. For patients who have had prior pituitary surgery, histopathology confirming an ACTH staining adenoma. *if IPSS had previously been performed without CRH (e.g.with DDAVP), then a central to peripheral pre-stimulation gradient > 2 is required. If IPSS had not previously been performed, IPSS with CRH stimulation is required. 3. Patients with de novo Cushing`s disease can be included only if they are not considered candidates for pituitary surgery (e.g. poor surgical candidates, surgically unapproachable tumors, patients who refuse to have surgical treatment) 4. Confirmation that pseudo-Cushing`s is excluded for patients with mUFC = 3 x ULN (local lab analysis is sufficient) by at least 2 of 3 tests being abnormal (low-dose dexamethasone suppression test, dexamethasone-CRH test or late salivary or serum cortisol), unless there is histopathologic evidence for an ACTH staining pituitary tumor. 5. Male or female patients aged 18 years or greater 6. Karnofsky performance status = 60 (i.e. requires occasional assistance, but is able to care for most of their personal needs) 7. For patients on medical treatment for Cushing`s disease the following washout periods must be completed before screening assessments are performed a. Inhibitors of steroidogenesis (ketoconazole, metyrapone): 1 week b. Pituitary directed agents: Dopamine agonists (bromocriptine, cabergoline) and PPAR? agonists (rosiglitazone or pioglitazone): 4 weeks c. Octreotide LAR, Lanreotide SR and Lanreotide autogel: 14 weeks d. Octreotide (immediate release formulation): 1 week e. Progesterone receptor antagonist (mifeprsistone): 4 weeks 8. Patients with a known history of impaired fasting glucose or DM may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the study and adjusted as necessary.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 138
1.Patients who are considered candidates for surgical treatment at the time of study entry 2.Patients who have received pituitary irradiation within the last ten years prior to visit 1 3.Patients who have had any previous pasireotide treatment 4.Patients who have been treated with mitotane during the last 6 months prior to Visit 1 5.Patients with compression of the optic chiasm causing any visual field defect that requires surgical intervention 6.Diabetic patients on antihyperglycemic medications with poor glycemic control as evidenced by HbA1c >8% 7.Patients with risk factors for torsade de pointes, i.e. patients with a baseline QTcF >470 ms, hypokalemia,hypomagnesemia uncontrolled hypothyroidism, family history of long QT syndrome, or concomitant medications known to prolong QT interval 8.History of HIV infection, including a positive HIV test result (Elisa and Western blot). An HIV test will not be required, however, previous medical history will be reviewed 9.Patients with Cushing`s syndrome due to ectopic ACTH secretion 10.Patients with hypercortisolism secondary to adrenal tumors or nodular (primary) bilateral adrenal hyperplasia 11.Patients who have a known inherited syndrome as the cause for hormone over secretion (i.e. Carney Complex, McCune-Albright syndrome, MEN-1) 12.Patients with a diagnosis of glucocorticoid-remedial aldosteronism (GRA) 13.Patients who are hypothyroid and not on adequate replacement therapy 14.Patients who have undergone major surgery within 1 month prior to starting the study 15.Patients with symptomatic cholelithiasis 16.Patients with abnormal coagulation (PT or PTT elevated by 30% above normal limits) 17.Patients receiving anticoagulants that affect PT or PTT 18.Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, advanced heart block, history of acute MI less than one year prior to study entry or clinically significant impairment in cardiovascular function 19.Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis, or patients with ALT/AST more than 2 X ULN, serum bilirubin >2.0 X ULN 20.Patients with serum creatinine >2.0 X ULN, 21.Patients with WBC <3 X 109/L; Hgb 90% < LLN; PLT <100 X 109/L 22.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. 23.Female patients who are pregnant or lactating, or are of childbearing potential (defined as all women physiologically capable of becoming pregnant) and not practicing an effective method of contraception/birth control. Sexually active males must use a condom during intercourse while taking the drug and for 2 months after the last dose of study drug 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. Effective contraception methods include: • Use of oral, injected or implanted hormonal methods of contraception or • Placement of an intrauterine device (IUD) or intrauterine system (IUS) • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository • Total abstinence or • Patient sterilization (male or female) 24.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method