OBJECTIVE:GH replacement therapy currently requires daily injections, which may be inconvenient and distressing for young patients. 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). DESIGN AND METHODS: Thirty children (age ≥6 and ≤12 years, 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 (n=22) or seven once-daily doses of GH at 0.035 mg protein/kg (n=8). RESULTS: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 (C(max)), but not area under the curve (AUC(0)(-)(168 h)). Mean values for IGF1 AUC(0)(-)(168 h)/168 h and C(max) 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 ∼3 days post-dose. CONCLUSION: 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.
RCT Entities:
OBJECTIVE: GH replacement therapy currently requires daily injections, which may be inconvenient and distressing for young patients. 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). DESIGN AND METHODS: Thirty children (age ≥6 and ≤12 years, 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 (n=22) or seven once-daily doses of GH at 0.035 mg protein/kg (n=8). RESULTS: 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 (C(max)), but not area under the curve (AUC(0)(-)(168 h)). Mean values for IGF1 AUC(0)(-)(168 h)/168 h and C(max) 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 ∼3 days post-dose. CONCLUSION: 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: Jeffrey L Cleland; Nathan C Geething; Jerome A Moore; Brian C Rogers; Benjamin J Spink; Chai-Wei Wang; Susan E Alters; Willem P C Stemmer; Volker Schellenberger Journal: J Pharm Sci Date: 2012-06-07 Impact factor: 3.534
Authors: Kevin C J Yuen; Gerard S Conway; Vera Popovic; George R Merriam; Timothy Bailey; Amir H Hamrahian; Beverly M K Biller; Mark Kipnes; Jerome A Moore; Eric Humphriss; George M Bright; Jeffrey L Cleland Journal: J Clin Endocrinol Metab Date: 2013-04-12 Impact factor: 5.958