title: Reversible Albumin-Binding GH Possesses a Potential Once-Weekly Treatment Profile in Adult Growth Hormone Deficiency.
abstract: BACKGROUND
  NNC0195-0092 is a reversible, albumin-binding GH derivative, developed for once-weekly administration.
  
  
  OBJECTIVE
  The objective of the study was to evaluate safety, local tolerability, pharmacodynamics, and pharmacokinetics of multiple, once-weekly doses of NNC0195-0092, compared with daily GH.
  
  
  METHODS
  This was a phase 1, randomized, open-label, active-controlled, multiple-dose, dose-escalation trial.
  
  
  METHODS
  Thirty-four GH-treated adult subjects (male, n = 25) with GH deficiency participated in the study.
  
  
  METHODS
  Subjects were sequentially assigned into four cohorts of eight subjects, randomized within each cohort (3:1) to once-weekly NNC0195-0092 (n = 6) for 4 weeks (0.02, 0.04, 0.08, and 0.12 mg/kg) or daily injections of Norditropin NordiFlex (n = 2) for 4 weeks with a dose replicating the pretrial dose of somatropin. A safety assessment was performed prior to initiating treatment at the next dose level of NNC0195-0092. Daily GH treatment was discontinued 14 days before the trial start. Blood samples were drawn for assessment of safety, pharmacokinetics, pharmacodynamics (IGF-1 and IGF-binding protein-3) profiles, and immunogenicity studies.
  
  
  RESULTS
  Numbers of adverse events were similar at the dose levels of 0.02, 0.04, and 0.08 mg/kg NNC0195-0092 vs daily injections of Norditropin NordiFlex, whereas the number of adverse events was greater at the highest dose level of NNC0195-0092 (0.12 mg/kg). NNC0195-0092 (area under the curve[0-168h]) and peak plasma concentration) increased in a dose-dependent manner, and a dose-dependent increase in IGF-1 levels was observed. IGF-1 profiles were elevated for at least 1 week, and for the 0.02-mg/kg and 0.04-mg/kg NNC0195-0092 doses, the observed IGF-1 levels were similar to the levels for the active control group.
  
  
  CONCLUSIONS
  Four once-weekly doses of NNC0195-0092 (dose range 0.02-0.12 mg/kg) administered to adult patients with GH deficiency were well tolerated, and IGF-1 profiles were consistent with a once-weekly treatment profile. No clinically significant safety and tolerability signals causally related to NNC0195-0092 were identified, nor were any immunogenicity concerns revealed.
authors.affiliation: Department of Global Development (M.H.R., L.F.N.), Novo Nordisk, DK-2860 Søborg Denmark; Medical Department of Diabetes and Endocrinology, Aarhus University Hospital (J.J., J.S.C.), DK-8000 C Aarhus, Denmark; Department of Endocrinology, Rigshospitalet, (M.K., D.M., U.F.-R.), University of Copenhagen, DK-2100 Copenhagen, Denmark; Department of Endocrinology, Odense University Hospital (M.T., M.A.), DK-5000 Odense, Denmark; and Department of Endocrinology, Karolinska University Hospital (C.H.), SE-171 76 Stockholm, Sweden.
authors.forename: Michael Højby
authors.initials: MH
authors.lastname: Rasmussen
authors.affiliation: Department of Global Development (M.H.R., L.F.N.), Novo Nordisk, DK-2860 Søborg Denmark; Medical Department of Diabetes and Endocrinology, Aarhus University Hospital (J.J., J.S.C.), DK-8000 C Aarhus, Denmark; Department of Endocrinology, Rigshospitalet, (M.K., D.M., U.F.-R.), University of Copenhagen, DK-2100 Copenhagen, Denmark; Department of Endocrinology, Odense University Hospital (M.T., M.A.), DK-5000 Odense, Denmark; and Department of Endocrinology, Karolinska University Hospital (C.H.), SE-171 76 Stockholm, Sweden.
authors.forename: Jurgita
authors.initials: J
authors.lastname: Janukonyté
authors.affiliation: Department of Global Development (M.H.R., L.F.N.), Novo Nordisk, DK-2860 Søborg Denmark; Medical Department of Diabetes and Endocrinology, Aarhus University Hospital (J.J., J.S.C.), DK-8000 C Aarhus, Denmark; Department of Endocrinology, Rigshospitalet, (M.K., D.M., U.F.-R.), University of Copenhagen, DK-2100 Copenhagen, Denmark; Department of Endocrinology, Odense University Hospital (M.T., M.A.), DK-5000 Odense, Denmark; and Department of Endocrinology, Karolinska University Hospital (C.H.), SE-171 76 Stockholm, Sweden.
authors.forename: Marianne
authors.initials: M
authors.lastname: Klose
authors.affiliation: Department of Global Development (M.H.R., L.F.N.), Novo Nordisk, DK-2860 Søborg Denmark; Medical Department of Diabetes and Endocrinology, Aarhus University Hospital (J.J., J.S.C.), DK-8000 C Aarhus, Denmark; Department of Endocrinology, Rigshospitalet, (M.K., D.M., U.F.-R.), University of Copenhagen, DK-2100 Copenhagen, Denmark; Department of Endocrinology, Odense University Hospital (M.T., M.A.), DK-5000 Odense, Denmark; and Department of Endocrinology, Karolinska University Hospital (C.H.), SE-171 76 Stockholm, Sweden.
authors.forename: Djordje
authors.initials: D
authors.lastname: Marina
authors.affiliation: Department of Global Development (M.H.R., L.F.N.), Novo Nordisk, DK-2860 Søborg Denmark; Medical Department of Diabetes and Endocrinology, Aarhus University Hospital (J.J., J.S.C.), DK-8000 C Aarhus, Denmark; Department of Endocrinology, Rigshospitalet, (M.K., D.M., U.F.-R.), University of Copenhagen, DK-2100 Copenhagen, Denmark; Department of Endocrinology, Odense University Hospital (M.T., M.A.), DK-5000 Odense, Denmark; and Department of Endocrinology, Karolinska University Hospital (C.H.), SE-171 76 Stockholm, Sweden.
authors.forename: Mette
authors.initials: M
authors.lastname: Tanvig
authors.affiliation: Department of Global Development (M.H.R., L.F.N.), Novo Nordisk, DK-2860 Søborg Denmark; Medical Department of Diabetes and Endocrinology, Aarhus University Hospital (J.J., J.S.C.), DK-8000 C Aarhus, Denmark; Department of Endocrinology, Rigshospitalet, (M.K., D.M., U.F.-R.), University of Copenhagen, DK-2100 Copenhagen, Denmark; Department of Endocrinology, Odense University Hospital (M.T., M.A.), DK-5000 Odense, Denmark; and Department of Endocrinology, Karolinska University Hospital (C.H.), SE-171 76 Stockholm, Sweden.
authors.forename: Lene F
authors.initials: LF
authors.lastname: Nielsen
authors.affiliation: Department of Global Development (M.H.R., L.F.N.), Novo Nordisk, DK-2860 Søborg Denmark; Medical Department of Diabetes and Endocrinology, Aarhus University Hospital (J.J., J.S.C.), DK-8000 C Aarhus, Denmark; Department of Endocrinology, Rigshospitalet, (M.K., D.M., U.F.-R.), University of Copenhagen, DK-2100 Copenhagen, Denmark; Department of Endocrinology, Odense University Hospital (M.T., M.A.), DK-5000 Odense, Denmark; and Department of Endocrinology, Karolinska University Hospital (C.H.), SE-171 76 Stockholm, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Höybye
authors.affiliation: Department of Global Development (M.H.R., L.F.N.), Novo Nordisk, DK-2860 Søborg Denmark; Medical Department of Diabetes and Endocrinology, Aarhus University Hospital (J.J., J.S.C.), DK-8000 C Aarhus, Denmark; Department of Endocrinology, Rigshospitalet, (M.K., D.M., U.F.-R.), University of Copenhagen, DK-2100 Copenhagen, Denmark; Department of Endocrinology, Odense University Hospital (M.T., M.A.), DK-5000 Odense, Denmark; and Department of Endocrinology, Karolinska University Hospital (C.H.), SE-171 76 Stockholm, Sweden.
authors.forename: Marianne
authors.initials: M
authors.lastname: Andersen
authors.affiliation: Department of Global Development (M.H.R., L.F.N.), Novo Nordisk, DK-2860 Søborg Denmark; Medical Department of Diabetes and Endocrinology, Aarhus University Hospital (J.J., J.S.C.), DK-8000 C Aarhus, Denmark; Department of Endocrinology, Rigshospitalet, (M.K., D.M., U.F.-R.), University of Copenhagen, DK-2100 Copenhagen, Denmark; Department of Endocrinology, Odense University Hospital (M.T., M.A.), DK-5000 Odense, Denmark; and Department of Endocrinology, Karolinska University Hospital (C.H.), SE-171 76 Stockholm, Sweden.
authors.forename: Ulla
authors.initials: U
authors.lastname: Feldt-Rasmussen
authors.affiliation: Department of Global Development (M.H.R., L.F.N.), Novo Nordisk, DK-2860 Søborg Denmark; Medical Department of Diabetes and Endocrinology, Aarhus University Hospital (J.J., J.S.C.), DK-8000 C Aarhus, Denmark; Department of Endocrinology, Rigshospitalet, (M.K., D.M., U.F.-R.), University of Copenhagen, DK-2100 Copenhagen, Denmark; Department of Endocrinology, Odense University Hospital (M.T., M.A.), DK-5000 Odense, Denmark; and Department of Endocrinology, Karolinska University Hospital (C.H.), SE-171 76 Stockholm, Sweden.
authors.forename: Jens Sandahl
authors.initials: JS
authors.lastname: Christiansen
mesh_terms: D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000172:deficiency* / Q000493:pharmacokinetics; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I; D055666:Lipopeptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D055666:Lipopeptides; C000594654:NNC0195-0092; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I