safety and efficacy of pasireotide s.c. in patients with Cushing's disease
- Conditions
- Cushing’s diseaseMedDRA version: 18.1Level: LLTClassification code 10011651Term: Cushing's diseaseSystem Organ Class: 100000004860Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2010-024165-44-CZ
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 200
Patients eligible for inclusion in this study have to meet all of the following criteria:
1.Written informed consent obtained prior to any screening procedures
2.Male or female patients aged 18 years or greater
3.Patients with confirmed diagnosis of Cushing’s disease as evidenced by
•mean urinary free cortisol of three 24-hour urine samples collected during the 2-week screening period above the upper limit of the laboratory normal range
•morning plasma ACTH within the normal or above normal range
•either MRI confirmation of pituitary adenoma (greater than or equal to 0.6 cm), or inferior petrosal sinus gradient >3 after CRH stimulation for those patients with a microadenoma less than 0.6 cm*, or 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)
4.Patients with de novo Cushing’s disease must not be considered as candidates for pituitary surgery (i.e. poor surgical candidates, surgically unapproachable tumors, patients with no visible pituitary tumor, patients who refuse to have surgical treatment)
5.Karnofsky performance status >60 (i.e. requires occasional assistance, but is able to care for most of this personal needs)
6.For patients on previous medical treatment for Cushing’s disease the following washout periods must be completed before screening assessments are performed
•Inhibitors of steroidogenesis (ketoconazole, metyrapone, rosiglitazone): 1 week
•Dopamine agonists (bromocriptine, cabergoline): 4 weeks
•Mitotane: 6 months
•Octreotide LAR and Lanreotide autogel: 8 weeks
•Lanreotide SR: 4 weeks
•Octreotide (immediate release formulation): 1 week
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 190
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
Patients eligible for this study must not meet any of the following criteria:
1.Radiotherapy of the pituitary <4 weeks before screening or patient who has not recovered from side effects
2.Patients with compression of the optic chiasm causing acute clinically significant visual field defect
3.Patients with Cushing’s syndrome due to ectopic ACTH secretion
4.Patients with hypercortisolism secondary to adrenal tumors or nodular (primary) bilateral adrenal hyperplasia
5.Patients who have a known inherited syndrome as the cause for hormone over secretion (i.e. Carney Complex, McCune-Albright syndrome, MEN-1)
6.Patients with a diagnosis of glucocorticoid-remedial aldosteronism (GRA)
7.Patients who have undergone major surgery within 1 month prior to screening
8.Patients with known gallbladder or bile duct disease, acute or chronic pancreatitis (patients with asymptomatic cholelithiasis and asymptomatic bile duct dilation can be included)
9.Diabetic patients whose blood glucose is poorly controlled as evidenced by HbA1C >8%
10.Patients who have clinically significant impairment in cardiovascular function or are at risk thereof, as evidenced by
•congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, high grade AV block, history of acute MI less than one year prior to study entry
•QTcF >450 msec at screening
•History of syncope or family history of idiopathic sudden death
•Risk factors for Torsades de Pointes such as uncorrected hypokalemia, uncorrected hypomagnesemia, cardiac failure
•Concomitant disease(s) that could prolong the QT interval such as autonomic neuropathy (caused by diabetes or Parkinson's disease), HIV,cirrhosis, uncontrolled hypothyroidism, concomitant medication(s) with known risk for TdPOther protocol-defined inclusion/exclusion criteria may apply
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To document the safety of pasireotide s.c. in patients with CD;Secondary Objective: To document:<br>-the efficacy of pasireotide s.c. in normalizing UFC at Week 12 and 24, separately<br>- the efficacy of pasireotide s.c. in achieving at least 50% reduction of UFC from baseline at Week 12 and 24, separately <br>- the changes in clinical signs and symptoms<br>- the changes in patient-reported outcome questionnaires (CushingQoL and WPAI-GH)<br>- the effects of pasireotide s.c. on the GH/IGF-I axis<br><br>Other secondary objectives may apply <br>Other secondary objectives may apply ;Primary end point(s): The proportion of patients having a drug-related adverse event that is recorded as grade 3 or 4 or as a serious adverse event.;Timepoint(s) of evaluation of this end point: Week 0, 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, 48
- Secondary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: • Baseline, week 12, 24 and 48 <br>• Baseline, week 12, 24 and 48 <br>• Baseline, week 12, 24 and 48<br> • Baseline, week 12, 24 and 48<br> • Baseline, week 12, 24 and 48 ;Secondary end point(s): The secondary end points are:<br>•proportion of patients with mean UFC = ULN at Week 12 and 24, separately<br>•proportion of patients achieving a reduction of mean UFC = 50% from baseline at Week 12 and 24, separately<br>•change from baseline to Week 12 and 24 in clinical signs and symptoms<br>•change from baseline to Week 12 and 24 in CushingQoL and WPAI-GH scores<br>•change from baseline to Week 12 and 24 in GH and IGF-I separately<br><br>Other secondary endpoints may apply.