Model-Based Predictions of IGF-I Support Once-Weekly Dosing of Somapacitan in Children and Adults
Presentation Number: SUN 455
Date of Presentation: April 2nd, 2017
Rasmus Vestergaard Juul*1, Michael Højby Rasmussen2, Henrik Agersø1 and Rune Viig Overgaard2
1Novo Nordisk A/S, Copenhagen, Denmark, 2Novo Nordisk A/S, Søborg, Denmark
Somapacitan is a long-acting growth hormone (GH) intended for once-weekly subcutaneous administration. As for GH, the mechanism of action of somapacitan is either directly or indirectly via insulin-like growth factor I (IGF-I). The pharmacokinetics (PK) and pharmacodynamic (PD) properties are potentially suitable for a once-weekly administration in humans. Somapacitan doses of 0.02–0.24 mg/kg have been investigated after multiple dosing in adults (healthy and with growth hormone deficiency [GHD]) in phase 1 and somapacitan doses of 0.02–0.16 mg/kg have been investigated after single dosing in children with GHD.
In order to predict the PK and IGF-I profiles for multiple doses of somapacitan in children and adults, a PK/PD model was developed based on PK and IGF-I levels from three phase 1 trials. PK were found to be consistent and body-weight dependent, with little or no accumulation in both children and adults, as described by a non-linear PK model. IGF-I increased with higher somapacitan concentrations, with a delay observed between Cmax PK and Cmax IGF-I.
The PK/PD model was based on goodness of fit judged adequate to simulate the expected IGF-I profiles of intermediate dose levels and to support IGF-I guided dose selection of multiple dosing in children with GHD. Descriptive IGF-I exposure–response analysis of single-dose data indicated that the dose range 0.04–0.16 mg/kg in GHD children provided a change in IGF-I that was comparable to 0.03 mg/kg/day Norditropin®, where 0.4 mg/kg was slightly below and 0.16 mg/kg was slightly above that of daily Norditropin®.
Based on the PK/PD relationship of somapacitan in children, a dose of 0.04 mg/kg is expected to provide Cmax IGF-I levels around the average daily human GH (hGH) treatment; 0.08 mg/kg is expected to provide Cavg IGF-I levels around the average daily hGH treatment; and 0.16 mg/kg is expected to provide higher IGF-I levels, with average concentrations not exceeding +2 SDS after a single dose or at steady state. In conclusion, the PK/PD of somapacitan is well characterized in adults and children in GHD in support of once-weekly dosing.
Disclosure: RVJ: Employee, Novo Nordisk. MHR: Employee, Novo Nordisk. HA: Employee, Novo Nordisk. RVO: Employee, Novo Nordisk.