E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the effect of treatment on GH and IGF-1 concentrations. |
|
E.2.2 | Secondary objectives of the trial |
- To investigate the biochemical response of ITF2984, defined as a reduction in (random) GH < 1.0 mcg/l and/or normalization of IGF-1.
- To investigate the biochemical response of ITF2984, defined as a reduction of GH to no more than 2.5 mcg/l and/or normalization of IGF-1.
- To evaluate variation of signs and symptoms of acromegaly at the end of each month of treatment in comparison with basal status.
- To investigate the pharmacokinetic (PK) profile of ITF2984 and Octreotide
- To compare the effects on GH and IGF1 circulating levels of different doses of ITF2984
- To compare the effects on GH and IGF1 circulating levels of ITF2984 and Octreotide |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed written informed consent.
- Patients with active acromegaly due to a pituitary adenoma. Active acromegaly should be confirmed by 2h five point mean GH level higher than 5 mcg/liter, lack of suppression of GH nadir to less than 1 mcg/liter after oral glucose tolerance test, and elevated IGF-1 for age and sex-matched controls.
- Patients aged between 18 to 80 years old inclusive.
- Patients treated with previous surgery and/or medical therapy or previously untreated (de novo). For patients who had previously received medical therapy for acromegaly a washout periods before study entry of 3 months for long-acting formulation of somatostatin analogs and 2 weeks for octreotide sc must be foreseen. Partial responder means a significant decrease (>50%), without achievement of control of GH and/or IGF-1 levels and/or >20 % tumor shrinkage after at least 6 months of SRL therapy.
- Patients with GH level and IGF-1 level for age and sex-matched controls out of range at baseline (GH at baseline > 2.5mcg/l). |
|
E.4 | Principal exclusion criteria |
- Patients undergone pituitary surgery within the prior 6 months.
- Patients who have received pituitary radiotherapy (within last 10 years).
- 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 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 with uncontrolled diabetes defined as having a fasting glucose > 150 mg/dL (8.3 mmol/L) or HbA1c ≥ 8% (Patients can be rescreened after diabetes is brought under adequate control).
- Patients who have had a significant cardiovascular disease in the three months prior to inclusion such as congestive heart failure (NYHA [New York Heart Association] class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, sustained clinically significant bradycardia, advanced heart block, or with a history of acute myocardial infarction.
− A marked baseline prolongation of QT/QTc interval i.e. a mean QT/QTc >450ms after 3 consecutive measurements at least 5 minutes apart.
− Patients with abnormal coaugulation, Prothrombin time (PT), activated partial thromboplastin time (PTT) elevated by 30% above normal limits.
- Symptomatic cholelithiasis, gallstone or chronic liver disease.
- Patients who have a history or presence at the moment of the screening visit of pancreatitis.
- Clinically significant GI, renal or hepatic disease (in the opinion of investigator).
- AST and/or ALT>2ULN.
- Severely reduced renal function (serum creatinine >2.0 mg/dl or 176μmol/L)
- Active HBV and/or active HCV infection.
- Patients who have a history of alcohol or drug abuse in the six-month period prior to the enrollment visit.
- Known hypothyroidism or hypocortisolism not adequately treated with a stable dose of thyroid or steroid hormone replacement therapy for at least the previous 3 months.
- Known hypersensitivity to any of the study medications, or components thereof or a history of drug or other allergy that in the opinion of the Investigator contraindicates their participation.
- Female patients who are pregnant or lactating, and female patient who are of childbearing potential or male patient with female partners of childbearing potential who do not accept the contraception requirements reported in the protocol (more details in section 4.3.2).
- Patients who have participated in any clinical investigation with an Investigational drug within 3 months before study entry.
- Current or recent (< 2 months) therapy with pegvisomant or cabergoline. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Change of GH and/or IGF-1 levels at the end of each month of treatment. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of each month of treatment |
|
E.5.2 | Secondary end point(s) |
- Number and percentage of patients with reduction of GH < 1.0 mcg/l and/or normalization of IGF-1 at the end of each month of treatment.
- Number and percentage of patients with reduction in GH <2.5 mcg/l and/or normalization of IGF-1 at the end of each month of treatment.
- Number and percentage of patients with improvement of signs and symptoms of acromegaly at the end of each month of treatment. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At the end of each month of treatment |
|
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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 | No |
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 | 2 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |