Population Pharmacokinetic Analysis of an Octreotide Depot (CAM2029) in the Treatment of Acromegaly.

Abstract

Introduction: Octreotide is a first-generation somatostatin receptor ligand (SRL) approved for acromegaly treatment. CAM2029 is a sustained-release subcutaneous octreotide injection designed to improve treatment convenience for patients and bioavailability over alternative SRL treatments. The aim of this analysis was to characterise the pharmacokinetic (PK) properties of CAM2029.

Methods: Using nonlinear mixed-effects modelling, 4098 observations from three trials, including 216 healthy participants and participants with acromegaly, were used to develop a population PK model of octreotide after administration of CAM2029 or immediate-release (IR) octreotide. Simulated octreotide plasma concentration profiles after administration of clinically justified dosing regimens of CAM2029 and octreotide IR were compared.

Results: Octreotide disposition was best described by a two-compartmental distribution with a first-order elimination model. The rapid initial and slow subsequent drug release of CAM2029 was best characterised by two simultaneous first-order absorption processes, whereas octreotide IR absorption was described by a single first-order pathway. The model was qualified to describe octreotide concentrations and supported the robustness of dosing CAM2029 every 4 weeks (Q4W) ± 1 week. Simulations indicated that the average concentration during a dosing interval at steady state for 20 mg CAM2029 Q4W was similar to 0.25 mg octreotide IR every 8 h, but with reduced daily fluctuation.

Conclusions: This population PK model supports the use of CAM2029 as a potential alternative treatment option to both octreotide IR and long-acting repeatable (LAR) for acromegaly treatment. The octreotide bioavailability for CAM2029 was similar to octreotide IR and approximately 5 to 6 fold higher than octreotide LAR, with a more rapid onset.

Trial registrations: 2020-002643-35 (EudraCT), NCT04076462 (date of registration: 3rd September 2019), NCT04125836 (date of registration: 14th October 2019).