An Open-Label, Randomized, Single-Dose, Crossover, Comparative Pharmacokinetics Study of YLB113 and the Etanercept Reference Product in Healthy Adult Male Subjects

Background and Objectives YLB113 is being developed as a biosimilar of the antitumor necrosis factor-alpha antagonist etanercept, which is approved for the treatment of moderate-to-severe rheumatoid arthritis (RA) and other chronic immune-mediated inflammatory diseases. An open-label, crossover, pha...

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Published in:	European journal of drug metabolism and pharmacokinetics Vol. 45; no. 4; pp. 467 - 475
Main Authors:	Shennak, Mustafa, Al-Jaouni, Rana, Kshirasagar, Santhosh, Kasibhatta, Ravi Sekhar, Godse, Neelima, Al-Ghazawi, Ahmad, Vittala, Praveen, Bakhle, Dhananjay
Format:	Journal Article
Language:	English
Published:	Cham Springer International Publishing 01-08-2020
Subjects:	Adult Biological Availability Biomedical and Life Sciences Biomedicine Biosimilar Pharmaceuticals - administration & dosage Biosimilar Pharmaceuticals - adverse effects Biosimilar Pharmaceuticals - pharmacokinetics Cross-Over Studies Drug Monitoring Etanercept - administration & dosage Etanercept - adverse effects Etanercept - pharmacokinetics Healthy Volunteers Human Physiology Humans Injections, Subcutaneous Jordan Male Medical Biochemistry Middle Aged Original Original Research Article Pharmaceutical Sciences/Technology Pharmacology/Toxicology Pharmacy Therapeutic Equivalency Tumor Necrosis Factor Inhibitors - administration & dosage Tumor Necrosis Factor Inhibitors - adverse effects Tumor Necrosis Factor Inhibitors - pharmacokinetics Young Adult Jordan
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Summary:	Background and Objectives YLB113 is being developed as a biosimilar of the antitumor necrosis factor-alpha antagonist etanercept, which is approved for the treatment of moderate-to-severe rheumatoid arthritis (RA) and other chronic immune-mediated inflammatory diseases. An open-label, crossover, pharmacokinetic study was conducted to compare the relative bioavailability and safety of YLB113 and the etanercept reference product (RP) Enbrel ® . Methods Healthy male subjects aged 18–50 years were randomized to receive a single subcutaneous dose of YLB113 in one period and the etanercept RP in another period. A washout period of 28 days separated the two treatment periods. Blood samples were collected for pharmacokinetic analysis predose and until 480 h postdose during both periods. Results Overall, 52 subjects were enrolled, including 51 subjects who completed the first period and 43 subjects who completed the second period. The 90% confidence intervals for the least squares means derived from an analysis of the log-transformed pharmacokinetic parameters maximum serum concentration ( C max ), area under the serum concentration–time curve (AUC) from 0 to the last measurable concentration (AUC (0- t ) ) and AUC from 0 to infinity (AUC (0-∞) ) for etanercept were between the limits of 80 and 125%. Thus, YLB113 met the bioequivalence criterion. YLB113 and the etanercept RP were well tolerated, with 24 subjects reporting 53 adverse events, including 42 mild and 11 moderate events. Treatment-emergent adverse events were reported by 14 and 16 subjects following the administration of YLB113 and the etanercept RP, respectively. Conclusions A single dose of YLB113 exhibited pharmacokinetic and safety profiles comparable with those of the etanercept RP in healthy adult male subjects. Therefore, YLB113 and the etanercept RP can be considered bioequivalent. These findings support the continued development of YLB113 for use in patients with RA. Jordan Food & Drug Administration unique trial number 31/Clinical/2018.
ISSN:	0378-7966 2107-0180
DOI:	10.1007/s13318-020-00613-9