Comparison of the Pharmacokinetics, Safety and Tolerability of Two Concentrations of a New Liquid Recombinant Human Growth Hormone Formulation versus the Freeze-dried Formulation

Bernd Liedert; Ulf Forssmann; Peter Wolna; Michaela Golob; Andreas Kovar

Disclosures

BMC Clin Pharmacol. 2010;10(14):1-7. 

In This Article

Background

Recombinant human growth hormone (r-hGH) is used for the treatment of children with growth failure due to inadequate secretion of endogenous GH, gonadal dysgenesis (Turner syndrome) or chronic kidney disease, and for short children born small for gestational age. It is also indicated for the treatment of GH deficiency (GHD) in adults. Long-term treatment is effective at promoting growth in GH-deficient children.[1–7] In a retrospective survey of 631 children, r-hGH increased height by a mean of approximately 8 cm per year over 2 years.[3] Similarly, in an open-label study of 69 children with organic or idiopathic GHD, r-hGH was associated with a median growth of 47.5 ± 8.5 cm over 7 years of treatment, with most subjects reaching their predicted final height.[1]

Saizen® (Merck Serono S.A. - Geneva, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany) r-hGH is available as a freeze-dried (FD) multi-dose formulation that needs to be reconstituted with bacteriostatic water before use. Once reconstituted, it is administered from a multi-dose cartridge, either by needle and syringe or by needle-free jet injection. To eliminate this need for reconstitution, a ready-to-use liquid multi-dose formulation is in development, which will avoid any risk of contamination or dilution errors during preparation and increase the convenience of drug administration. Furthermore, increasing the ease of injecting r-hGH may help to improve adherence rates (although this has yet to be demonstrated directly). Non-adherence is a problem with all long-term treatments, and for children taking r-hGH manifests as a lower growth rate in poorly compliant children compared with children who miss fewer injections.[3,8]

The new liquid formulation is being developed in two concentrations: 5.83 and 8.0 mg/mL. This trial is the first comparison of the pharmacokinetics (PK), safety and tolerability of the two concentrations against the FD formulation in healthy volunteers.

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