Endocrine Abstracts

Introduction: The present study is designed to evaluate the efficacy and safety of pasireotide-long-acting release (LAR) in patients with acromegaly inadequately controlled after ≧3 mo treatment with the maximal approved doses of first-generation SSAs.

Methods: Phase IIIb, multicentre, single-arm, open-label study.

Patients: Adults (N~112) with inadequately controlled acromegaly (mean GH>1 μg/l and IGF-1>1.3xULN) despite receiving octreotide-LAR (30 mg/40 mg depending on the country) or lanreotide-ATG (120 mg) for ≧3 mo.

Design: Run-in phase (≧3 mos): patients on octreotide-LAR 30 mg despite the availability of the 40 mg dose at the time of screening will enter a run-in receiving three injections of octreotide-LAR 40 mg/28 day. Core phase (wk0-36): starting dose of pasireotide-LAR: 40 mg/28 day. GH and IGF-1 evaluated every 12 week and dose increased to 60 mg/28 day in uncontrolled patients (mean GH>1.0 μg/l and/or IGF-1>ULN) if no tolerability issues. Dose will remain unchanged in biochemically controlled patients. Dose decrease is permitted for safety reasons. During the extension phase (wk36–72), concomitant medications used to treat acromegaly are allowed if patients are uncontrolled on pasireotide 60 mg/28 day. Safety and tolerability will be assessed throughout the study.

Endpoints: Primary: proportion of patients with GH<1 μg/l and IGF-1<ULN at wk36; supporting analyses for primary endpoint will be performed in two patient sub-groups by mean GH level at screening (GH: 1–2.5 μg/l, GH>2.5 μg/l). Secondary: change in mean GH (five-point profile over a 2-h period), IGF-1xULN from study baseline to wk36; proportion of patients overall and by mean GH level at screening with GH<1 μg/l and IGF-1<ULN at wk12 and 24; GH<1 μg/l alone, IGF-1<ULN alone at wk12, 24 and 36, safety and health-related quality of life.

Conclusions: This study will evaluate efficacy and safety of pasireotide-LAR in patients with inadequately controlled acromegaly after ≧3 mo treatment with maximal approved doses of first-generation SSAs. In particular, a new patient population with GH 1–2.5 μg/l not studied in the PAOLA study will be evaluated.

Disclosure: This work was supported by Novartis.