Endocrine Abstracts

Background: Octreotide is the most widely used somatostatin analogue; however, the LAR formulation must be reconstituted prior to intramuscular injection. This Phase I study compared the pharmacokinetics and pharmacodynamics of octreotide Fluid Crystal (FC), a ready-to-use depot formulation for s.c. administration, vs octreotide LAR.

Methods: After a single dose of octreotide s.c. 200 μg, healthy adult male/female volunteers were randomized 1 week later to three injections of octreotide FC 30 mg/month (n=14) or octreotide LAR 30 mg/month (n=14). Blood samples for octreotide and IGF1 analyses were collected pre- and post-injection, and at pre-specified time points during the study. Adverse events were recorded.

Results: Octreotide FC exhibited a steady, rapid increase to peak concentrations (C_max) followed by a slow, exponential decrease through day 28. After injection 3 (steady state): mean±S.D. C_max=29.3±7.1 ng/ml, mean±S.D. AUC_28d=3465±608h ng/ml, median (range) t_max=24 (2–24) h. Octreotide LAR exhibited a burst concentration peak and rapid decline to undetectable values, which rebounded by day 7, stabilized from day 10 and finally decreased around day 21. After injection 3 (steady state): mean±S.D. C_max=1.8±0.6–ng/ml, mean±S.D. AUC_28d=733±222h ng/ml, median (range) t_max=1 (0.5–360) h. Relative bioavailability (using AUC_28d) of octreotide FC vs LAR was 487% (90% CI: 411–578). Octreotide FC provided more rapid and greater IGF1 suppression vs octreotide LAR after injection during weeks 1–2, but similar IGF1 levels were seen during weeks 3–4; AUC for IGF1 suppression was similar in both groups. Comparable injection-site and systemic tolerability was seen across both groups.

Conclusions: Octreotide FC provides greater octreotide bioavailability with a more rapid onset and similar duration of effect compared with octreotide LAR in healthy volunteers, and may offer enhanced convenience as medication as it may be supplied in a convenient, prefilled syringe with a thin needle. A Phase III study of octreotide FC in patients with acromegaly is planned.