THU073 Somapacitan Administered Subcutaneously At 5 mg/1.5 mL Or 10 mg/1.5 mL Strengths Yields Clinically Similar PK And IGF-I Profiles In Healthy Participants

Abstract

Disclosure: M. Højby Rasmussen: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. R.J. Kildemoes: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. C. Sværke: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk.

Background: Somapacitan is a once-weekly long-acting GH for treatment of AGHD. Objectives: To confirm bioequivalence of sc somapacitan 5 mg/1.5 mL and 10 mg/1.5 mL strengths in equimolar doses of 0.04 mg/kg body weight and investigate pharmacokinetic/pharmacodynamic (PK/PD) properties of the two strengths. Methods: A randomized, double-blind, single-dose, three-period crossover trial. US Food and Drug Administration (FDA) and European Medicines Agency (EMA) bioequivalence guidelines require area under the curve (AUC _0-t) and maximum serum concentration (C _max) to be identical within predefined limits. The 10 mg/1.5 mL strength (reference treatment) was administered in two separate treatment periods. Healthy participants (full analysis set n=32; 5 females; 31 White, 1 Black; mean age 35.1 years; mean BMI 22.8 kg/m ²) were randomized to receive treatment in one of three sequences. Each participant attended three in-house 5-day dosing and PK/PD sampling visits, each followed by daily PK/PD sampling visits for 3 days after each dosing visit and again 1 week later, and finally an end-of-trial visit. Dosing visits were separated by 3 weeks’ washout. Results: For AUC _0-t, treatment ratio (5 mg/1.5 mL vs 10 mg/1.5 mL) was 0.95 [90% CI 0.89;1.01]. Point estimate and 90% CIs were within the acceptance range [0.80;1.25]; bioequivalence criterion for AUC was met. For C _max, treatment ratio was 0.77 [0.68;0.89]. Point estimate was outside [0.80;1.25] and the 90% CI was outside the widened acceptance range [0.70;1.43], defined in line with the EMA guideline on bioequivalence due to within-subject variability of C _max; EMA and FDA bioequivalence criteria for C _max were not met. Treatment ratios of AUC _{0-168 h} and AUC _0-∞ were 0.93 [0.84;1.02] and 0.95 [0.89;1.01], respectively. Geometric mean value of t _½ was comparable for somapacitan 5 mg/1.5 mL (52.7 hours) and reference treatment periods (53.9 and 50.5 hours). Median t _max values were 10 hours (5 mg/1.5 mL) and 8 hours (both reference treatment periods). Mean IGF-I and IGF-I standard deviation score (SDS) concentration-time curves for the two strengths were almost identical. Treatment ratio of AUC _{IGF-I, 0-168 h} was 1.00 [90% CI 0.98;1.02]. Median t _{max, IGF-I} values for the two strengths were identical. Geometric mean value of C _{max, IGF-I} for 5 mg/1.5 mL was similar to that for somapacitan 10 mg/1.5 mL. The two somapacitan strengths showed similar safety profiles, with no new safety issues identified. Conclusion: Bioequivalence criterion for somapacitan 5 mg/1.5 mL and 10 mg/1.5 mL was met for AUC _0-t but not for C _max. Treatment ratios of AUC _{0-168 h} and AUC _0-∞ were similar to those of AUC _0-t. Concentration-time curves of IGF-I and IGF-I SDS for the two strengths were almost identical. Observed difference in C _max was not considered clinically significant; 5 mg/1.5 mL and 10 mg/1.5 mL were equivalent from a clinical perspective, and have been approved by authorities.

Presentation: Thursday, June 15, 2023