A Randomized, Multicenter, Phase II Study to Investigate Efficacy and Safety of ITF2984 in Acromegalic Patients
Overview
- Phase
- Phase 2
- Intervention
- Octreotide
- Conditions
- Acromegaly
- Sponsor
- Italfarmaco
- Enrollment
- 48
- Locations
- 26
- Primary Endpoint
- effect of treatment on GH and IGF-1
- Status
- Completed
- Last Updated
- 9 years ago
Overview
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.
Investigators
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.
Arms & Interventions
Octreotide
Octreotide 100 mcg sc three times daily (t.i.d) for 4 weeks
Intervention: Octreotide
ITF2984 500 mcg
ITF2984 500 mcg sc twice a day (b.i.d) for 4 weeks
Intervention: ITF2984 500 mcg
ITF2984 1000 mcg
ITF2984 1000 mcg sc b.i.d for 4 weeks
Intervention: ITF2984 1000 mcg
ITF2984 2000 mcg
ITF2984 2000 mcg sc b.i.d for 4 weeks
Intervention: ITF2984 2000 mcg
Outcomes
Primary Outcomes
effect of treatment on GH and IGF-1
Time Frame: 4 weeks
To investigate the effect of treatment on GH and IGF-1 concentrations
Secondary Outcomes
- reduction in (random) GH < 1.0 mcg/l and/or normalization of IGF-1(4 weeks)
- dose-response effect of ITF2984 on GH and IGF1 circulating levels(4 weeks)
- reduction of GH to no more than 2.5 mcg/l and/or normalization of IGF-1(4 weeks)
- signs and symptoms of acromegaly(4 weeks)
- PK profile of ITF2984 and Octreotide(4 weeks)
- effects of ITF2984 vs Octreotide on GH and IGF1 circulating levels(4 weeks)