Pasireotide (
SOM230), a multireceptor-targeted
somatostatin analogue, has exhibited favorable safety/tolerability in several clinical studies. A long-acting-release (LAR) formulation of
pasireotide may offer advantages over the subcutaneous formulation. This randomized, open-label, Phase I study evaluated the safety, PK, and PD of
pasireotide LAR 20, 40, or 60 mg/month in patients with
acromegaly. Safety assessments and blood samples for PK and PD were taken at designated time points. Thirty-five patients were randomized and completed the study. Steady-state
pasireotide concentrations were achieved following three monthly
injections. Trough
pasireotide concentrations (ng/mL) 28 days after each injection were: 2.48, 4.16, and 3.10 (20 mg group); 6.42, 6.62, and 7.12 (40 mg group); and 9.51, 11.7, and 13.0 (60 mg group). At study end, 51% and 57% of patients achieved GH levels ≤2.5 μg/L and
IGF-1 levels below ULN, respectively. Compared with baseline, fasting
blood glucose and HbA1c levels increased, whereas fasting blood
insulin levels decreased.
Acromegaly symptoms were generally improved. Adverse events were mostly gastrointestinal and mild/moderate.
Pasireotide LAR was generally well tolerated. Steady-state PK was achieved after three monthly doses; exposures were approximately dose proportional. Control of GH,
IGF-1, and symptoms improved, suggesting that
pasireotide LAR may be an effective treatment for
acromegaly.