Endocrine Abstracts

Introduction: Pegvisomant is indicated for acromegaly. Doses >20 mg are not commercially available, although daily doses up to 30 mg are approved.

Objectives: 1. To estimate the relative bioavailability (relBA) of single-dose pegvisomant s.c. administrations, one injection of 30 mg/ml (1×30) vs two injections of 15 mg/ml (2×15), and 2. To evaluate their pharmacokinetics (PK), safety and tolerability.

Methods: This was a 2-period, single-dose, crossover study in 14 healthy male and female subjects. All subjects received both doses, 1×30 and 2×15, during two treatment periods separated by two weeks. The injection instructions were given in great details and closely followed to reduce variability. Intensive serum samples were collected up to 16 days post injection and were assayed by a validated 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 relative to 2×15 was 123.89% with a 90% CI (112.91–135.93%). The PK parameters are summarized in Table 1. Adjusted for the difference between actual and nominal pegvisomant amounts in both formulations the difference in dose-adjusted AUC reduced to 13%. Different injection solution concentrations and different number of injections might also have a role. 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.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.