Phase II Study With ITF2984 in Acromegalic Patients

NCT ID: NCT02111044

Last Updated: 2016-06-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2016-02-29

Brief Summary

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.

Detailed Description

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.

Conditions

Acromegaly

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Octreotide

Octreotide 100 mcg sc three times daily (t.i.d) for 4 weeks

Group Type: ACTIVE_COMPARATOR

Octreotide

Intervention Type: DRUG

octreotide 100 mcg sc t.i.d. for 4 weeks

ITF2984 500 mcg

ITF2984 500 mcg sc twice a day (b.i.d) for 4 weeks

Group Type: EXPERIMENTAL

ITF2984 500 mcg

Intervention Type: DRUG

ITF2984 500 mcg sc b.i.d for 4 weeks

ITF2984 1000 mcg

ITF2984 1000 mcg sc b.i.d for 4 weeks

Group Type: EXPERIMENTAL

ITF2984 1000 mcg

Intervention Type: DRUG

ITF2984 1000 mcg sc b.i.d for 4 weeks

ITF2984 2000 mcg

ITF2984 2000 mcg sc b.i.d for 4 weeks

Group Type: EXPERIMENTAL

ITF2984 2000 mcg

Intervention Type: DRUG

ITF2984 2000 mcg sc b.i.d for 4 weeks

Interventions

Octreotide

octreotide 100 mcg sc t.i.d. for 4 weeks

Intervention Type: DRUG

ITF2984 500 mcg

ITF2984 500 mcg sc b.i.d for 4 weeks

Intervention Type: DRUG

ITF2984 1000 mcg

ITF2984 1000 mcg sc b.i.d for 4 weeks

Intervention Type: DRUG

ITF2984 2000 mcg

ITF2984 2000 mcg sc b.i.d for 4 weeks

Intervention Type: DRUG

Other Intervention Names

somatostatin analog; somatostatin analog; somatostatin analog; somatostatin analog

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Italfarmaco

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paolo Bettica, MD

Role: STUDY_DIRECTOR

Italfarmaco

Locations

St. Anne University Hospital

Brno, , Czechia

University Hospital Hradec Kralove

Hradec Králové, , Czechia

Université Hôpital Bicêtre

Le Kremlin-Bicêtre, , France

Hôpital de la TIMONE

Marseille, , France

Az MH Honvédkórház

Budapest, , Hungary

Semmelweis University

Budapest, , Hungary

University of Pecs

Pécs, , Hungary

University of Szeged

Szeged, , Hungary

Presidio Ospedaliero di Montichiari

Brescia, , Italy

Policlinico G. Martino

Messina, , Italy

Fondazione Policlinico IRCCS

Milan, , Italy

IRCCS Ospedale San Raffaele

Milan, , Italy

Università Federico II

Napoli, , Italy

Università di Pisa

Pisa, , Italy

San Giovanni Battista Molinette

Torino, , Italy

Leiden University Medical Center

Leiden, , Netherlands

Erasmus Medisch Centrum

Rotterdam, , Netherlands

University Children's Hospital of Cracow

Krakow, , Poland

Klinika Endokrynologii Centrum Medycznego Kształcenia Podyplomowego

Warsaw, , Poland

Samodzielny Publiczny Szpital Kliniczny

Wroclaw, , Poland

Institutul de Endocrinologie C.I.Parhon, Sectia clinica de endocrinologie II

Bucharest, , Romania

Institutul de Endocrinologie C.I.Parhon, Sectia clinica de endocrinologie I

Bucharest, , Romania

Institutul de Endocrinologie C.I.Parhon, Sectia clinica de endocrinologie VI

Bucharest, , Romania

Clinical Center of Serbia

Belgrade, , Serbia

Clinical center of Nis

Niš, , Serbia

Complejo Hospitalario Universitario de Santiago de Compostela

Santiago de Compostela, , Spain

Countries

Czechia; France; Hungary; Italy; Netherlands; Poland; Romania; Serbia; Spain

Other Identifiers

DSC/13/2984/05

Identifier Type: -

Identifier Source: org_study_id