Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure.

Abstract

BACKGROUND & AIMS:

This is a phase II multicentre study to investigate the efficacy and safety of avatrombopag (E5501), an investigational second-generation thrombopoietin receptor agonist, administered one week prior to elective procedures in patients with thrombocytopenia secondary to cirrhosis.

METHODS:

Adults with cirrhosis and platelet counts ⩾10 to ⩽58×10(9)/L were randomized to placebo or avatrombopag in two sequential cohorts. Cohort A: placebo vs. one of 3 different doses (100mg loading dose followed by 20, 40, or 80 mg/day on days 2-7) of a first-generation avatrombopag formulation. Cohort B: placebo vs. one of 2 different doses (80 mg loading dose followed by 10 mg/day for days 2-7, or 20mg/day for days 2-4) of a second-generation avatrombopag formulation. Primary end point was achievement of a platelet increase of ⩾20×10(9)/L from baseline and >50×10(9)/L at least once during days 4-8.

RESULTS:

A total of 130 patients were randomized: 93 patients (51, cohort A; 42, cohort B) to avatrombopag and 37 (16, cohort A; 21 cohort B) to placebo. The primary end point was achieved by 49.0% of treated patients in cohort A and 47.6% in cohort B compared to 6.3% and 9.5% of controls; a dose response was seen. Each avatrombopag regimen had a higher proportion of responders compared with their respective cohort placebo arms (p<0.01), except for the 100/40 mg group in cohort A (p=0.17). The most common adverse events were nausea, fatigue, and headache. One patient in the (100/80) avatrombopag group, without a Doppler assessment at screening was diagnosed with portal vein thrombosis during post-treatment follow-up.

CONCLUSIONS:

In this study avatrombopag was generally well-tolerated and increased platelet counts in patients with cirrhosis undergoing elective invasive procedures.

• Authors: Norah A Terrault, Tarek Hassanein, Charles D Howell, Shobha Joshi, John Lake, Linda Sher, Hugo Vargas, Joe McIntosh, Shande Tang, Tim M Jenkins
• Journal: Journal of hepatology (J Hepatol) Vol. 61 Issue 6 Pg. 1253-9 (Dec 2014) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 25048952 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• Receptors, Thrombopoietin
• Thiazoles
• Thiophenes
• avatrombopag

Topics

• Blood Platelets (drug effects)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Elective Surgical Procedures
• Fatigue (epidemiology)
• Female
• Headache (epidemiology)
• Humans
• Incidence
• Liver Cirrhosis (complications)
• Male
• Middle Aged
• Nausea (epidemiology)
• Platelet Count
• Receptors, Thrombopoietin (agonists)
• Risk Factors
• Thiazoles (adverse effects, pharmacology, therapeutic use)
• Thiophenes (adverse effects, pharmacology, therapeutic use)
• Thrombocytopenia (drug therapy, etiology)