Somapacitan, a once-weekly reversible albumin-binding GH derivative, in children with GH deficiency: A randomized dose-escalation trial.
Clin Endocrinol (Oxf)
; 87(4): 350-358, 2017 Oct.
Article
em En
| MEDLINE
| ID: mdl-28656605
ABSTRACT
OBJECTIVE:
To evaluate the safety, local tolerability, pharmacodynamics and pharmacokinetics of escalating single doses of once-weekly somapacitan, a reversible, albumin-binding GH derivative, vs once-daily GH in children with GH deficiency (GHD).DESIGN:
Phase 1, randomized, open-label, active-controlled, dose-escalation trial (NCT01973244). PATIENTS Thirty-two prepubertal GH-treated children with GHD were sequentially randomized 31 within each of four cohorts to a single dose of somapacitan (0.02, 0.04, 0.08 and 0.16 mg/kg; n=6 each), or once-daily Norditropin® SimpleXx® (0.03 mg/kg; n=2 each) for 7 days. MEASUREMENTS Pharmacokinetic and pharmacodynamic profiles were assessed.RESULTS:
Adverse events were all mild, and there were no apparent treatment-dependent patterns in type or frequency. Four mild transient injection site reactions were reported in three of 24 children treated with somapacitan. No antisomapacitan/anti-human growth hormone (hGH) antibodies were detected. Mean serum concentrations of somapacitan increased in a dose-dependent but nonlinear manner maximum concentration ranged from 21.8 ng/mL (0.02 mg/kg dose) to 458.4 ng/mL (0.16 mg/kg dose). IGF-I and IGFBP-3, and change from baseline in IGF-I standard deviation score (SDS) and IGFBP-3 SDS, increased dose dependently; greatest changes in SDS values were seen for 0.16 mg/kg. IGF-I SDS values were between -2 and +2 SDS, except for peak IGF-I SDS with 0.08 mg/kg somapacitan. Postdosing, IGF-I SDS remained above baseline levels for at least 1 week.CONCLUSIONS:
Single doses of once-weekly somapacitan (0.02-0.16 mg/kg) were well tolerated in children with GHD, with IGF-I profiles supporting a once-weekly treatment profile. No clinically significant safety/tolerability signals or immunogenicity concerns were identified.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hormônio do Crescimento
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Hormônio do Crescimento Humano
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Nanismo Hipofisário
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
Clin Endocrinol (Oxf)
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Eslovênia