Long-acting pegylated human GH in children with GH deficiency: a single-dose, dose-escalation trial investigating safety, tolerability, pharmacokinetics and pharmacodynamics

This study determined the safety, tolerability, pharmacokinetics and pharmacodynamics of escalating single doses of a pegylated GH (NNC126-0083) developed for once-weekly administration, in children with GH deficiency (GHD). The method was thirty children (age 6 and 12 years and weight 16 kg) were randomised to NNC126-0083 or daily GH treatment. The subjects discontinued their daily GH treatment 7-9 days before receiving NNC126-0083 at 0.01, 0.02, 0.04 or 0.06 mg protein/kg or seven once-daily doses of GH at 0.035 mg protein/kg. Results showed that NNC126-0083 was well tolerated, and no short term safety or local tolerability issues were identified. After NNC126-0083 treatment, dose-dependent IGF1 increases were evident for maximum concentration (Cmax), but not area under the curve (AUC0-168 h). Mean values for IGF1 AUC0-168 h/168 h and Cmax were higher for GH than for NNC126-0083, although the difference was not statistically significant for cohort’s 0.06 mg protein/kg. At 0.06 mg protein/kg, the resulting IGF1 response began subsiding at approximately 3 days post-dose. The authors concluded that single doses of long-acting NNC126-0083 were safe and well tolerated in children with GHD. Increased IGF1 levels were observed in all NNC126-0083 dose groups: however, a satisfactory once-weekly IGF1 profile was not reached within the NNC126-0083 dose levels administered.

Authors: de Schepper, Jean; Rasmussen, Michael Hojby; Gucev, Zoran; Eliakim, Alon; Battelino, Tadej. ;Full Source: European Journal of Endocrinology 2011, 165(3), 401-409 (Eng) ;