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: 19.0 Level: LLT Classification code 10011651 Term: Cushing's disease System Organ Class: 100000004860
- Registration Number
- EUCTR2013-002170-49-BE
- 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
Inclusion criteria for Group 1
1.Written informed consent obtained prior to any screening procedures.
2.Adult patients with confirmed diagnosis of ACTH-dependent Cushing's
disease
3.Patients with de novo Cushing's disease can be included only if they
are not considered candidates for pituitary surgery
4.Male or female patients aged 18 years or greater
5.Karnofsky performance status = 60
6.Patients on medical treatment for Cushing's disease following washout
periods
7.Patients have been on pasireotide in the past but discontinued because
of lack of efficacy are also allowed to enter Group 1.
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.
9.Male participants in the trial must agree to use a condom during
intercourse, and not to father a child during the study and for the period
of 30 days following stopping of the study treatment.
Inclusion criteria for Group 2
1.Written informed consent obtained prior to any screening procedures.
2.Adult patients with confirmed diagnosis of ACTH-dependent Cushing's
disease
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.Patients currently treated with maximal tolerated doses of pasireotide
for at least 8 weeks at the time of screening but have not achieved
biochemical control. These patients will enter the study starting
combination therapy.
5.Male or female patients aged 18 years or greater
6.Karnofsky performance status = 60.
7. Patients who meet any one of the following criteria:
• They are naïve to pasireotide
• They have received 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. Male participants in the trial must agree to use a condom during
intercourse, and not to father a child during the study and for the period
of30 days following stopping of the study treatment.
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) no
F.1.3.1 Number of subjects for this age range
Group 1 and Group 2 exclusion criteria
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 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 > 2 X ULN,
serum bilirubin >2.0 X ULN
12.Patients with serum creatinine >2.0 X ULN
13.Patients with WBC <3 X 10e9/L; Hb 90% < LLN; PLT <100 X 10e9/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)
21.Patients with severe hepatic impairment (Child Pugh C) and
hypersensitivity to pasireotide or cabergoline
22.Patients with lung, pericardial, and retroperitoneal fibrosis; gastroduodenal
ulcer or digestive haemorrhage, galactose intolerance,
Parkinson's disease, uncontrolled hypertension and Raynaud's
syndrome.
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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<br> alone or in combination with cabergoline in patients with Cushing's<br> disease<br> ;<br> Primary end point(s): Proportion of patients who attain mUFC = 1.0 x ULN at week 35 with<br> pasireotide alone or in combination with cabergoline<br> ;<br> Timepoint(s) of evaluation of this end point: at week 35<br> ;<br> Secondary Objective: Assess the changes in mUFC from baseline to study end at each<br> scheduled visit where UFC is measured<br> Assess overall efficacy of pasireotide alone or in combination with<br> cabergoline as measured by normal mUFC levels at each scheduled visit<br>
- Secondary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: at weeks 0, 4, 8, 13, 17, 22, 26, 31, 35;<br> Secondary end point(s): 1. Percentage change in mUFC from baseline to study end at each<br> scheduled visit when UFC is<br> measured<br> 2. Proportion of patients attain mUFC = 1.0 x ULN as assessed at each<br> scheduled visit when UFC is measured<br> 3. Proportion of patients who attain mUFC = 1.0 x ULN or have at least<br> 50% reduction from baseline in mUFC as assessed at each scheduled<br> visit when UFC is measured<br>