ESPE Abstracts (2018) 89 FC4.6

aGlobal Development, Novo Nordisk A/S, Søborg, Denmark; bNon-Clinical Development, Novo Nordisk A/S, Måløv, Denmark; cGlobal Development – Global Service Center, Novo Nordisk India Private Ltd., Bangalore, India

Background: Somapacitan is a reversible albumin-binding growth hormone (GH) derivative in clinical development for once-weekly administration in patients with GH deficiency (GHD). Clinical data in healthy subjects, and adults and children with GHD showed that once-weekly somapacitan injections were well tolerated with no clinically significant safety or local tolerability issues. A sustained dose-dependent IGF-I response supports a once-weekly treatment regimen.

Objective: The primary objective of this study (NCT02962440) was to investigate absorption, metabolism and excretion in healthy male subjects after a single subcutaneous administration of tritium [3H]-somapacitan. Secondary objectives were to assess the pharmacokinetics (PK) of [3H]-somapacitan and [3H]-somapacitan-related material, and the safety and tolerability of somapacitan, after a single dose of [3H]-somapacitan.

Methods: Subjects (seven healthy males aged 45–62 years, BMI 22.8–27.1 kg/m2) attended up to five clinic visits: visit 1, screening; visit 2, dosing visit (in-clinic stay [16 days]); visits 3 (21 days post-dosing) and 4 (28 days post-dosing), weekly 24-hour in-clinic PK and safety visits; visit 5 (35 days post-dosing), follow-up. Subjects received a single subcutaneous dose of 6 mg somapacitan containing [3H]-somapacitan of 540 μCi/20 MBq at visit 2. Blood, serum, plasma, urine, faeces and expired air were collected for radioactivity assessment.

Results: Twenty-eight days after dosing, 94.0% of the administered dose (range: 90.8–103.5%) was recovered as [3H]-somapacitan-related material, most of which was excreted in urine (80.9%); 12.9% excreted in faeces (both in wet samples) and an insignificant amount (0.19%) in expired air. PK properties of [3H]-somapacitan-related material appeared to be consistent across plasma, serum and blood. Terminal half-life of somapacitan-related material was 189.0, 184.6 and 184.7 hours in plasma, serum and blood (dry samples), respectively. Results from the metabolite analyses will be reported later. Two subjects had six adverse events (AEs); all were mild in severity and considered unlikely to be related to trial product. Both subjects recovered from the AEs.

Conclusion: This is the first study reporting absorption and excretion of somapacitan in human subjects and may be of clinical interest to paediatric endocrinologists treating patients with GHD. 94.0% of [3H]-somapacitan-related material was recovered 28 days after dosing. Urine was the major excretory route, followed by faeces; excretion through expired air was negligible. A single dose of 6 mg somapacitan (containing [3H]-somapacitan [540 μCi/20 MBq]) in healthy male subjects was well tolerated with no safety issues identified.

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