| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with inadequately controlled acromegaly. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10000599 |
| E.1.2 | Term | Acromegaly |
|
| 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 |
| To compare the proportion of patients achieving biochemical control defined as mean GH levels < 2.5 μg/L and normalization of sex- and age-adjusted IGF-1 at 24 weeks with pasireotide LAR 40 mg and pasireotide LAR 60 mg separately versus continuing the same treatment with octreotide LAR 30 mg or lanreotide ATG 120 mg. |
|
| E.2.2 | Secondary objectives of the trial |
| To assess the effect of pasireotide LAR (40 mg and 60 mg separately) vs continuing the same treatment on the proportion of patients achieving: •biochemical control defined as mean GH levels < 2.5 μg/L and normalization of sex- and age-adjusted IGF-1 at 12 weeks, •GH levels < 2.5 μg/L at 12 and 24 weeks, •normal, sex- and age-adjusted IGF-1 at 12 and 24 weeks, •GH levels < 1 μg/L and normal, sex- and age-adjusted IGF-1 at 12 and 24 weeks, •GH levels < 1 μg/L at 12 and 24 weeks, •a tumor size reduction > 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. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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. |
|
| E.4 | Principal exclusion criteria |
| •Patients who have received pasireotide (SOM230) 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<8% may be included; however, blood glucose and anti diabetic treatment must be monitored closely throughout the trial and adjusted as necessary •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, advanced heart block or a history of acute myocardial infarction within the 6 months preceding randomization •Screening or baseline (predose) QTcF> 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 < 0.67 x LLN •Patients with serum creatinine> 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. PLEASE FOR THE OTHER 4 EXCLUSION CRITERIA SEE THE PROTOCOL. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The proportion of patients with a reduction of mean GH levels to < 2.5 μg/L and normalization of sex- and ageadjusted IGF-1 at 24 weeks. |
|
| 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 | No |
| 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 | Yes |
| 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 | No |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 41 |
| 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 |
|
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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