Tildrakizumab, a novel anti-IL-23 monoclonal antibody, is unaffected by ethnic variability in Caucasian, Chinese, and Japanese subjects
| Autor: | Ann Horowitz, Christine Xu, Diana Montgomery, Marianne van Vugt, Shirley Glasgow, Joanne Marjason, Anish Mehta, Sauzanne Khalilieh, Anthe S. Zandvliet |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male medicine.medical_specialty Erythema Tildrakizumab Antibodies Monoclonal Humanized Gastroenterology Interleukin-23 White People Young Adult Pharmacokinetics Asian People Psoriasis Internal medicine Medicine Humans Pharmacology (medical) Young adult Pharmacology Dose-Response Relationship Drug business.industry Antibodies Monoclonal medicine.disease Dose–response relationship Tolerability Monoclonal Female medicine.symptom business |
| Zdroj: | International journal of clinical pharmacology and therapeutics. 53(2) |
| ISSN: | 0946-1965 |
| Popis: | Objective To evaluate the effect of ethnicity on the pharmacokinetics (PK) of tildrakizumab, a novel anti-IL-23 monoclonal antibody for the treatment of psoriasis. Materials and methods This was an open-label, 2-part study in healthy adult subjects. In part 1, Japanese subjects and matched Caucasian and Chinese subjects (to Japanese) were assigned to 1 of 3 cohorts and administered tildrakizumab 50, 200, or 400 mg subcutaneously (SC). In part 2, Japanese subjects received tildrakizumab 10 mg/kg IV. Pre- and post-treatment antidrug antibodies were assessed. Safety and tolerability were assessed throughout the study. Results 59 subjects were enrolled; 53 in part 1 and 6 in part 2. Overall geometric mean AUC∞ was 6.15, 6.05, and 6.32 day×μg/mL/mg in Japanese, Caucasian, and Chinese subjects, respectively, after administration of a single SC dose. Bioavailability was ~92%. Six out of 58 evaluable subjects were positive for post-treatment ADA; 2 of these positive subjects had reduced tildrakizumab exposure. Most AEs were mild in intensity and the most frequent treatment-related AEs were injection site hematoma (15%), injection site pain (10%), and injection site erythema (8%). Conclusions The pharmacokinetics of tildrakizumab were similar in Japanese, Caucasian, and Chinese subjects. Tildrakizumab exposure increased proportionally with dose in the range of 50-400 mg. A single SC dose of 50, 200, and 400 mg or a single IV dose of 10 mg/kg was generally well tolerated. |
| Databáze: | OpenAIRE |
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