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

• Register: EUCTR
• Last refreshed on: 10 December 2019
• Main ID: EUCTR2013-002170-49-GR
• Date of registration: 24/01/2014
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 29/01/2014
• Target sample size: 128
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002170-49
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Bulgaria, Colombia, France, Germany, Greece, Hungary, India, Italy, Malaysia, Mexico, Netherlands, Spain, Turkey, United Kingdom, United States, Venezuela, Bolivarian Republic of

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion criteria for Group 1:
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.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.

Inclusion criteria for Group 2:
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 (e.g. poor surgical candidates, surgically unapproachable tumors, patients who refuse to have surgical treatment)
3.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.
4.Women of child-bearing potential, 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 128
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Cushing's disease

Intervention(s)

Product Name: pasireotide
Product Code: SOM230
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PASIREOTIDE DIASPARTATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.3-

Product Name: pasireotide
Product Code: SOM230
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PASIREOTIDE DIASPARTATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.6-

Product Name: pasireotide
Product Code: SOM230
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PASIREOTIDE DIASPARTATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.9-

Trade Name: Dostinex
Product Name: Cabergoline
Pharmaceutical Form: Tablet
Other descriptive name: CABERGOLINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0,5-

Primary Outcome(s)

Main Objective: 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)
• To evaluate the efficacy of pasireotide in combination with cabergoline in patients treated with pasireotide at screening but still with uncontrolled mUFC (Group 2)

Secondary Objective: Assess the changes in mUFC from baseline to study end at each scheduled visit where UFC is measured in Group 1 and Group 2 patients, separately.

Assess overall efficacy of pasireotide alone or in combination with cabergoline as measured by normal mUFC levels at each scheduled visit in Group 1 and Group 2, separately.

Timepoint(s) of evaluation of this end point: at week 35 for group 1

at week 17 for group 2

Primary end point(s): mUFC :
- Proportion of patients who attain mUFC = 1.0 x ULN at week 35 with pasireotide alone
or in combination with cabergoline in Group 1

- Proportion of patients who attain a mUFC = 1.0 x ULN at week 17 with pasireotide with combination of cabergoline in Group 2

Secondary Outcome(s)

Secondary end point(s): 1. Percentage change in mUFC from baseline to study end at each scheduled visit when UFC is
measured
2. Proportion of patients attain mUFC = 1.0 x ULN as assessed at each scheduled visit when UFC is measured
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

Timepoint(s) of evaluation of this end point: at weeks 0, 4, 8, 13, 17, 22, 26, 31, 35 for group 1

Secondary ID(s)

2013-002170-49-DE

CSOM230B2411

Ethics review

Status: Approved
Approval date:
Contact: