a study to find out if a drug pasireotide used alone or used with cabergoline together is safe and beneficial for patients with Cushing’s disease(Cushing’s disease is a condition where the pituitary gland releases too much adrenocorticotropic hormone (ACTH).
- Conditions
- Health Condition 1: null- Cushings disease
- Registration Number
- CTRI/2014/06/004700
- Lead Sponsor
- ovartis Healthcare Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 6
1. Written informed consent obtained prior to any screening procedures.
2. Adult patients with confirmed diagnosis of ACTH-dependent Cushing’s disease as evidenced by all of the following:
a. The mean of three 24-hour urine samples collected within 2 weeks greater than 1xULN with 2 out of 3 samples greater than ULN
b. Morning plasma ACTH within the normal or above normal range
c. Either MRI confirmation of pituitary adenoma greater than 6 mm, or inferior petrosal sinus
gradient greater than 3 after CRH stimulation for those patients with a tumor less than or equal to 6 mm (If IPSS had previously been performed without CRH (e.g. with DDAVP), then a
central to peripheral pre-stimulation gradient greater than 2 is required. If IPSS had not
previously been performed, IPSS with CRH stimulation is required.). For patients who have had prior pituitary surgery, histopathology confirming an ACTH staining adenoma
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. Karnofsky performance status = 60 (i.e. requires occasional assistance, but is able to care for most of their personal needs)
5. 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. Highly effective contraception
methods include:
• 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
• 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
• 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.
• 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
<1%), 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 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.
Inclusion criteria for Group 1:
1. Patients on medical treatment for Cushing’s disease the following washout periods must
be completed before screening assessments are performed
• Inhibitors of steroidogenesis (ketoconazole, metyrapone): 1 week
• Pituitary directed agents: Dopamine agonists (bromocriptine, ca
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 greater than 8%
3. Patients with risk factors for torsade de pointes, i.e. patients with a baseline QTcF greater than 450 ms in males, and greater than 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 a known inherited syndrome as the cause for hormone over-secretion
(i.e. Carney Complex, McCune-Albright syndrome, MEN-1)
8. Patients who are hypothyroid and not on adequate replacement therapy
9. Patients with symptomatic cholelithiasis
10. 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
11. Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent
hepatitis, or patients with ALT/AST greater than 2 X ULN, serum bilirubin greater than 2 X ULN
12. Patients with serum creatinine greater than 2 X ULN
13. Patients with WBC less than 3 X 10 raised to e 9/L; Hb 90% less than LLN; PLT less than 100 X 10 raised to e 9/L
14. Patients who have a history of alcohol or drug abuse in the 6 month period prior to
receiving pasireotide
15. Patients who have participated in any clinical investigation with an investigational drug within 1 month prior to dosing
16. Patients with active malignant disease within the last five years (with the exception of
basal cell carcinoma or carcinoma in situ of the cervix)
17. Patients with the presence of active or suspected acute or chronic uncontrolled infection
18. Patients with a history of non-compliance to medical regimens or who are considered
potentially unreliable or will be unable to complete the entire study
19. Patients with presence of Hepatitis B surface antigen (HbsAg)
20. Patients with presence of Hepatitis C antibody test (anti-HCV)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. To evaluate the overall efficacy of the treatment regimen of pasireotide alone or in combination with cabergoline in patients who are pasireotide untreated at screening(Group1) <br/ ><br>2. To evaluate the efficacy of pasireotide in combination <br/ ><br>with cabergoline in patients treated with pasireotide at <br/ ><br>screening but still with uncontrolled mUFC (Group 2)Timepoint: 1. Proportion of patients who attain mUFC less than or equal to 1xULN at week 35 with pasireotide alone or in combination with cabergoline in Group 1 <br/ ><br>2. Proportion of patients who attain a mUFC less than or equal to 1xULN at week 17 with pasireotide in Group 2
- Secondary Outcome Measures
Name Time Method