Pediatric research · 2016
Development and verification of a pharmacokinetic model to optimize physiologic replacement of rhIGF-1/rhIGFBP-3 in preterm infants.
Клиническое исследование I фазыКлиническое исследование II фазыСтатьяРандомизированное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Chung Jou-Ku, Hallberg Boubou, Hansen-Pupp Ingrid, Graham Martin A, Fetterly Gerald, Sharma Jyoti, Tocoian Adina, Kreher Nerissa C, Barton Norman, Hellström Ann, Ley David
Аннотация
BACKGROUND: rhIGF-1/rhIGFBP-3 is being investigated for prevention of retinopathy of prematurity in extremely preterm infants.
METHODS: A population pharmacokinetic model was developed using data from phase I/II (Sections A-C) trials of rhIGF-1/rhIGFBP-3 and additional studies in preterm infants to predict optimal dosing to establish/maintain serum IGF-1 within physiological intrauterine levels. In Section D of the phase II study, infants (gestational age (GA) (wk+d) 23+0 to 27+6) were randomized to rhIGF-1/rhIGFBP-3, administered at the model-predicted dose of 250 µg/kg/d continuous i.v. infusion up to postmenstrual age (PMA) 29 wk+6 d or standard of care. An interim pharmacokinetic analysis was performed for the first 10 treated infants to verify dosing.
RESULTS: Serum IGF-1 data were reviewed for 10 treated/9 control infants. Duration of therapy in treated infants ranged 1-34.5 d. At baseline (before infusion and <24 h from birth), mean (SD) IGF-1 was 19.2 (8.0) μg/l (treated) and 15.4 (4.7) μg/l (controls). Mean (SD) IGF-1 increased to 45.9 (19.6) μg/l at 12 h in treated infants, and remained within target levels for all subsequent timepoints. For treated infants, 88.8% of the IGF-1 measurements were within target levels (controls, 11.1%).
CONCLUSION: Through the reported work, we determined appropriate rhIGF-1/rhIGFBP-3 dosing to achieve physiological intrauterine serum IGF-1 levels in extremely preterm infants.
METHODS: A population pharmacokinetic model was developed using data from phase I/II (Sections A-C) trials of rhIGF-1/rhIGFBP-3 and additional studies in preterm infants to predict optimal dosing to establish/maintain serum IGF-1 within physiological intrauterine levels. In Section D of the phase II study, infants (gestational age (GA) (wk+d) 23+0 to 27+6) were randomized to rhIGF-1/rhIGFBP-3, administered at the model-predicted dose of 250 µg/kg/d continuous i.v. infusion up to postmenstrual age (PMA) 29 wk+6 d or standard of care. An interim pharmacokinetic analysis was performed for the first 10 treated infants to verify dosing.
RESULTS: Serum IGF-1 data were reviewed for 10 treated/9 control infants. Duration of therapy in treated infants ranged 1-34.5 d. At baseline (before infusion and <24 h from birth), mean (SD) IGF-1 was 19.2 (8.0) μg/l (treated) and 15.4 (4.7) μg/l (controls). Mean (SD) IGF-1 increased to 45.9 (19.6) μg/l at 12 h in treated infants, and remained within target levels for all subsequent timepoints. For treated infants, 88.8% of the IGF-1 measurements were within target levels (controls, 11.1%).
CONCLUSION: Through the reported work, we determined appropriate rhIGF-1/rhIGFBP-3 dosing to achieve physiological intrauterine serum IGF-1 levels in extremely preterm infants.