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: 12.1 Level: LLT Classification code 10000599 Term: Acromegaly
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Male and female patients = 18 years of age •Patients with written informed consent prior to any study related activity •Patients with inadequately controlled acromegaly as defined by •a mean GH concentration of a 5-point profile over a 2-hour period > 2.5 µg/L and •sex- and age adjusted IGF-1 > 1.3 x upper limit of normal (ULN) •Patients treated with maximum indicated doses of octreotide LAR or lanreotide ATG for at least 6 months prior to randomization. The maximum indicated dose for octreotide LAR is 30 mg and for lanreotide ATG is 120 mg •Patients with diagnosis of pituitary micro- or macro adenoma. Patients can have been previously submitted to surgery 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: •Patients who have received pasireotide (SOM 230) prior to enrolment •Concomitant treatment with GHR-antagonist or dopamine agonists unless concomitant treatment was discontinued 8 weeks prior to randomization (8-week wash-out period) •Patients with compression of the optic chiasm causing acute clinically significant visual field defects •Patients who require a surgical intervention for relief of any sign or symptom associated with tumor compression •Patients who have received pituitary irradiation within 10 years prior to randomization •Patients who have undergone major surgery/surgical therapy for any cause within 4 weeks prior to randomization •Patients who are hypothyroid and not adequately treated with a stable dose of thyroid hormone replacement therapy •Diabetic patients whose blood glucose is poorly controlled as evidenced by HbA1C >8% at screening. Patients with a known history of impaired fasting glucose or diabetes mellitus with HbA1c 450 msec •History of syncope or family history of idiopathic sudden death •Sustained or clinically significant cardiac arrhythmias •Risk factors for Torsades de Pointes such as uncorrected hypokalemia, uncorrected hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia or high-grade AV block. •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 •Concomitant medication(s) known to increase the QT interval •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 bilirubin > 2 x ULN, serum albumin 2.0 x ULN •Patients with WBC <3 x 109/L; Hgb < 90% LLN; PLT <100 x 109/L •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 •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 •Known hypersensitivity to somatostatin analogues or any other component of pasireotide LAR •Patients with active malignant disease within the last five years (with the exception of basal cell carcinoma or carcinoma in situ of the cervix) •Patients with the presence of active or suspected acute or chronic uncontrolled infection •Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method of birth control. If a woman is participating in the trial then one form of contraception is sufficient (pill or diaphragm) and the p
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the proportion of patients achieving biochemical control defined as mean GH levels 25% assessed by pituitary MRI at 24 weeks, To assess the effect of pasireotide LAR (40 mg and 60 mg separately) vs continuing the same treatment on •the percent change of tumor volume from baseline to 24 weeks, •the time to response, •on the symptoms of acromegaly, To assess the: •health-related quality of life using the AcroQoL instrument •overall safety and tolerability of pasireotide LAR 40 mg and LAR 60 mg. •pharmacokinetics of pasireotide LAR 40 mg and LAR 60 mg ;Primary end point(s): Primary efficacy endpoint The proportion of patients with a reduction of mean GH levels to < 2.5 µg/L and normalization of sex- and age-adjusted IGF-1 at 24 weeks Safety endpoints Adverse events, physical examinations including vital signs, gallbladder ultrasound, ECGs, hematology (including coagulation parameters), blood chemistry (including fasting blood glucose, HbA1c, liver and thyroid function tests), serum cortisol, plasma ACTH, injection site reactions, urinalyses | — |
Countries
Belgium, France, Germany, Italy, Norway, Poland, Spain, United Kingdom
Outcome results
None listed