E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000599 |
E.1.2 | Term | Acromegaly |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to compare 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 (sex and age related) between the two treatment groups at 6 months. |
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E.2.2 | Secondary objectives of the trial |
Compare the effect of pasireotide LAR vs. octreotide LAR: •on reduction of GH to <2.5 µg/L alone at 6 months • on tumor volume at 6 months •on normalization of IGF-1 alone at 6 months •on symptoms of acromegaly, specifically: ring size, headache, fatigue, perspiration, paresthesias, osteoarthralgia at 6 months •on health related quality of Life at 6 months •on PRL levels at 6 months
Compare the overall safety and tolerability of pasireotide LAR vs. octreotide LAR at 6 months Assess pasireotide and octreotide plasma exposure (trough concentrations)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Male or female patients aged between 18 and 80 years. •Patients with active acromegaly demonstrated by •a lack of suppression of GH nadir to < 1 μg/L after an oral tolerance test with 75 g of glucose (OGTT) or a mean GH concentration of a 5-point profile within a 2 hour time period of > 5 μg/L •an elevated circulating IGF-1 concentration (age and sex adjusted) •Patients who are medical treatment naïve after first surgery, or de-novo patients who present with a visual adenoma on MRI and who refuse pituitary surgery or for whom pituitary surgery is not indicated •Patients with a known history 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 •Patients for whom written informed consent to participate in the study has been obtained. Patients will need to provide their informed consent prior to starting any medication washout period
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E.4 | Principal exclusion criteria |
•Patients who are being or were treated with octreotide, lanreotide or dopamine agonists and patients who are currently treated with GH antagonists •De-novo patients not having an adenoma visible on MRI •Patients who have received pasireotide (SOM230) prior to randomization •Patients with compression of the optic chiasm causing any visual field defect •Patients who require a surgical intervention for relief of any sign or symptom associated with tumor compression •Patients who have undergone major surgery/surgical therapy for any cause within 1 month of visit 1 •Patients who have received radiotherapy (except pituitary irradiation) for any reason within 4 weeks of visit 1 must have recovered from any side effect of radiotherapy •Patients who have received pituitary irradiation within the last two years prior to visit 1 •Patients who are not biochemically euthyroid •Diabetic patients on antidiabetic medications whose fasting blood glucose is poorly controlled as evidenced by HbA1C >8% •Patients with symptomatic cholelithiasis •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) •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 six months preceding enrollment •Patients with risk factors for torsades de pointes, i.e. patients with a baseline QTc >480 ms, hypokalemia, hypomagnesemia, hypocalcemia, family history of long QT syndrome, and taking concomitant medications known to prolong 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 creatinine > 2.0 x ULN, serum bilirubin > 2 x ULN, serum albumin < 0.67 x LLN •Patients with WBC <3 x 109/L; Hgb <13 g/dL for males and <12 g/dL for females; PLT <100 x 109/L •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 •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 with condoms. If oral contraception is used in addition to condoms, the patient must have been practicing this method for at least three months prior to the enrollment and must agree to continue the oral contraceptive throughout the course of the study, and for three months after the study has ended. Male patients who are sexually active are required to use condoms during the study and for 3 months afterward •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 •Patients who have a history of alcohol or drug abuse in the 6-month period prior to receiving study drug •Patients who have participated in any clinical investigation with an investigational drug within 1 month prior to first dosing •Known hypersensitivity to somatostatin analogues or any other component of the pasireotide LAR or octreotide LAR formulations •Patients with additional 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 •Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will be unable to complete the entire study
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E.5 End points |
E.5.1 | 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 (sex and age related) at the end of the 6-month period. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |