Multiple doses of pegylated long-acting growth hormone is well tolerated in healthy male volunteers and possesses a potential once-weekly treatment profile - Archive ouverte HAL
Article Dans Une Revue Clinical Endocrinology Année : 2010

Multiple doses of pegylated long-acting growth hormone is well tolerated in healthy male volunteers and possesses a potential once-weekly treatment profile

Lene Jensen
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Thomas William Anderson
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Thomas Klitgaard
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Jesper Madsen
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Résumé

Objective: Recombinant human growth hormone (rhGH) replacement therapy in children and adults currently requires daily subcutaneous injections for several years or lifelong. The current study examined safety, tolerability, pharmacokinetic and pharmacodynamic response parameters after single and multiple doses of a long-acting rhGH preparation (NNC126-0083). Design: Randomized, double-blind, placebo-controlled, multiple-dose, dose-escalating (0.02, 0.04, 0.08 and 0.16 mg protein/kg), sequential dose group trial. Subjects: Forty adult Japanese healthy males (age 20-45 years; BMI: 18.0-27.0 kg/m2). Five groups (n = 8) were randomized to receive multiple doses of NNC126-0083 (n = 6) or placebo (n = 2). Methods: Primary outcome was safety and tolerability of multiple doses of NNC126-0083 compared with placebo. Blood samples for assessment of pharmacokinetics and pharmacodynamics response (IGF-I and IGFBP-3) were taken after multiple ascending doses. Results: NNC126-0083 was well tolerated and not associated with any local injection-site reactions or lipoatrophy. Following administration, NNC126-0083 levels increased rapidly and remained elevated for several days, returning to baseline before each weekly injection. Steady-state pharmacokinetics was achieved after the third dosing. A more than dose-proportional exposure was observed at the highest NNC126-0083 dose (0.16 mg protein/kg). A strong dose-dependent pharmacodynamic response in circulating concentrations of both IGF-I and IGFBP-3 compared with placebo (p < 0.0001) were observed during administration of all doses. Conclusions: Multiple administration of NNC126-0083 in healthy male volunteers indicates that NNC126-0083 has the potential for an efficacious, well-tolerated, once-weekly rhGH compound in the treatment of GH deficiency.

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Dates et versions

hal-00593444 , version 1 (16-05-2011)

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Michael Højby Rasmussen, Lene Jensen, Thomas William Anderson, Thomas Klitgaard, Jesper Madsen. Multiple doses of pegylated long-acting growth hormone is well tolerated in healthy male volunteers and possesses a potential once-weekly treatment profile. Clinical Endocrinology, 2010, 73 (6), pp.769. ⟨10.1111/j.1365-2265.2010.03863.x⟩. ⟨hal-00593444⟩

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