Objective: To evaluate the pharmacokinetics, efficacy, and safety of a subcutaneous octreotide hydrogel implant in patients with acromegaly.
Methods: In 2 phase II open-label randomized studies, patients aged ≥ 18 years with confirmed acromegaly and octreotide responsiveness received one or two 52 mg hydrated implants (52 mg study) or a hydrated or nonhydrated 84 mg implant (84 mg study) inserted subcutaneously in the upper arm. Implants were removed after 6 months. The 84 mg study assessed pharmacokinetics in patients with undetectable baseline octreotide concentrations. Both studies assessed efficacy (serum growth hormone [GH], insulin-like growth factor 1 [IGF-1]) and safety (adverse events, physical examination, clinical chemistry).
Results: Eleven patients received 1 (n = 5) or 2 (n = 6) 52 mg implants; 34 received a hydrated (n = 17 [safety]; n = 16 [efficacy analysis]) or nonhydrated (n = 17) 84 mg implant. With the nonhydrated versus hydrated 84 mg implant, mean maximum serum concentration (Cmax) and mean area under the drug concentration versus time curve from time 0 to 6 months were decreased (P = 0.002 and P = 0.03, respectively) and mean time to Cmax was increased (P = 0.002). In both studies, IGF-1 and GH declined in month 1 and were significantly suppressed during the 6-month treatment versus baseline (P<0.001). With the 52 mg and 84 mg implants, respectively, 3 of 11 patients (27%) and 17 of 33 patients (52%) achieved IGF-1 normalization and 8 of 11 patients (73%) and 13 of 33 patients (39%) exhibited GH <2.5 ng/mL; 9 of 11 patients (82%) and 11 of 34 patients (32%) experienced treatment-related adverse events, which were mainly gastrointestinal.
Conclusion: Octreotide hydrogel implants were well tolerated and maintained stable octreotide release and suppression of IGF-1 and GH over 6 months.