phase III study to evaluate safety and efficacy of pasireotide LAR in patients with Cushing's disease

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2009-011128-70-DE
• Date of registration: 22/07/2011
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: phase III study to evaluate safety and efficacy of pasireotide LAR in patients with Cushing's disease
• Scientific title: A randomized, double-blind, multicenter, phase III study to evaluate the efficacy and safety of pasireotide LAR in patients with Cushing’s disease
• Date of first enrolment: 04/10/2011
• Target sample size: 162
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-011128-70
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Randomization to different doses of pasireotide 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): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Belgium, Brazil, Canada, China, Germany, Italy, Japan, Peru, Poland, Spain, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: Medizinscher Infoservice
• Affiliation: Novartis Pharma GmbH

• Name: Medizinscher Infoservice
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
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. Adult patients with confirmed diagnosis of ACTH-dependant Cushing’s disease as evidenced by all of the following:
a. The mean of three 24-hour urine samples collected within 2 weeks = 1.5 x ULN and = 5x ULN (as determined by the central lab of this study)
b. Morning plasma ACTH within the normal or above normal range
c. Confirmation of pituitary origin of excess ACTH by at least one of the following
three:
I. History of MRI confirmation of pituitary adenoma (greater than 6 mm) with
positive dynamic test (e.g. CRH or high dose dexamethasone suppression test)
Or
II. History of inferior petrosal sinus sampling in patients with a tumor less or equal
than 6 mm that meet any of the following criteria with either CRH or DDAVP
(desmopressin) stimulation:
• Central to peripheral ACTH ratio = 2 at baseline, or
• Central to peripheral ACTH ratio = 3 after stimulation by either CRH or DDAVP
(desmopressin)
Or
III. Prior pituitary

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. Confirmation that pseudo-Cushing’s is excluded for patients with mUFC = 3 x ULN (local lab analysis is sufficient) by at least 2 of 3 tests being abnormal (low-dose dexamethasone suppression test, dexamethasone-CRH test or late salivary or serum cortisol), unless there is histopathologic evidence for an ACTH staining pituitary tumor.
5. Male or female patients aged 18 years or greater
6. Karnofsky performance status = 60 (i.e. requires occasional assistance, but is able to care for most of their personal needs)
7. For patients on medical treatment for Cushing’s disease the following washout periods must be completed before screening assessments are performed
a. Inhibitors of steroidogenesis (ketoconazole, metyrapone): 1 week
b. Pituitary directed agents: Dopamine agonists (bromocriptine, cabergoline) and PPAR? agonists (rosiglitazone or pioglitazone): 4 weeks
c. Octreotide LAR, Lanreotide SR and Lanreotide autogel: 14 weeks
d. Octreotide (immediate release formulation): 1 week
e. Progesterone receptor antagonist (mifeprsistone): 4 weeks
8. Patients with a known history of impaired fasting glucose or DM may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the study and adjusted as necessary.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients eligible for this study must not meet any of the following criteria:
1. Patients who are considered candidates for surgical treatment at the time of study entry
2. Patients who have received pituitary irradiation within the last ten years prior to visit 1
3. Patients who have had any previous pasireotide treatment
4. Patients who have been treated with mitotane during the last 6 months prior to Visit 1
5. Patients with compression of the optic chiasm causing any visual field defect that requires surgical intervention
6. Diabetic patients with poor glycemic control as evidenced by HbA1c >8%
7. Patients with risk factors for torsade de pointes, i.e. patients with a baseline QTcF >470 ms, hypokalemia, hypomagnesemia, uncontrolled hypothyroidism, family history of long QT syndrome, or concomitant medications known to prolong QT interval
8. History of HIV infection, including a positive HIV test result (Elisa and Western blot). An HIV test will not be required, however, previous medical history will be reviewed
9. Patients with Cushing’s syndrome due to ectopic ACTH secretion
10. Patients with hypercortisolism secondary to adrenal tumors or nodular (primary) bilateral adrenal hyperplasia
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 with a diagnosis of glucocorticoid-remedial aldosteronism (GRA)
13. Patients who are hypothyroid and have clinical symptoms of hypothyroidism despite adequate replacement therapy
14. Patients who have undergone major surgery within 1 month prior to starting the study
15. Patients with symptomatic cholelithiasis
16. Patients with abnormal coagulation (PT or PTT elevated by 30% above normal limits)
17. Patients receiving anticoagulants that affect PT or PTT
18. 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
19. Patients with hystory of liver disease such as cirrhosis, chronic active hepatitis B or C, or patients with ALT or AST more than 2 X ULN, baseline total bilirubin >1.5 X ULN
20. Patients with serum creatinine >2.0 X ULN,
21. Patients with WBC <3 X 109/L; Hgb 90% < LLN; PLT <100 X 109/L
22. Patients who have any current or prior medical condition that can interfere with the conduct of the study or the evaluation of its results in the opinion of the investigator or the sponsor’s medical monitor
Other exclusion criteria as per protocol may apply


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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Cushing's disease
MedDRA version: 19.0 Level: LLT Classification code 10011651 Term: Cushing's disease System Organ Class: 100000004860

Intervention(s)

Product Name: pasireotide
Product Code: SOM230
Pharmaceutical Form: Powder and solvent for suspension for injection
INN or Proposed INN: pasireotide
CAS Number: 396091-79-5
Current Sponsor code: SOM230
Other descriptive name: pasireotide pamoate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Name: pasireotide
Product Code: SOM230
Pharmaceutical Form: Powder and solvent for suspension for injection
INN or Proposed INN: pasireotide
CAS Number: 396091-79-5
Current Sponsor code: SOM230
Other descriptive name: pasireotide pamoate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Product Name: pasireotide
Product Code: SOM230
Pharmaceutical Form: Powder and solvent for suspension for injection
INN or Proposed INN: pasireotide
CAS Number: 396091-79-5
Current Sponsor code: SOM230
Other descriptive name: pasireotide pamoate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Product Name: pasireotide
Product Code: SOM230
Pharmaceutical Form: Powder and solvent for suspension for injection
INN or Proposed INN: pasireotide
CAS Number: 396091-79-5
Current Sponsor code: SOM230
Other descriptive name: pasireotide pamoate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-

Primary Outcome(s)

Primary end point(s): Proportion of patients that attain a mUFC = 1.0 x ULN at Month 7 regardless of dose titration

Main Objective: To assess the efficacy of two Pasireotide LAR regimens (starting doses of 10 mg and 30 mg followed by up-titration if needed or continuation of the same dose) independently in patients with Cushing’s disease after 7 months of treatment regardless of up titration at Month 4

Secondary Objective: Key Secondary: To assess the efficacy of Pasireotide LAR 10 mg and 30 mg doses independently in patients with Cushing’s disease after 7 months of treatment who did not up titrate the dose of pasireotide at month 4.
Other secondary: Refer to Study protocol

Timepoint(s) of evaluation of this end point: Month 7

Secondary Outcome(s)

Secondary end point(s): Key secondary endpoint: Proportion of patients that attain a mUFC = 1.0 x ULN at Month 7 and had not had a dose increase at Month 4.
For Other endpoint: refer to study protocol

Timepoint(s) of evaluation of this end point: Month 7

Secondary ID(s)

2009-011128-70-GB

CSOM230G2304

Source(s) of Monetary Support

Novartis Pharma Services