Phase II Study With ITF2984 in Acromegalic Patients
Phase II Study With ITF2984 in Acromegalic Patients
The purpose of this study is to investigate in acromegalic patients the effect of different
 doses of ITF2984 on GH and IGF-1 concentrations and to investigate safety and tolerability of
 three different doses of ITF2984.
The study will enroll patients with active acromegaly, de novo or partial responder to
 previous treatment with somatostatin analogues. 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, 2 weeks for octreotide sc, 2 months for
 pegvisomant and/or cabergoline must be foreseen.

 Each patient will be randomized and wll remain in the study for about 6 months, and they will
 attend a visit every two weeks.

 The patients will be treated for 4 months in a total, in particular every month of treatment
 will be followed by a washout period of 2 weeks.

 At each month of treatment the patients will receive one of the four treatment as reported
 below:

 Octreotide 100 mcg sc three times daily (t.i.d) for 4 weeks, ITF2984 500 mcg sc twice a day
 (b.i.d) for 4 weeks, ITF2984 1000 mcg sc b.i.d for 4 weeks, ITF2984 2000 mcg sc b.i.d for 4
 weeks. Patients will be randomized using a 4 way crossover design to receive ITF2984 or
 octreotide at each treatment month. Each patient will receive all of the four treatments
 overseen in this study.
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).

 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.

 -  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.