A Phase II trial to assess the efficacy and safety of pasireotide s.c. alone or in combination with cabergoline in patients with Cushing’s disease
- Conditions
- Cushing's diseaseMedDRA version: 18.1 Level: LLT Classification code 10011651 Term: Cushing's disease System Organ Class: 100000004860Therapeutic area: Diseases [C] - Hormonal diseases [C19]
- Registration Number
- EUCTR2013-002170-49-NL
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 64
1. Adult patients with confirmed diagnosis of ACTH-dependent Cushing’s disease
2. Patients with de novo Cushing’s disease can be included only if they are not considered candidates for pituitary surgery
3. Male or female patients aged 18 years or greater
4. Karnofsky performance status = 60 (i.e. requires occasional assistance, but is able to care for most of their personal
needs)
5.Patients on medical treatment for Cushing’s disease the following washout periods must be completed before
screening assessments are performed
6.Patients have been on pasireotide in the past but discontinued
because of lack of efficacy are also allowed to enter Group 1. Patients treated with pasireotide subcutaneously must have been discontinued from the treatment for at least 4 weeks before
screening. Patients treated with pasireotide LAR must have been
discontinued from the treatment for at least 12 weeks before screening.
7. Patients who meet any one of the following criteria:
* They are naive to pasirotide
* They have recieved pasireotide in the past and have been discontinued because of lack of efficacy (2 weeks of washout prior to screening for patients treated with pasireotide subcutaneously and 12 weeks of washout prior to screening for patients treated with pasireotide LAR)
* Patients who are on maximal tolerated dose but have not achieved biochemical control
8. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, if they are using
highly effective methods of contraception during dosing and for 30 days after stopping study medication.
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 64
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8
Exclusion criteria for Group 1 and Group 2:
1. Patients with compression of the optic chiasm causing any visual field defect that requires surgical intervention
2. Diabetic patients with poor glycemic control as evidenced by HbA1c >8%
3. Patients with risk factors for torsade de pointes, i.e. patients with a baseline QTcF >450 ms in males, and > 460 ms in
females. hypokalemia, hypomagnesaemia, uncontrolled hypothyroidism, family history of long QT syndrome, or concomitant medications known to prolong QT interval.
4. Patients with clinically significant valvular disease.
5. Patients with Cushing’s syndrome due to ectopic ACTH secretion
6. Patients with hypercortisolism secondary to adrenal tumors or nodular (primary) bilateral adrenal hyperplasia
7. 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
8. Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis, or patients with ALT/AST > 2 X ULN, serum bilirubin >2.0 X ULN
9. Patients with serum creatinine >2.0 X ULN
10. Patients with WBC <3 X 10e9/L; Hb 90% < LLN; PLT <100 X 10e9/L
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 who are hypothyroid and not on adequate replacement therapy
13. Patients with symptomatic cholelithiasis
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> Main Objective: To evaluate the overall efficacy of the treatment regimen of pasireotide alone or in combination with cabergoline in patients in patients with Cushings disease.<br> ;<br> Secondary Objective: Assess the changes in mUFC from baseline to study end at each scheduled visit where UFC is measured<br> Assess overal efficacy of pasireotide alone or in combination with cabergoline as measured by normal mUFC levels at each scheduled visit<br> ;<br> Primary end point(s): mUFC :<br> Proportion of patients who attain mUFC = 1.0 x ULN at week 35 with pasireotide alone<br> or in combination with cabergoline <br> <br> ;<br> Timepoint(s) of evaluation of this end point: at week 35 <br> <br> <br> <br>
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): 1. Percentage change in mUFC from baseline to study end at each scheduled visit when UFC is measured <br> 2. Proportion of patients attain mUFC = 1.0 x ULN as assessed at each scheduled visit when UFC is measured <br> 3. Proportion of patients who attain mUFC = 1.0 x ULN or have at least 50% reduction from baseline in mUFC as assessed at each scheduled visit when UFC is measured<br> ;<br> Timepoint(s) of evaluation of this end point: at weeks 0, 4, 8, 13, 17, 22, 26, 31, 35<br> <br>