Pharmacokinetic and Bioequivalence Evaluation of Prolonged-Release Octreotide Acetate Microspheres in Healthy Human Subjects.

Abstract

Somatostatin analogs such as octreotide have been used in the treatment of acromegaly in the past decades, due to their efficacy in relieving symptoms and lowering growth hormone and insulin-like growth factor 1 levels. Herein, the pharmacokinetic (PK) profile and safety of generic (test product) octreotide acetate microspheres and brand name (reference product) octreotide acetate microspheres in healthy volunteers were compared to assess the bioequivalence. Healthy volunteers were randomized 1:1 to receive single doses of the test product and reference product, respectively. Blood samples of each patient were collected at specific time intervals over an 82-day period. Plasma drug concentrations were tested. The PK parameters were analyzed and compared. Analysis of variance on log-transformed primary PK parameters was applied to analyze the bioequivalence between the test and reference product. The bioequivalence margin was 80%-125%. The PK parameters between the 2 groups were numerically similar. All 90% confidence intervals of the geometric mean ratio for the primary PK parameters fell within 80%-125%, confirming the bioequivalence of the 2 drugs. In this study, 172 (73.9%) adverse events, including 1 (0.4%) non-treatment-related serious adverse event in the test group, were reported. The test product is bioequivalent to the reference product with acceptable safety. The octreotide acetate microspheres provided by 2 sponsors are alternative products.