ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 GP49 | DOI: 10.1530/endoabs.63.GP49

Pharmacokinetics of somapacitan in individuals with renal impairment: an open-label, parallel group, phase 1 study

Birgitte Bentz Damholt, Charlotte Bisgaard, Sarah Louise Dombernowsky & Michael Højby Rasmussen

Novo Nordisk A/S, Søborg, Denmark.

Background: Somapacitan is a reversible albumin-binding growth hormone (GH) derivative developed for once-weekly administration that acts directly or indirectly via insulin-like growth factor I (IGF-I). As renal impairment may affect drug metabolism and excretion, we report data from an open-label, parallel group, phase I trial (NCT03186495) investigating the pharmacokinetic and pharmacodynamic properties, and safety of somapacitan in individuals with varying degrees of impaired renal function or normal renal function classified by glomerular filtration rate (GFR).

Methods: Participants were enrolled in five renal function groups in a planned ratio of 16:8:8:8:8 corresponding to normal renal function, mild renal impairment, moderate renal impairment, severe renal impairment, and requiring haemodialysis treatment, respectively. Participants received a total of three somapacitan administrations (0.08 mg/kg), one per week for 3 weeks.

Results: Forty-four participants were included: normal function, n=15; mild impairment, n=8; moderate impairment, n=8; severe impairment, n=5; requiring haemodialysis, n=8. Reported data are estimated ratios [90% CI]. Compared with the normal function group, steady-state exposure (AUC0–168h) was higher for the severe renal impairment (1.75 [1.00;3.06]) and requiring haemodialysis (1.63 [1.01;2.61]) groups, and similar for the mild (1.25 [0.74;2.11]) and moderate renal impairment (1.27 [0.77;2.07]) groups. Cmax was similar for all groups (mild impairment, 1.31 [0.71;2.39]; moderate impairment, 1.40 [0.79;2.47]; severe impairment, 1.47 [0.77;2.81]; requiring haemodialysis, 1.34 [0.77;2.32]) compared to the normal renal function group. AUCIGF-I,0–168h was increased in the moderate (1.35 [1.09;1.66]) and severe renal impairment (1.40 [1.10;1.78]), and requiring haemodialysis groups (1.24 [1.01;1.52]), versus the normal function group. AUCIGFBP-3,0–168h increased in all renal impairment groups (mild 1.12 [0.99;1.27]; moderate 1.18 [1.06;1.32]; severe 1.36 [1.20;1.55]; requiring haemodialysis 1.53 [1.37;1.70]) versus the normal function group. No unexpected safety signals were reported.

Conclusions: Degree of renal impairment affected steady-state exposure; individuals with severe renal impairment or requiring haemodialysis had significantly higher somapacitan exposure. Increased exposure was likely related to a decreased GFR, indicating that somapacitan, at least in part, is cleared through the kidneys. Increased levels of IGF-I (in the moderate and severe renal impairment, and requiring haemodialysis groups) and IGFBP-3 (in all renal impairment groups) were likely due to increased somapacitan exposure. Patients with severe renal disease or requiring haemodialysis may require lower doses of somapacitan compared to patients with normal renal function, owing to the increased somapacitan exposure. However, as somapacitan is planned to be individually dose-titrated, no specific adjustments to the dosing recommendations are relevant.

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