title: Pharmacokinetics and pharmacodynamics of figitumumab, a monoclonal antibody targeting the insulin-like growth factor 1 receptor, in healthy participants.
abstract: This study determined the pharmacokinetics (PK) of figitumumab and its effects on insulin-like growth factor (IGF) axis-related biomarkers, following a single intravenous dose (10 [n = 16] and 20 [n = 12] mg/kg) in healthy adults. Serial blood sampling for PK and biomarkers was conducted up to 84 days postdose. A dose increase from 10 to 20 mg/kg led to 1.9- and 2.4-fold increases in mean C(max)  and AUC∞, respectively. Median disposition half-life was 21.1 and 27.8 days at 10 and 20 mg/kg, respectively. At 10 and 20 mg/kg, figitumumab increased total IGF-1, free IGF-1, IGF binding protein (IGFBP)-3, and insulin by 4.1- and 4.8-, 8.3- and 12.1-, 2.4- and 2.9-, and 7.3- and 9.8-fold, respectively; increases were sustained throughout the 84-day period. There was a slight and transient elevation in IGF-2. Mean plasma glucose increased by 18% and 16% at 10 and 20 mg/kg, respectively. Most treatment-related adverse events were mild in severity; the most common included dry eye (n = 9) and ocular hyperemia (n = 9) in the 20-mg/kg group. No antidrug antibodies were detected. Overall, figitumumab (10 or 20 mg/kg) demonstrated PK properties typical of IgG2 antibodies and produced substantial and sustained increases in IGF-1 (total and free), IGFBP-3, and insulin.
authors: Oncology Business Unit, Pfizer, Inc, Groton, CT, USA. donghua.yin@pfizer.com
authors: Donghua
authors: D
authors: Yin
authors: Barbara
authors: B
authors: Sleight
authors: Christine
authors: C
authors: Alvey
authors: Arne G
authors: AG
authors: Hansson
authors: Akintunde
authors: A
authors: Bello
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D008297:Male; D008875:Middle Aged; D017526:Receptor, IGF Type 1 / Q000276:immunology*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D001786:Blood Glucose; C515497:IGFBP3 protein, human; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; C525021:figitumumab