Study of efficacy and safety of pasireotide LAR in patients with inadequately controlled acromegaly.

• Register: EUCTR
• Last refreshed on: 19 November 2018
• Main ID: EUCTR2014-002630-31-HU
• Date of registration: 19/12/2014
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Study of efficacy and safety of pasireotide LAR in patients with inadequately controlled acromegaly.
• Scientific title: A phase IIIb multicenter, open-label, single arm study to evaluate the efficacy and safety of pasireotide in patients with acromegaly inadequately controlled with first generation somatostatin analogues
• Date of first enrolment: 25/03/2015
• Target sample size: 112
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002630-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• 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, Bulgaria, China, Colombia, France, Germany, Hungary, Italy, Mexico, Portugal, Sweden, Turkey, United Kingdom, Venezuela, Bolivarian Republic of

Key inclusion & exclusion criteria

Inclusion criteria:
1.Written informed consent must be obtained prior to any screening procedures
2. Male and female patients = 18 years of age
3. Patients with confirmed diagnosis of inadequately controlled acromegaly as evidenced by the following:
• A mean GH concentration of a 5-point profile over a 2-hour period = 1 µg/L and sex- and age-adjusted IGF-1 >1.3 x ULN
4. Patients treated with high dose of octreotide LAR (30 mg or 40 mg) or lanreotide ATG (120 mg) given as monotherapy for at least 3 months prior to screening (Visit 1)
• Note: Patients currently being treated with octreotide LAR 30 mg from countries where the octreotide LAR 40 mg dose is approved at the time of screening will start a run- in phase in which they will receive the 3 injections of octreotide LAR 40 mg before being evaluated for eligibility for the core phase of the study

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 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 22

Exclusion criteria:
1. Concomitant treatment with other medications known to reduce GH and or IGF-1, other than octreotide LAR or lanreotide ATG, unless discontinued 3 months prior to visit 1 (screening)
2. Patients with compression of the optic chiasm causing any visual field defect that requires surgical intervention
3. Diabetic patients with poor glycaemic control as evidenced by HbA1c >8% at Visit 1 for Group 2 and at both Visit 1 and Visit 5 for Group 1
4. Patients who are hypothyroid and not on adequate replacement therapy
5. Patients with symptomatic cholelithiasis and acute or chronic pancreatitis
6. Patients with clinically significant valvular disease
7. Patients with risk factors for torsade de pointes, i.e. patients with a baseline QTcF >450 ms in males, and >460 ms in females
8. Hypokalaemia, hypomagnesaemia, uncontrolled hypothyroidism, family history of long QT syndrome or concomitant medications with known risk of Torsades de pointes (TdP). Drugs with posible risk of TdP should be avoided whenever feasible.
9. 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
10. Concomitant disease(s) that could prolong the QT interval such as autonomic neuropathy (caused by diabetes or Parkinson’s disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure
11. Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis, or patients with ALT/AST > 2.0 X ULN, serum bilirubin >2.0 X ULN
12. Presence of Hepatitis B surface antigen (HbsAg) or Hepatitis C antibody test (anti-HCV)
13. Patients with serum creatinine >2.0 X ULN
14. Patients with WBC <3 X 109/L; Hb 90% < LLN; PLT <100 X 109/L
15. Patients with the presence of active or suspected acute or chronic uncontrolled infection
16. Patients who have undergone major surgery/surgical therapy for any cause within 4 weeks prior to visit 1 (screening)
17. Patients with active malignant disease within the last five years (with the exception of basal cell carcinoma or carcinoma in situ of the cervix)
18. Patients with abnormal coagulation (PT and/or APTT elevated by 30% above normal limits) or patients receiving anticoagulants that affect PT (prothrombin time) or APTT (activated partial thromboplastin time)
19. History of syncope or family history of idiopathic sudden death
20. History of immunocompromise, including a positive HIV test result (ELISA and Western blot). A HIV test will not be required; however, previous medical history will be reviewed
21. Known hypersensitivity to somatostatin analogues or any other component of the pasireotide LAR
22. Patients who have a history of alcohol or drug abuse in the 6 month period prior to receiving pasireotide
23. Patients who have given a blood donation (of 400 ml or more) within 2 months before receiving pasireotide
24. Patients who have participated in any clinical investigation with an investigational drug within 1 month prior to dosing
25. Patients with any current or prior medical condition that, in the judgment of the investigator may interfere with the conduct of the study or the evaluation of the study results
26. Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will be unable to complete the ent

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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Hormonal diseases [C19]

Acromegaly
MedDRA version: 19.0 Level: PT Classification code 10000599 Term: Acromegaly System Organ Class: 10014698 - Endocrine disorders

Intervention(s)

Product Name: pasireotide
Product Code: SOM230
Pharmaceutical Form: Powder and solvent for suspension for injection
INN or Proposed INN: pasireotide
Current Sponsor code: SOM230
Other descriptive name: PASIREOTIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Current Sponsor code: SOM230
Other descriptive name: PASIREOTIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Current Sponsor code: SOM230
Other descriptive name: PASIREOTIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-

Primary Outcome(s)

Secondary Objective: Core phase:
-assess the changes in mean GH and standardized IGF-1
-assess the proportion of patients achieving GH <1 µg/L and IGF-1 -assess the proportion of patients achieving GH <1µg/L or IGF-1 levels -evaluate the tolerability and safety profile of pasireotide LAR
-evaluate the effect of pasireotide LAR on HRQoL

Extension phase:
-assess the proportion of patients achieving IGF-1 -assess the proportion of patients achieving GH <1µg/L and IGF-1 concomitant medications used to treat acromegaly
-assess the proportion of patients achieving GH <1 µg/L by treatment with pasireotide LAR alone or with concomitant
medications used to treat acromegaly
-evaluate the long term tolerability and safety profile of pasireotide LAR
-evaluate the long term effect of pasireotide LAR on HRQoL

Main Objective: Primary objective:
- To evaluate the efficacy of pasireotide LAR in patients with acromegaly who are inadequately controlled with maximal approved doses of currently available somatostatin analogues

Supporting Analysis for Primary objective:
- To assess the proportion of patients achieving GH <1µg/L and IGF-1

Primary end point(s): - Proportion of patients who achieved GH <1µg/L and IGF-1
- Proportion of patients who achieved GH <1µg/L and IGF-1 2.5 µg/L

Timepoint(s) of evaluation of this end point: - at week 36.
- at week 36

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: - from study baseline to week 36
- at week 12 and 24 overall and at screening
- at week 12,24 and 36 overall and at screening
- from study enrollment until the safety follow-up
- from baseline to weeks 12, 24 and 36

For extension phase:
- at weeks 48, 60 and 72
- at weeks 48, 60 and 72
- at weeks 48, 60 and 72
- from study enrollment until the safety follow-up
- from baseline to week 72 and from week 36 to week 72

Secondary end point(s): - Changes in mean GH and standardized IGF-1 .
- Proportion of patients who achieved GH <1µg/L and IGF-1 - Proportion of patients who achieved GH <1µg/L or IGF-1 - Toxicity will be assessed using the National Cancer Institute-Common Toxicology Criteria Adverse Events version 4 (NCI-CTCAE v.4.03) and for laboratory assessments that include biochemistry, hematology, urinalysis; special safety assessments that include the regular monitoring and recording of blood glucose, insulin, HbA1c, GH and IGF-1, thyroid and liver function tests, gallbladder examinations and ECGs. Concomitant medications/Significant nondrug therapies will be assessed .
- Change in scores as measured by AcroQoL, EQ-5D-5L

For extension phase:
- Proportion of patients who achieved IGF-1 - Proportion of patients who achieved GH <1 µg/L and IGF-1 - Proportion of patients who achieved GH <1 µg/L by treatment with pasireotide LAR alone or with concomitant medications used to treat acromegaly
- Toxicity will be assessed using the National Cancer Institute-Common Toxicology Criteria Adverse Events version 4 (NCI-CTCAE v.4.03) and for laboratory assessments that include biochemistry, hematology, urinalysis; special safety assessments that include the regular monitoring and recording of blood glucose, insulin, HbA1c, GH and IGF-1, thyroid and liver function tests, gallbladder examinations and ECGs. Concomitant medications/Significant nondrug therapies will be assessed
- Change in scores as measured by AcroQoL, EQ-5D-5L

Secondary ID(s)

CSOM230C2413

Source(s) of Monetary Support

Novartis Pharma Services AG