Efficacy and safety of eltrombopag in Japanese patients with chronic liver disease and thrombocytopenia: a randomized, open-label, phase II study
Eltrombopag is an oral thrombopoietin receptor agonist that stimulates thrombopoiesis and shows higher exposure in East Asian patients than in non-Asian patients. We evaluated the pharmacokinetics, efficacy, and safety of eltrombopag in Japanese patients with thrombocytopenia associated with chronic liver disease (CLD).
Thirty-eight patients with CLD and thrombocytopenia (platelets <50,000/μL) were enrolled in this phase II, open-label, dose-ranging study that consisted of 2 parts. In the first part, 12 patients received 12.5 mg of eltrombopag once daily for 2 weeks. After the evaluation of safety, 26 patients were randomly assigned to receive either 25 or 37.5 mg of eltrombopag once daily for 2 weeks in the second part.
Pharmacokinetics showed that the geometric means of the maximum plasma concentration (C max) and the area under the curve (AUC) in the 12.5 mg group were 3,413 ng/mL and 65,236 ng h/mL, respectively. At week 2, the mean increases from baseline in platelet counts were 24,800, 54,000, and 60,000/μL in the 12.5, 25, and 37.5 mg groups, respectively. The median platelet counts increased within 2 weeks of the beginning of administration in all groups, and remained at the same level throughout the 2-week post-treatment period in the 12.5 mg group, whereas the platelet counts peaked a week after the last treatment in both the 25 and 37.5 mg groups. Most adverse events reported were grade 1 or 2; 2 patients in the 37.5 mg group had drug-related serious adverse events.
Eltrombopag ameliorated thrombocytopenia in Japanese patients with CLD and thrombocytopenia. The recommended dose for these patients is 25 mg daily for 2 weeks.
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- Efficacy and safety of eltrombopag in Japanese patients with chronic liver disease and thrombocytopenia: a randomized, open-label, phase II study
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Journal of Gastroenterology
Volume 47, Issue 12 , pp 1342-1351
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- Springer Japan
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- Thrombopoietin receptor agonist
- Invasive procedures
- Inter-ethnic difference
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- Author Affiliations
- 2. Department of Digestive Disease Information & Research, and Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan
- 3. Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan
- 4. Department of Internal Medicine 1, Faculty of Medicine, Oita University, Oita, Japan
- 5. Department of Gastroenterology and Hepatology, NTT West Kyushu Hospital, Kumamoto, Japan
- 6. Hepatology Division, Fukuoka Red Cross Hospital, Fukuoka, Japan
- 7. Department of Gastroenterology and Medicine, Kurume University Medical Center, Fukuoka, Japan
- 8. Department of Gastroenterology and Medicine, Fukuoka University School of Medicine, Fukuoka, Japan
- 9. Department of Gastroenterology, Clinical Research Center, Kyushu Medical Center, National Hospital Organization, Fukuoka, Japan
- 10. Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences Kumamoto University, Kumamoto, Japan
- 11. Department of Digestive and Lifestyle-Related Diseases, Health Research Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
- 12. GlaxoSmithKline, Tokyo, Japan