Acromegaly is characterized by chronic hypersecretion of growth hormone (GH), clinical features comprise structural and functional changes occurring in practically all organs. Cardiovascular disease is the main reason for morbidity and increased mortality. MedDRA version: 9.1 Level: LLT Classification code 10000599 Term: Acromegaly
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients of at least 18 years of age 2. Patients with active acromegaly demonstrated by • a lack of suppression of GH nadir to 5 µg/L • elevated circulating IGF-1 concentration (age and sex adjusted) 3. a) Patients who have undergone one or more pituitary surgeries but have not been treated medically or b) de-novo patients who present with a visible pituitary adenoma on MRI and who refuse pituitary surgery or for whom pituitary surgery is contraindicated 4. Patients with a known history or new diagnisis of impaired fasting glucose or diabetes mellitus may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary (see Section 6.6.3) 5. Patients for whom written informed consent to participate in the study has been obtained. prior to any study related activity 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
Exclusion criteria: 1. Patients who are being or were treated with octreotide, lanreotide or dopamine agonists or GH antagonists with the exception of a single dose of short-acting ocreotide or short-acting dopamine agonists. In case of a single dose of short-acting ocreotide, the dose should not be used to predict the response to the ocreotide treatment. The single dose of short acting ocreotide or short-acting dopamine agonists should not be administered in the 3 days prior to randomization. 2. De-novo patients having a visible adenoma on MRI 3. Patients who have received pasireotide prior to randomization 4. Patients with compression of the optic chiasm causing any visual field defect 5. Patients who require a surgical intervention for relief of any sign or symptom associated with tumor compression for whom surgical intervention is indicated 6. Patients who have undergone major surgery/surgical therapy for any cause within 1 month of visit 1 7. Patients who have received radiotherapy (except for pituitary irradiation) for any reason within 4 weeks of visit 1 must have recovered from any side effect of radiotherapy 8. Patients who have received pituitary irradiation within the last ten years prior to visit 1 9. Patients who are hypothyroid and not adequately treated with stable doses of thyroid hormone replacement therapy 10. Diabetic patients on antidiabetic medications whose fasting blood glucose is poorly controlled as evidenced by HbA1c >8% 11. Patients with symptomatic cholelithiasis 12. 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) 13. Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the 6 months preceding enrollment 14. Patients with risk factors for torsade de pointes, i.e. patients with a baseline QTc > 450 ms, hypokalemia, hypomagnesemia, hypocalcemia, family history of long QT syndrome, and taking concomitant medications known to prolong QT interval 15. Patients with confirmed central hypothyroidism, central hypoadrenalism and diabetes insipidus, unless they are adequately treated with stable doses of hormone replacement therapy for a minimum of 3 months prior to study entry (first dose of study medication).Patients with confirmed central hypogonadism unless they are adequately treated with stable doses of hormone replacement therapy for a minimum of 3 months prior to study entry (first dose of study medication) except in cases where hormone replacement therapy is not indicated 16. Patients with liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis, or patients with ALT and/or AST more than 2 x ULN, serum creatinine > 2.0 x ULN, serum bilirubin > 2 x ULN, serum albumin < 0.67 x LLN 17. Patients with WBC <3 x 109/L; Hgb < 90%LLN; PLT <100 x 109/L 18. Patients who have any current or prior medical condition that may 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 19. Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method of birth control. Female patients must use barrier contraception w
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare the proportion of patients with a reduction of mean GH level to < 2.5µg/L and the normalization of IGF-1 to within normal limits (age and sex related) between the two treatment groups at 12 months.;Secondary Objective: assess the effect of pasireotide LAR vs. octreotide LAR on: •reduction of GH to <2.5 µg/L alone at 12 months •proportion of patients with a reduction of mean GH level to < 2.5 µg/L and on the normalization of IGF-1 to within normal limits (age and sex related) at months 6 and 9 •change from baseline in mean GH at 12 months •time to first achievement of mean GH < 2.5 µg/L and on normalization of IGF-1 to within normal limits (age and sex related) •symptoms of acromegaly, specifically: ring size, headache, fatigue, perspiration, paresthesias, osteoarthralgia at 12 months •health related quality of Life at 12 months •PRL levels at 12 months •duration of response for patients achieving reduction of mean GH level to<2.5µg/L and normalization of IGF-1 to within normal limits (age and sex related) at month 12 Compare the overall safety and tolerability of pasireotide LAR vs. octreotide LAR at 12 months Assess pasireotide and octreotide plasma exposure (trough concentrations) ;Primary end point(s): The proportion of patients with a reduction of mean GH level to <2.5 µg/L and the normalization of IGF-1 to within normal limits (age and sex related) at the end of the 12-month period. | — |
Countries
Belgium, Czech Republic, Denmark, France, Germany, Greece, Hungary, Italy, Netherlands, Poland, Portugal, Spain, Sweden, United Kingdom
Outcome results
None listed