ESPE Abstracts (2014) 82 P-D-2-1-420

ESPE2014 Poster Category 2 Growth Hormone (13 abstracts)

S.c. Injections of a Reversible Albumin-Binding GH Derivative (NNC0195-0092) in Adult Subjects with GH Deficiency is Well Tolerated

Michael Højby Rasmussen a , Jurgita Janukonyté b , Marianne Klose c , Djordje Marina c , Mette Tanvig d , Lene Nielsen a , Charlotte Höybye e , Marianne Andersen d , Ulla Feldt-Rasmussen c & Jens Christiansen b

1Global Development, Novo Nordisk, Soeborg, Denmark; 2Aarhus University Hospital, Aarhus, Denmark; 3Rigshospitalet University of Copenhagen, Copenhagen, Denmark; 4Odense University Hospita, Odense, Denmark; 5Karolinska University Hospital, Stockholm, Sweden

Background: Recombinant human GH (rhGH) is normally administered as a daily s.c. injection. NNC0195-0092 is a reversible albumin-binding GH derivative developed with the aim of reducing clearance and thereby extending the exposure. It has previously been demonstrated that NNC0195-0092 is well tolerated in healthy subjects with the potential for once weekly administration.

Objective and hypotheses: In this trial NNC0195-0092 was administrated subcutaneously once weekly for 4 weeks to adult subjects with GH deficiency (AGHD). The subjects enrolled into the trial were on GH replacement therapy, either male or female with a BMI between 18.0 and 35.0 kg/m2, age 20–70 years, HbA1c ≤8.0% and not on insulin treatment.

Method: Fourteen days before being randomized the AGHD subjects discontinued their GH replacement therapy. Four escalating doses of NNC0195-0092 were tested; 0.02, 0.04, 0.08, and 0.12 mg/kg per week and in each dose-group 8 AGHD subjects were dosed with a s.c. administration of NNC0195-0092 (n=6) or Norditropin (n=2). At each dose level the safety and tolerability of NNC0195-0092 were evaluated. In addition, after first and fourth dosing at each dose level the pharmacokinetics and pharmacodynamics (IGFI and IGFBP3) was evaluated as well.

Results: Multiple doses of NNC0195-0092 administered s.c. to AGHD subjects were well tolerated at all doses investigated, with no serious safety issues, or clinically significant local tolerability issues identified. No positive test results for anti NNC0195-0092 antibodies or anti hGH antibodies were reported. The reported adverse events (AE’s) were overall similar to AE’s observed in trials with daily hGH treatment and were thus well-known GH AE’s (peripheral oedema, headache, myalgia, and arthralgia).

Conclusion: In conclusion, multiple doses of NNC0195-0092 administered to AGHD patients are well tolerated and NNC0195-0092 may have the potential to serve as an efficacious and safe once-weekly treatment of GHD in children and adults.

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