Efficacy and safety of eltrombopag in Japanese patients with chronic liver disease and thrombocytopenia: a randomized, open-label, phase II study.
BACKGROUND
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
Eltrombopag ameliorated thrombocytopenia in Japanese patients with CLD and thrombocytopenia. The recommended dose for these patients is 25 mg daily for 2 weeks.
Department of Digestive Disease Information & Research, and Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.
Takumi
T
Kawaguchi
Atsumasa
A
Komori
Masataka
M
Seike
Shigetoshi
S
Fujiyama
Hiroshi
H
Watanabe
Masatoshi
M
Tanaka
Shotaro
S
Sakisaka
Makoto
M
Nakamuta
Yutaka
Y
Sasaki
Makoto
M
Oketani
Toshihiro
T
Hattori
Koichi
K
Katsura
Michio
M
Sata
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001565:Benzoates / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006401:Hematologic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D019694:Hepatitis B, Chronic / Q000150:complications; D019698:Hepatitis C, Chronic / Q000150:complications; D006801:Humans; D006834:Hydrazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D008107:Liver Diseases / Q000150:complications*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D016896:Treatment Outcome
D001565:Benzoates; D006401:Hematologic Agents; D006834:Hydrazines; D011720:Pyrazoles; C520809:eltrombopag