Pegvisomant bioavailability of single 30mg/mL subcutaneous injection compared to two 15mg/mL subcutaneous injections: A pharmacokinetic, safety and tolerability study

摘要

Objective: The study was conducted to evaluate the pharmacokinetics (PK), relative bioavailability (relBA), safety and tolerability of two single-dose pegvisomant subcutaneous (SC) administrations: one injection of 30. mg/mL (1. ×. 30. mg/mL) versus two injections of two 15. mg/mL (2. ×. 15. mg/mL). Design: This was a 2-period, single-dose, crossover study in 14 healthy male and female subjects. All subjects received both administrations during the two treatment periods separated by a two-week washout. Serum samples were collected intensively up to 360. h post injection and were assayed by a validated enzyme linked immunosorbent assay (ELISA) for pegvisomant. PK parameters including AUC and Cmax were derived by noncompartmental analyses. Mixed effects model was used to obtain bioavailability estimates. Safety and tolerability were assessed by clinical monitoring, including adverse events, laboratory assessments and injection site reactions. Results: All subjects completed the study. The relBA of 1. ×. 30. mg/mL relative to 2. ×. 15. mg/mL was 123.89% with a 90% CI (112.91-135.93%). Adjusted for the difference in actual pegvisomant amounts in both formulations the dose-adjusted relBA reduced to 112.97% with a 90% CI (103.09-123.80%). Single injection with a higher drug concentration in injection solution might have a role in this 13% higher bioavailability for 1. ×. 30. mg/mL administration. Other PK parameters for the two administrations were comparable. No laboratory abnormalities, vital signs, ECG, or injection site reactions of clinical concern were observed in either treatment. Conclusions: Comparable BA, safety and tolerability of the new 30. mg/mL strength to the currently marketed 15. mg/mL strength were established in this study.